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1.
Clara Bayarri-Lara Francisco G. Ortega Antonio Cueto Ladrón de Guevara Jose L. Puche Javier Ruiz Zafra Diego de Miguel-Pérez Abel Sánchez-Palencia Ramos Carlos Fernando Giraldo-Ospina Juan A. Navajas Gómez Miguel Delgado-Rodriguez Jose A. Lorente María Jose Serrano 《PloS one》2016,11(2)
Background
Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC.Patients and Methods
56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression.Results
51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0–84) preoperatively and 0.66 (range 0–3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p = .008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50–21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091–0.961, p = 0.043) were independent prognostic factors for DFS.Conclusion
CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence. 相似文献2.
Purpose
Nucleolar spindle-associated protein (NuSAP1) is an important mitosis-related protein, and aberrant NuSAP1 expression is associated with abnormal spindles and mitosis. This study investigated the prognostic value of NuSAP1 in breast cancer.Methods
Two sets of tissue microarrays (TMAs) that included samples from 450 breast cancer patients were constructed, of which 250 patients were training set and the other 200 patients were validation set. Immunohistochemical staining was performed to determine the NuSAP1 levels. A Kaplan-Meier analysis was used to estimate the prognostic value of NuSAP1 in breast cancer. A stepwise Cox analysis was performed to construct a risk-prediction model for triple-negative breast cancer (TNBC). All statistical analysis was performed with SPSS software.Results
There were 108 (43.5%) and 88 (44.0%) patients expressed NuSAP1 in the training set and validation set respectively. High levels of NuSAP1 expression were related to poor disease-free survival (DFS) in both training (P = 0.028) and validation (P = 0.006) cohorts, particularly in TNBC. With combination of two cohorts, both NuSAP1 (HR = 4.136, 95% CI: 1.956–8.747, P < 0.001) and BRCA1 (HR = 0.383, 95% CI: 0.160–0.915, P = 0.031) were independent prognostic indicators of DFS in TNBC. A receiver operating characteristic (ROC) analysis revealed that the combination of NuSAP1 and BRCA1 significantly improved the prognostic power compared with the traditional model (0.778 versus 0.612, P < 0.001).Conclusions
Our study confirms the prognostic value of NuSAP1 in breast cancer. The combination of NuSAP1 and BRCA1 could improve the DFS prediction accuracy in TNBC. 相似文献3.
Marcelo Moura Linhares Renato José Affonso Jr Luciano de Souza Viana Sandra Regina Morini Silva Marcos Vinicius Araujo Denadai Silvia Regina Caminada de Toledo Delcio Matos 《PloS one》2015,10(12)
Objective
To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC).Methods
This retrospective study included 114 patients with stage I–IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan-Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association.Results
In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412–7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367–7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573–9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613–49.711], 39.717 [35.471–43.964], 30.197 [24.030–36.327], respectively.Conclusions
Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6 integrins and GS, and also between the ITGA3 integrin and DFS, in patients with colorectal tumours. A risk scoring system based on detected hyperexpression of 0, 1, or 2 markers (e.g., ITGAV and/or ITGA6) was also found to accurately correlate with the GS curves generated for the present cohort. 相似文献4.
Marica Garziera Marcella Montico Ettore Bidoli Simona Scalone Roberto Sorio Giorgio Giorda Emilio Lucia Giuseppe Toffoli 《PloS one》2015,10(10)
Objective
Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated.Methods
A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed.Results
A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.55–2.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.40–0.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.83–2.25), though not significantly and with a moderate heterogeneity.Conclusions
The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53. 相似文献5.
Background
Recent studies have shown that the forkhead box P3 (FOXP3) protein has a prognostic role in breast cancer. However, these results are controversial. Therefore, the aim of this meta-analysis was to clarify the prognostic role of FOXP3 expression in operable breast cancer cases.Methods
Eligible studies describing the use of FOXP3 as a prognostic factor for operable breast cancer cases were identified. Clinicopathological features, disease-free survival (DFS), and overall survival (OS) data were collected from these studies and were analyzed using Stata software.Results
A total of 16 articles containing data from 13,217 breast cancer patients met the inclusion criteria established for this study. The subsequent meta-analysis that was performed showed that high levels of FOXP3 are not significantly associated with DFS and OS with significant heterogeneity. An additional subgroup analysis demonstrated that intratumoral FOXP3+ regulatory T cells (Tregs) were positively correlated with adverse clinicopathological parameters, yet they did not show an association with DFS or OS. For tumor cells, the pooled results revealed that FOXP3 is significantly associated with DFS (HR: 2.55, 95% CI: 1.23–5.30) but is not associated with clinicopathological parameters or OS. We also observed a significant correlation between FOXP3 expression and survival in the estrogen receptor-positive (ER)+ subgroup (HR: 1.83, 95% CI: 1.36–2.47 for DFS, HR: 1.87, 95% CI 1.28–2.73 for OS), in the Asian region (HR: 1.98, 95% CI: 1.56–2.50 for DFS, HR: 1.93, 95% CI: 1.12–3.35 for OS) and using the median as the FOXP3-positive cut-off value (HR: 1.94, 95% CI: 1.57–2.39 for DFS, HR: 2.06; 95% CI: 1.36–3.11 for OS).Conclusion
This meta-analysis indicates that a prognostic role for FOXP3 expression in operable breast cancer cases depends on the FOXP3-positive region, ER status, geographic region and the FOXP3-positive cut-off value. 相似文献6.
Sven-Erik Olofsson Bj?rn Nodin Alexander Gaber Jakob Eberhard Mathias Uhlén Karin Jirstr?m Mats Jerkeman 《PloS one》2015,10(3)
Background
Expression of the RNA-binding motif protein 3 (RBM3) has been shown to correlate with favourable clinicopathological parameters and prognosis in several cancer diseases. The aim of this study was to examine the expression and prognostic ability of RBM3 in patients with testicular non-seminomatous germ cell tumours (NSGCT).Patients and Methods
Immunohistochemical RBM3 expression was analysed in tissue microarrays with tumours from 206 patients. Chi-square test was applied to analyze associations between RBM3 expression and clinicopathological parameters. Kaplan-Meier analysis was used to assess the impact of RBM3 expression on cancer-specific survival (CSS) and failure-free survival (FFS). Cox regression proportional hazards models were used to estimate the relative risk for failure.Results
In the entire cohort, there was a significant association between clinical stage (p=0.044) and RBM3 expression. Weak RBM3 expression correlated with a significantly reduced FFS [79.3% versus 90.4% (p=0.019)] and CSS [87.5% versus 97.3% (p=0.047)]. For patients with metastatic disease (n = 88), significant associations were found between RBM3 expression and IGCCC group (p=0.007). The FFS was significantly inferior for patients with low tumour-specific RBM3 expression [59.3% versus 79.0% (p=0.013)], and this association remained significant in a multivariable model for patients with metastatic disease (HR=3.67; 95% CI 1.14, 11.89).Conclusion
Low RBM3 expression is an independent predictor of treatment failure in metastatic NSGCT, in relation to the prognostic factors included in the International Germ Cell Consensus Classification (IGCCC). These findings suggest that RBM3 may be a potential biomarker for treatment stratification in patients with metastatic non-seminomatous germ cell tumours, and therefore merit further validation. 相似文献7.
Yuji Miyamoto Yoshifumi Baba Yasuo Sakamoto Mayuko Ohuchi Ryuma Tokunaga Junji Kurashige Yukiharu Hiyoshi Shiro Iwagami Naoya Yoshida Masayuki Watanabe Hideo Baba 《PloS one》2015,10(6)
Background
Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).Methods
We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.Results
One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194–3.619; p = 0.010) was independently associated with OS.Conclusions
Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC. 相似文献8.
Kapo Saukkonen Jaana Hagstr?m Harri Mustonen Anne Juuti Stig Nordling Christian Fermér Olle Nilsson Hanna Sepp?nen Caj Haglund 《PloS one》2015,10(6)
Aim of the Study
Podocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.Patients and Materials
With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associa-tions of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher’s exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier anal-ysis and the Cox proportional hazard model.Results
The polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0%) specimens and the monoclonal antibody was highly expressed in 36 (21.8%) cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045) and perineural invasion (p=0.005), and high expression by the mono-clonal antibody with poor differentiation (p=0.033). High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR) = 1.62; 95% confidence interval (CI) 1.12-2.33; p=0.01) and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001). The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%), and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001).Conclusion
We found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value. 相似文献9.
Xiying Shao Yong Guo Xiaohong Xu Yabing Zheng Jiwen Wang Zhanhong Chen Jian Huang Ping Huang Jufen Cai Xiaojia Wang 《PloS one》2015,10(3)
Purpose
Aromatase, encoded by the CYP19 gene, catalyzes the final step of the conversion of androgens to estrogens. Given the critical role of CYP19 in estrogen synthesis, the potential influence of CYP19 rs4646 polymorphism on breast cancer survival, deserves further study.Methods
Genotyping for CYP19 rs4646 variants was performed on 406 Chinese women with stage I–II and operable stage III breast cancer. Associations were evaluated between CYP19 rs4646 genotypes and disease-free survival (DFS).Results
In premenopausal patients, women who are homozygous for the minor allele (AA) have a longer DFS compared with those carrying the major allele (CC or AC) (87 months versus 48.7 months; Hazard ratio (HR) = 0.56, 95 % CI = 0.318-0.985, P = 0.041). These differences were further demonstrated by a multivariate analysis (HR = 0.456, 95 % CI = 0.249-0.836, P = 0.011). Conversely, the same variant (AA) was estimated to be associated with a poorer DFS in postmenopausal women (AA versus AC or CC: 13.7 months versus 56.3 months; HR = 2.758, 95 % CI = 1.432-5.313, P = 0.002). Furthermore, the differences were confirmed by the COX proportional hazards model (HR = 2.983, 95% CI =1.494-5.955, P = 0.002).Conclusions
The present study indicates that CYP19 rs4646 polymorphism is related to DFS in early breast cancer and that the prognosis index of the homozygous for the minor allele (AA) may depend on menopause status. The findings are novel, if confirmed, rs4646 genotypes may provide useful information for routine management in breast cancer. 相似文献10.
Hui Li Lu-Yan Shen Wan-Pu Yan Bin Dong Xiao-Zheng Kang Liang Dai Yong-Bo Yang Hao Fu He-Li Yang Hai-Tao Zhou Chuan Huang Zhen Liang Hong-Chao Xiong Ke-Neng Chen 《PloS one》2015,10(6)
Background
We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism.Methods
Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo.Results
Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341–0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350–0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably.Conclusions
HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC. 相似文献11.
Gun Oh Chong Shin Young Jeong Shin-Hyung Park Yoon Hee Lee Sang-Woo Lee Dae Gy Hong Jae-Chul Kim Yoon Soon Lee Young Lae Cho 《PloS one》2015,10(9)
Objective
This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy.Methods
Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters.Results
The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7.Conclusion
Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer. 相似文献12.
Background
The prognostic value of circulating tumor cells (CTCs) in ovarian cancer has been investigated in previous studies, but the results are controversial. Therefore we performed a meta-analysis to systematically review these data and evaluate the value of CTCs in ovarian cancer.Materials and Methods
A literary search for relevant studies was performed on Embase, Medline and Web of Science databases. Then pooled hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, sensitivity analyses, meta-regression analyses and publication bias were conducted.Results
This meta-analysis is based on 11 publications and comprises a total of 1129 patients. The prognostic value of the CTC status was significant in overall survival (OS) (HR, 1.61;95% CI,1.22–2.13) and progression-free survival (PFS)/disease-free survival (DFS) (HR, 1.44; 95%CI, 1.18–1.75). Furthermore, subgroup analysis revealed that the value of CTC status in OS was significant in "RT-PCR" subgroup (HR, 2.02; 95% CI, 1.34–3.03), whereas it was not significant in "CellSearch" subgroup (HR, 1.15; 95% CI 0.45–2.92) and "other ICC" subgroup (HR, 1.09; 95% CI 0.62–1.90). The presence of CTC was also associated with an increased CA-125 (OR, 4.07; 95%CI, 1.87–8.85).Conclusion
Our study demonstrates that CTC status is associated with OS and PFS/DFS in ovarian cancer. 相似文献13.
Fabien Vidal Paul Guerby Mathieu Luyckx Pascale Haddad Eberhard Stoeckle Philippe Morice Eric Leblanc Fabrice Lecuru Emile Dara? Jean Marc Classe Christophe Pomel Thomas Filleron Gwenael Ferron Denis Querleu Arash Rafii 《PloS one》2016,11(1)
Objective
Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.Study Design
We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis.Results
The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5).Conclusion
ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. 相似文献14.
George Pentheroudakis Georgia Raptou Vassiliki Kotoula Ralph M. Wirtz Eleni Vrettou Vasilios Karavasilis Georgia Gourgioti Chryssa Gakou Konstantinos N. Syrigos Evangelos Bournakis Grigorios Rallis Ioannis Varthalitis Eleni Galani Georgios Lazaridis George Papaxoinis Dimitrios Pectasides Gerasimos Aravantinos Thomas Makatsoris Konstantine T. Kalogeras George Fountzilas 《PloS one》2015,10(5)
Background
Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study.Patients and Methods
Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa.Results
Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC.Conclusions
In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression.Trial Registration
ANZCTR.org.au ACTRN12610000509066 相似文献15.
Background
Male breast cancer (MBC) is known to be rare compared with female breast cancer (FBC) and to account for only 1% of all breast cancers. To date, male patients diagnosed with breast cancer are normally treated based on the guidelines for FBC. Specifically, studies have found that diagnosing and treating MBC patients under the guidelines for the treatment of post-menopausal FBC are more favorable than are those of pre/peri-menopausal FBC from a physiological perspective because MBC and post-menopausal FBC patients show high estrogen receptor (ER) expression in the tumor and low estrogen expression in the body. In this medical study, we aimed to examine whether MBC actually has the same prognosis as post-menopausal FBC.Method
We identified MBC patients who were diagnosed as operable and who completed clinical treatment and we used follow-up data that were collected from January 2001 to January 2011. Each MBC patient was paired with four FBC patients who were diagnosed within the same period (two were pre/peri-menopausal, and two were post-menopausal). We compared disease-free survival (DFS) and overall survival (OS) among three groups, i.e., pre/peri-menopausal FBC (group A), post-menopausal FBC (group B) and MBC (group M), using the Kaplan-Meier method and a Cox proportional hazards regression model. We also evaluated the clinical characteristics of breast cancer patients using t-tests and chi-square tests. We used ten consecutive years of data that were collected at Zhejiang Provincial Cancer Hospital.Results
We identified 91 MBC cases for group M, 182 FBC cases for group A and 182 FBC cases for group B. The median follow-up period was 112 months. MBC cases were much more frequently ER positive than those of group A and group B (p<0.01); a similar trend was also found for progesterone (PR)-positive cases (p<0.01). The MBC group showed much lower human epidermal growth factor receptor-2 (HER2) expression than did the other groups (p<0.01). The 10-year OS rates were 79.1% for group M (72/91), 79.1% (144/182) for group A, and 87.9% (160/182) for group B, log-rank test indicated that group M had similar mean OS time as group A and group B (GourpM vs group A: p = 0.709; group M vs group B: p = 0.042). The Cox proportional hazards regression model indicated that pre/peri-menopausal FBC had similar DFS (hazard ratio (HR) = 0.706, p = 0.262) and OS (HR = 1.029, p = 0.941) values compared with MBC, whereas post-menopausal FBC had higher DFS (HR = 0.454, p = 0.004) and OS (HR = 0.353, p = 0.003) values than did MBC.Conclusion
Based on this study, we can conclude that MBC displayed higher ER- and PR-positive expression and lower HER2-positive expression than both post-menopausal and pre/peri-menopausal FBC. However, the DFS and OS values of MBC were similar to those of pre/peri-menopausal FBC and were worse than were those of post-menopausal FBC. 相似文献16.
Taeryool Koo Changhoon Song Jae-Sung Kim Kyubo Kim Eui Kyu Chie Sung-Bum Kang Keun-Wook Lee Jee Hyun Kim Seung-Yong Jeong Tae-You Kim 《PloS one》2015,10(9)
Purpose
To evaluate the prognostic impact of the lymph node ratio (LNR) in ypStage III rectal cancer patients who were treated with neoadjuvant chemoradiotherapy (NCRT).Materials and Methods
We retrospectively reviewed the data of 638 consecutive patients who underwent NCRT followed by total mesorectal excision, and postoperative adjuvant chemotherapy for rectal cancer from 2004 to 2011. Of these, 125 patients were positive for lymph node (LN) metastasis and were analyzed in this study.Results
The median numbers of examined and metastatic LNs were 17 and 2, respectively, and the median LNR was 0.143 (range, 0.02–1). Median follow-up time was 55 months. In multivariate analyses, LNR was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] 2.17, p = 0.041), disease-free survival (DFS) (HR 2.28, p = 0.005), and distant metastasis-free survival (DMFS) (HR 2.30, p = 0.010). When ypN1 patients were divided into low (low LNR ypN1 group) and high LNR (high LNR ypN1 group) according to a cut-off value of 0.152, the high LNR ypN1 group had poorer OS (p = 0.043) and DFS (p = 0.056) compared with the low LNR ypN1 group. And there were no differences between the high LNR ypN1 group and the ypN2 group in terms of the OS (p = 0.703) and DFS (p = 0.831).Conclusions
For ypN-positive rectal cancer patients, the LNR was a more effective prognostic marker than the ypN stage, circumferential resection margin, or tumor regression grade after NCRT, and could be used to discern the high-risk group among ypN1 patients. 相似文献17.
Nan Song Ji-Yeob Choi Hyuna Sung Sujee Jeon Seokang Chung Minkyo Song Sue K. Park Wonshik Han Jong Won Lee Mi Kyung Kim Keun-Young Yoo Sei-Hyun Ahn Dong-Young Noh Daehee Kang 《PloS one》2015,10(4)
Purpose
It is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival.Methods
Among 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8%) died and 528 patients (15.4%) recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS) were estimated by hazard ratios (HRs) and 95% confidence intervals (95% CIs) using a multivariate Cox proportional hazard model.Results
An older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19), a greater number of children (≥4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26), and a shorter time since last birth (<5 vs. ≥20 years, HR for DFS=1.67, 95% CI=1.07-2.62) were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99). In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+) tumors.Conclusions
It is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype. 相似文献18.
Background
Carcinoembryonic antigen (CEA) is commonly used as a serum tumor marker in clinical practice; however, its prognostic value for gastric cancer patients remains uncertain. This meta-analysis was performed to assess the prognostic value of CEA and investigate CEA as a tumor marker.Methods
PubMed, EMBASE and other databases were searched for potentially eligible studies. Forty-one studies reporting the prognostic effect of pretreatment serum CEA expression in gastric cancer patients were selected. Data on 14651 eligible patients were retrieved for the meta-analysis. Based on the data extracted from the available literature, the hazard ratio (HR) and 95% confidence interval (CI) for an adverse prognosis were estimated for gastric cancer patients with elevated pretreatment serum levels of CEA (CEA+) relative to patients with normal pretreatment CEA levels (CEA-).Results
The CEA+ patients had a significantly poorer prognosis than the CEA- patients in terms of overall survival (OS: HR 1.716, 95% CI 1.594 - 1.848, P< 0.001), disease-specific survival (DSS: HR 1.940, 95% CI 1.563 - 2.408, P< 0.001), and disease-free survival (DFS: HR 2.275, 95% CI 1.836 - 2.818, P< 0.001). Publication bias and an influence of different cut-off values were not observed (all P> 0.05). In the pooled analyses of multivariate-adjusted HRs, the results suggested that pretreatment serum CEA may be an independent prognostic factor in gastric cancer (OS: HR 1.681, 95% CI 1.425 - 1.982; DSS: HR 1.900, 95% CI 1.441 - 2.505; DFS: HR 2.579, 95% CI 1.935 - 3.436).Conclusion/Significance
The meta-analysis based on the available literature supported the association of elevated pretreatment serum CEA levels with a poor prognosis for gastric cancer and a nearly doubled risk of mortality in gastric cancer patients. CEA may be an independent prognostic factor for gastric cancer patients and may aid in determining appropriate treatment which may preferentially benefit the CEA+ patients. 相似文献19.
Background
Prostate cancer (PCa) is the most common cancer among men in western countries. While active surveillance is increasingly utilized, the majority of patients are currently treated with radical prostatectomy. In order to avoid over-treatment, there is an indisputable need for reliable biomarkers to identify the potentially aggressive and lethal cases. Nuclear intermediate filament proteins called lamins play a role in chromatin organization, gene expression and cell stiffness. The expression of lamin A is associated with poor outcome in colorectal cancer but to date the prognostic value of the lamins has not been tested in other solid tumors.Methods
We studied the expression of different lamins with immunohistochemistry in a tissue microarray material of 501 PCa patients undergoing radical prostatectomy and lymph node dissection. Patients were divided into two staining categories (low and high expression). The correlation of lamin expression with clinicopathological variables was tested and the association of lamin status with biochemical recurrence (BCR) and disease specific survival (DSS) was further analyzed.Results
Low expression of lamin A associated with lymph node positivity (p<0.01) but not with other clinicopathological variables and low expression had a borderline independent significant association with DSS (HR = 0.4; 95% CI 0.2–1.0; p = 0.052). Similarly, low lamin C expression associated with poorer survival (HR = 0.2; 95% CI 0.1–0.6; p = 0.004). Lamin B1 expression did not associate with clinicopathological variables but high expression independently predicted BCR in multivariable Cox regression analysis (HR = 1.8; 95% CI 1.1–2.9; p = 0.023). Low expression of lamin B2 correlated with lymph node positivity (p<0.01) and predicted unfavorable DSS (HR = 0.4; 95% CI 0.2–1.0; p = 0.047).Conclusions
These results suggest differential roles for lamins in PCa progression. Reduced amounts of lamin A/C and B2 increase risk for lymph node metastasis and disease specific death possibly through increased nuclear deformability while high expression of lamin B1 predicts disease recurrence. 相似文献20.
Siyang Feng Yuanyuan Wang Kaican Cai Hua Wu Gang Xiong Haofei Wang Ziliang Zhang 《PloS one》2015,10(10)