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《PloS one》2014,9(12)
Background
Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma.Methods
Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma.Results
The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma.Conclusions
Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery. 相似文献4.
Christian Melb?-J?rgensen Nora Ness Sigve Andersen Andrej Valkov Tom D?nnem Samer Al-Saad Yury Kiselev Thomas Berg Yngve Nordby Roy M. Bremnes Lill-Tove Busund Elin Richardsen 《PloS one》2014,9(11)
Aim
microRNAs (miRNAs) are involved in various neoplastic diseases, including prostate cancer (PCs). The aim of this study was to investigate the miRNA profile in PC tissue, to assess their association with clinicopathologic data, and to evaluate the potential of miRNAs as diagnostic and prognostic markers.Materials and Methods
From a cohort of 535 patients submitted to radical prostatectomy (RP), a sample of 30 patients (14 patients with rapid biochemical failure (BF) and 16 patients without BF) with Gleason score 7 were analyzed. A total of 1435 miRNAs were quantified by microarray hybridization, and selected miRNAs with the highest Standard deviation (n = 50) were validated by real-time quantitative PCR (qRT-PCR). In situ hybridization (ISH) was used to evaluate the expression of miR-21.Results
miR-21 was the only miR that was significantly up-regulated in the BF group (p = 0.045) miR-21 was up-regulated in patients with BF compared with non-BF group (p = 0.05). In univariate analyses, high stromal expression of miR-21 had predictive impact on biochemical failure-free survival (BFFS) and clinical failure-free survival (CFFS) (p = 0.006 and p = 0.04, respectively). In the multivariate analysis, high stromal expression of miR-21 expression was found to be an independent prognostic factor for BFFS in patients with Gleason score 6 (HR 2.41, CI 95% 1.06–5.49, p = 0.037).Conclusion
High stromal expression of miR-21 was associated with poor biochemical recurrence-free survival after RP. For patients with Gleason score 6, miR-21 may help predict the risk of future disease progression and thereby help select patients for potential adjuvant treatment or a more stringent follow-up. 相似文献5.
Postoperative Use of the Chemopreventive Vitamin K2 Analog in Patients with Hepatocellular Carcinoma
Jian-Hong Zhong Xin-Shao Mo Bang-De Xiang Wei-Ping Yuan Jin-Fang Jiang Gui-Sheng Xie Le-Qun Li 《PloS one》2013,8(3)
Aim
To evaluate the chemopreventive efficacy of vitamin K2 (VK2) analog in patients with hepatocellular carcinoma (HCC) after curative hepatic resection or local ablation, since a recent randomized control trial (RCT) and systematic review have given contradictory results.Methods
MEDLINE, EMBASE and Cochrane library databases were systematically searched through the end of May 2012. Meta-analysis of RCTs and cohort studies was performed to estimate the effects of the VK2 analog on tumor recurrence rate and overall survival (OS). Risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated.Results
Six RCTs and one cohort study involving a total of 930 patients were included. VK2 analog therapy did not reduce the 1-year recurrence rate, with a pooled RR of 0.67 (95% CI 0.39–1.13, p = 0.13). However, VK2 analog therapy was associated with a significant reduction in the 2- and 3-year tumor recurrence rates, with respective pooled RRs of 0.65 (95% CI 0.51–0.83, p<0.001) and 0.70 (95% CI = 0.58–0.85, p<0.001). The therapy was also associated with a significant improvement in 1-, 2-, and 3-year OS, with respective pooled RRs of 1.03 (95% CI 1.01–1.05, p = 0.02), 1.11 (95% CI 1.03–1.19, p = 0.005) and 1.14 (95% CI 1.02–1.28, p = 0.02). None of the studies reported adverse effects attributable to VK2 analog therapy.Conclusion
The VK2 analog may reduce recurrence rate after 1 year and improve OS in HCC patients as early as 1 year. However, these findings should be considered preliminary since the majority of patients came from an RCT with survival data out to only 1 year. More extensive studies with larger sample sizes and longer follow-up are needed. 相似文献6.
Jiwen Cheng Wanli Wang Yingjun Zhang Xi Liu Muxing Li Zheng Wu Zhengwen Liu Yi Lv Bo Wang 《PloS one》2014,9(1)
Background
Serum lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.Methods
Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.Results
Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45–1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49–2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 2.53, 95% CI: 1.09–5.89, p = 0.03, respectively).Conclusion
The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration. 相似文献7.
Luca Valenti Benedetta Maria Motta Giorgio Soardo Massimo Iavarone Benedetta Donati Angelo Sangiovanni Alessia Carnelutti Paola Dongiovanni Raffaela Rametta Cristina Bertelli Floriana Facchetti Massimo Colombo Silvia Fargion Anna Ludovica Fracanzani 《PloS one》2013,8(10)
Background & Aims
Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival.Methods
we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data.Results
Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5–9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1–3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20–39 vs. 45, 95% c.i. 38–52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32–64 vs. 55, 95% c.i. 43–67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12–2.78).Conclusions
PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival. 相似文献8.
Yu Zong Li Zhu Jiayi Wu Xiaosong Chen Ou Huang Xiaochun Fei Jianrong He Weiguo Chen Yafen Li Kunwei Shen 《PloS one》2014,9(8)
Purpose
Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making.Patients and Methods
A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors.Results
Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016).Conclusion
In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse. 相似文献9.
Giuseppe Cabibbo Marcello Maida Chiara Genco Nicola Alessi Marco Peralta Giuseppe Butera Massimo Galia Giuseppe Brancatelli Claudio Genova Maurizio Raineri Emanuele Orlando Simona Attardo Antonino Giarratano Massimo Midiri Vito Di Marco Antonio Craxì Calogero Cammà 《PloS one》2013,8(7)
Background
Radio-frequency ablation (RFA) has been employed in the treatment of Barcelona Clinic Liver Cancer (BCLC) early stage hepatocellular carcinoma (HCC) as curative treatments.Aim
To assess the effectiveness and the safety of RFA in patients with early HCC and compensated cirrhosis.Methods
A cohort of 151 consecutive patients with early stage HCC (122 Child-Pugh class A and 29 class B patients) treated with RFA were enrolled. Clinical, laboratory and radiological follow-up data were collected from the time of first RFA.A single lesion was observed in 113/151 (74.8%), two lesions in 32/151 (21.2%), and three lesions in 6/151 (4%) of patients.Results
The overall survival rates were 94%, 80%, 64%, 49%, and 41% at 12, 24, 36, 48 and 60 months, respectively. Complete response (CR) at 1 month (p<0.0001) and serum albumin levels (p = 0.0004) were the only variables indipendently linked to survival by multivariate Cox model. By multivariate analysis, tumor size (p = 0.01) is the only variable associated with an increased likehood of CR.The proportion of major complications after treatment was 4%.Conclusions
RFA is safe and effective for managing HCC with cirrhosis, especially for patients with HCC ≤3 cm and higher baseline albumin levels. Complete response after RFA significantly increases survival. 相似文献10.
Lu Zhang Jianjun Han Huiyong Wu Xiaohong Liang Jianxin Zhang Jian Li Li Xie Yinfa Xie Xiugui Sheng Jinming Yu 《PloS one》2014,9(10)
Background
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and it is the second most common cancer-related mortality globally. The prognostic value of high mobility group box 1 (HMGB1) remains controversial. The purpose of this study is to conduct a meta-analysis and literature review to evaluate the association of HMGB1 expression with the prognosis of patients with HCC.Methods
A detailed literature search was made in Medline, Google Scholar and others for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, Hazard Ratio (HR) and mean difference with corresponding confidence intervals (CIs) were calculated and summarized respectively.Results
10 relevant articles were included for this meta-analysis study. HMGB1 mRNA levels in HCC were significantly higher than those in normal (p<0.00001) and para-tumor tissues (p = 0.002) respectively. The protein levels of HMGB1 in HCC were significantly higher than those in para-tumor tissues (p = 0.005). Two studies reported the serum HMGB1 levels in patients with HCC of TNM stages, and indicating significantly different between stage I and II, stage II and III, as well as stage III and IV (two studies showed p<0.01 and p<0.001 respectively). The overall survival (OS) was significantly shorter in HCC patients with high HMGB1 expression compared those with low HMGB1 expression and the pooled HR was 1.31 with 95% CI 1.20–1.44, Z = 5.82, p<0.0001. Two additional studies showed that there were higher serum HMGB1 levels in patients with chronic hepatitis than those in healthy people (p<0.05).Conclusions
The results of this meta-analysis suggest that HMGB1 mRNA and protein tissue levels in the patients with HCC are significantly higher than those in para-tumor and normal liver tissues respectively. Tissue HMGB1 overexpression is a potential biomarker for HCC diagnosis, and it is significantly associated with the prognosis of patients with HCC. 相似文献11.
Jing Chen Wen-Bin Liu Wei-Dong Jia Ge-Liang Xu Jin-Liang Ma Yun Ren Hao Chen Si-Nan Sun Mei Huang Jian-Sheng Li 《PloS one》2014,9(1)
Background
Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear.Methods
We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters.Results
Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC.Conclusions
Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery. 相似文献12.
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Shu-Mei Yan Jian-Jun Tang Chun-Yu Huang Shao-Yan Xi Ma-Yan Huang Jian-Zhong Liang Yuan-Xue Jiang Yu-Hong Li Zhi-Wei Zhou Ingemar Ernberg Qiu-Liang Wu Zi-Ming Du 《PloS one》2013,8(2)
Background
Zinc finger, DHHC-type containing 2 (ZDHHC2), originally named as reduced expression associated with metastasis protein (REAM), has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma.Methodology/Principal Findings
Quantitative Real-Time PCR (qRT-PCR) and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472) of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001) and histological grade (p<0.001). Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001).Conclusions/Significance
Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients. 相似文献14.
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Qing Zhang Xinguo Chen Yunjin Zang Li Zhang Hong Chen Letian Wang Yujian Niu Xiuyun Ren Zhongyang Shen Lei Shang 《PloS one》2012,7(12)
Background
A precise predictive survival model of liver transplantation (LT) with antiviral prophylaxis for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) and cirrhosis has not been established. The aim of our study was to identify predictors of outcome after LT in these patients based on tumor staging systems, antitumor therapy pre-LT, and antiviral prophylaxis in patients considered to be unfit by Milan or UCSF criteria.Methods
From 2002 to 2008, 917 LTs with antiviral prophylaxis were performed on patients with HBV-cirrhosis, and 313 had concurrent HCC.Results
Stratified univariate and multivariate analyses demonstrated that independent predictors for poor survival were tumor size >7.5 cm (P = 0.001), tumor number >1 (P = 0.005), vascular invasion (P = 0.001), pre-LT serum alpha-fetoprotein (AFP) level ≥1000 ng/ml (P = 0.009), and pre-LT aspartate aminotransferase (AST) level ≥120 IU/L (P = 0.044). Pre-LT therapy for HCC was an independent predictor of better survival (P = 0.028). Based on CLIP and TNM tumor staging systems, HCC patients with HBV-cirrhosis who met the following criteria: solitary tumor ≤7.5 cm, or ≤4 multifocal nodules, the largest lesion ≤5 cm and total tumor diameter ≤10 cm, or more nodules with the largest lesion ≤3 cm, and pre-LT serum AFP level <1000 µg/L and AST level <120 IU/L without vascular invasion and lymph node metastasis who were unfit for UCSF, had survival rates of 89% at 5 years. There was a 47% 5-year survival rate for patients with HCC exceeding the revised criteria.Conclusions
The current criteria for LT based on tumor size, number and levels of AFP and AST may be modestly expanded while still preserving excellent survival after LT. The expanded criteria combined with antiviral prophylaxis and pre-LT adjuvant therapy for HCC may be a rational strategy to prolong survival after LT for HCC patients with HBV-associated cirrhosis. 相似文献16.
Giannis Mountzios Ioannis Kostopoulos Vassiliki Kotoula Ioanna Sfakianaki Elena Fountzilas Konstantinos Markou Ilias Karasmanis Sofia Leva Nikolaos Angouridakis Konstantinos Vlachtsis Angelos Nikolaou Ioannis Konstantinidis George Fountzilas 《PloS one》2013,8(1)
Introduction
Prognosis of patients with operable laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The insulin-like growth factor receptor (IGFR) signaling pathway plays a critical role in laryngeal carcinogenesis and progression.Patients and Methods
We identified all patients with localized TNM stage I–III laryngeal cancer managed with potentially curative surgery between 1985 and 2008. Immunohistochemical (IHC) expression of IGF1R-alpha, IGF1R-beta and IGF2R was evaluated using the immunoreactive score (IRS) and mRNA levels of important effectors of the IGFR pathway were assessed, including IGF1R, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MAP2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PIK3CA, PIK3R1) families. Cox-regression models were applied to assess the predictive value of biomarkers on disease-free survival (DFS) and overall survival (OS).Results
Among 289 eligible patients, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive disease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median IRS as the pre-defined cut-off, patients whose tumors had increased IGF1R-alpha cytoplasm or membrane expression experienced marginally shorter DFS and significantly shorter OS compared to those whose tumors had low IGF1R-alpha expression (91.1 vs 106.2 months, p = 0.0538 and 100.3 vs 118.6 months, p = 0.0157, respectively). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0655) and OS (p = 0.0344). In multivariate analysis, IGF1R-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, p<0.0001), subglottic/transglottic localization (HR = 1.756, p = 0.0438) and IGF1R-alpha protein overexpression (HR = 1.475, p = 0.0504).Conclusion
IGF1R-alpha protein overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of the IGF1R-alpha prognostic utility is warranted. 相似文献17.
Yohei Fujita Masato Okamoto Hiroyuki Goda Tomoyuki Tano Koh-ichi Nakashiro Atsuro Sugita Tomonobu Fujita Shigeo Koido Sadamu Homma Yutaka Kawakami Hiroyuki Hamakawa 《PloS one》2014,9(12)
Purpose
We investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).Experimental Design
Fifty OSCC patients who received radical resection of their tumor(s) were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens.Results
We found that disease-free survival (DFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001). The tumor expression of IL-8, i.e., IL-8(T) and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF) were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively), and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS) in all patients. A multivariate analysis revealed that N status, IL-8(T) and CD163(IF) significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T) or CD163(IF) may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10.Conclusions
These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS. 相似文献18.
Meta-Analysis of Microsomal Epoxide Hydrolase Gene Polymorphism and Risk of Hepatocellular Carcinoma
Background
Hepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent.Methods
PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.Results
Eleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04–1.75, p = 0.02), homozygote comparison (OR = 1.65, 95% CI = 1.07–2.54, p = 0.02) and a recessive genetic model (OR = 1.54, 95% CI = 1.21–1.96, p<0.001), while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC.Conclusion
The 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions. 相似文献19.
Rut Tejero Alfons Navarro Marc Campayo Nuria Vi?olas Ramon M. Marrades Anna Cordeiro Marc Ruíz-Martínez Sandra Santasusagna Laureano Molins Josep Ramirez Mariano Monzó 《PloS one》2014,9(7)
Background
Several treatments in non-small cell lung cancer (NSCLC) are histology-dependent, and the need for histology-related markers is increasing. MicroRNAs (miRNAs) are promising molecular markers in multiple cancers and show differences in expression depending on histological subtype. The miRNA family miR-200 has been associated with the regulation of epithelial-mesenchymal (EMT)/mesenchymal-epithelial transition (MET). EMT involves profound phenotypic changes that include the loss of cell-cell adhesion, the loss of cell polarity, and the acquisition of migratory and invasive properties that facilitates metastasis. A dual role for the miR-200 family in the prognosis of several tumors has been related to tumor cell origin. However, the prognostic role and function of miR-200 family in early-stage NSCLC adenocarcinoma and squamous cell carcinoma (SCC) have not been well established.Methods
miRNA expression was determined using TaqMan assays in 155 tumors from resected NSCLC patients. Functional studies were conducted in three NSCLC cell lines: H23, A-549 and HCC-44.Results
High miR-200c expression was associated with shorter overall survival (OS) in the entire cohort (p = 0.024). High miR-200c (p = 0.0004) and miR-141 (p = 0.009) expression correlated with shorter OS in adenocarcinoma – but not in SCC. In the multivariate analysis, a risk score based on miR-141 and miR-200c expression emerged as an independent prognostic factor for OS in the entire cohort (OR, 2.787; p = 0.033) and in adenocarcinoma patients (OR, 10.649; p = 0.002). Functional analyses showed that miR-200c, was related to mesenchymal-epithelial transition (MET) and affected cell migration and E-cadherin levels, while overexpression of miR-141 reduced KLF6 protein levels and produced an increase of secretion of VEGFA in vitro (H23, p = 0.04; A-549, p = 0.03; HCC-44, p = 0.02) and was associated with higher blood microvessel density in patient tumor samples (p<0.001).Conclusion
High miR-141 and miR-200c expression are associated with shorter OS in NSCLC patients with adenocarcinoma through MET and angiogenesis. 相似文献20.
Bente Vilming Elgaaen Ole Kristoffer Olstad Leiv Sandvik Elin ?degaard Torill Sauer Anne Cathrine Staff Kaare M. Gautvik 《PloS one》2012,7(9)