ARID1A deficiency associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes predicts a good prognosis of endometrial carcinoma

BackgroundARID1A alterations have been detected in 40% of endometrial carcinomas (ECs) and are associated with loss of its expression. The role of ARID1A in tumorigenesis and development is complex, and the prognostic role in EC remains controversial. Hence, it is of great significance to confirm the role of ARID1A in EC.MethodsA total of 549 EC patients (cohort A) from TCGA were evaluated to explore the prognostic role of ARID1A. NGS was performed for 13 EC patients (cohort B), and expression of ARID1A, CD3, CD8 and mismatch repair (MMR) proteins in 52 patients (cohort C) from our center was determined by immunohistochemistry (IHC). The Kaplan–Meier method was used to perform survival analyses.ResultsARID1A alterations were detected in 32% of EC patients and correlated with good disease-free survival (DFS, P = 0.004) and overall survival (OS, P = 0.0353). ARID1A alterations were found to co-occur with MMR-related gene mutations and correlated with higher PD-L1 expression. Patients concomitantly harboring ARID1A alterations and MMR-related gene mutations had the best prognosis (DFS: P = 0.0488; OS: P = 0.0024). A cohort from our center showed that ARID1A deficiency was an independent prognostic factor and predicted longer recurrence-free survival (P = 0.0476). ARID1A loss was associated with a tendency toward MSI-H (P = 0.0060). ARID1A alterations and expression loss were associated with a higher abundance of CD3+ (P = 0.0406) and CD8+ (P = 0.0387) T cells.ConclusionARID1A alterations and expression loss are tightly associated with MMR deficiency and a high abundance of tumor-infiltrating lymphocytes, which might contribute to the good prognosis of EC.     

Impact of Diabetes Mellitus on the Prognosis of Patients with Hepatocellular Carcinoma after Curative Hepatectomy

Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy. Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model. Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS. Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis.     

Clinical significance of risk stratification of esophageal squamous cell carcinoma after neoadjuvant chemoradiation and surgery

ObjectiveNowadays, there were few studies reporting the risk stratification of patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiation (NCRT) and surgery. We aimed to establish a simple risk stratification to help postoperative detection and adjuvant treatment.MethodsWe included 146 patients with locally advanced ESCC who received NCRT followed by esophagectomy. The impacts of clinicopathological factors on overall survival (OS) and disease-free survival (DFS) were analyzed. The recurrence site, time, and frequency were recorded as well.ResultsThe median follow-up was 53 months. The pathological complete respond (pCR) group demonstrated better 5-year OS and DFS (78.6% and 77.0%) than the non-pCR group (44.8% and 35.2%, all P < 0.005). Multivariate analysis for the non-pCR group revealed perineural invasion (PNI) (HR:2.296, P = 0.013) and ypTNM stage (I/II vs III/IV) (HR:1.972, P = 0.046) were considered as independent unfavorable factors affecting OS, while PNI (HR:1.866, P = 0.045) and lymph vessel invasion (LVI) (HR:3.370, P < 0.001) were considered as independent adverse factors for DFS. Based on clinicopathological factors (including pCR, ypTNM stage, PNI, LVI), patients were divided into the low-risk (pCR), mediate-risk (non-pCR without PNI, LVI, stage III/IV), high-risk (non-pCR with one factor of PNI, LVI or stage III/IV (n = 45)), highest risk (non-pCR with two or more factors of PNI, LVI or stage III/IV) groups. The corresponding 5-year OS rates were 78.6%, 60.4%, 49.6%, 18.6%, respectively (P < 0.005) and 5-year DFS rates were 77.0%, 46.9%, 41.1%, 12.1%, respectively (P < 0.005). Adjuvant chemotherapy may improve survival in high or highest risk groups of patients with low prognostic nutritional index (< 49).ConclusionsA novel risk stratification based on clinicopathological factors may be conducive to postoperative surveillance and guide adjuvant chemotherapy.     

Prognostic Significance of Combination of Preoperative Platelet Count and Neutrophil-Lymphocyte Ratio (COP-NLR) in Patients with Non-Small Cell Lung Cancer: Based on a Large Cohort Study

IntroductionThe aim of this study was to investigate the prognostic significance of the combination of the preoperative platelet count and neutrophil-lymphocyte ratio (COP-NLR) for predicting postoperative survival of patients undergoing complete resection for non-small cell lung cancer (NSCLC).MethodsThe preoperative COP-NLR was calculated on the basis of data obtained.Patients with both an increased platelet count (>30.0×10⁴ mm^-3) and an elevated NLR (>2.3) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively.ResultsA total of 1238 NSCLC patients were enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory variables selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to 2.200, P<0.001) and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001). In sub-analyses by tumor stage (I, II, IIIA), a significant association was found between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002, P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS). When the subgroup of patients with high-risk COP-NLR (score of 2) was analyzed, no benefit of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS).ConclusionsThe preoperative COP-NLR is able to predict the prognosis of patients with NSCLC and divide these patients into three independent groups before surgery. Our results also demonstrate that high-risk patients based on the COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted.     

Clinical outcomes of female breast cancer according to BRCA mutation status

BackgroundTo investigate breast cancer prognosis (disease-free (DFS) and overall survival (OS)) among carriers of germline BRCA mutations (BRCAm) in Denmark.MethodsWe identified all women in Central and Northern Denmark diagnosed with breast cancer during 2004–2011. We retrieved information on germline BRCAm testing from Clinical Genetics departments and clinical/treatment characteristics from population-based medical registries. Follow-up for recurrence, new primary cancer, and mortality extended from 180 days after diagnosis until 31/12/2012. We estimated median DFS and OS and five-year cumulative incidence and incidence rates (IR/1000 person-years), and 95% confidence intervals (95% CI), for each outcome.ResultsAmong 9874 patients, 523 (5%) underwent BRCA testing—90 were BRCAm carriers, 433 were BRCA wildtype (BRCAwt). Compared with BRCAwt women, BRCAm carriers were younger, had lower stage, and ER- and HER2- tumors. Median time from diagnosis to BRCA testing was 0.91 years and 1.3 years in BRCAm and BRCAwt women; median follow-up to first event was 3.9 and 3.4 years, respectively. Five-year DFS and OS were higher in BRCAm than BRCAwt women: 88% (95%CI = 78.3–93.5) vs. 75.3% (95%CI = 70.2–79.6) and 97.8% (95%CI = 91.4–99.4) vs 92.2% (95%CI = 88.5–94.7), respectively. Five-year IRs of recurrence were 36.7/1000 person-years (95%CI = 15.8–72.2) in the BRCAm cohort vs. 58.4 (95%CI = 42.9–77.6) in the BRCAwt cohort.ConclusionsBRCAm carriers may have a better prognosis than BRCAwt women. However, limited testing conducted mainly during follow-up, yielded low numbers for precise estimations, and may be attributable to selection bias.     

Preoperative red blood cell distribution width as an independent prognostic factor in metastatic renal cell carcinoma

ObjectiveThis study aimed to explore the prognostic value of preoperative red blood cell distribution width (RDW) in patients with metastatic renal cell carcinoma (mRCC).MethodsClinicopathological data of 230 patients with mRCC treated at the First Affiliated Hospital of Chongqing Medical University and the Chinese PLA General Hospital from January 2008 to December 2018 were retrospectively analyzed. Patients were stratified according to the optimal cut-off value of RDW calculated using X-tile software. The prognostic value of RDW was analyzed using the Kaplan-Meier curve with log-rank test and univariate and multivariate Cox proportional hazards models.ResultsA total of 230 patients were included. The optimal cut-off value of RDW obtained using X-tile software was 13.1%. The median Progression-free survival (PFS) and Overall survival (OS) of all populations were 12.06 months (IQR: 4.73–36.9) and 32.20 months (IQR: 13.73–69.46), respectively. Kaplan–Meier curves showed that patients with high RDW had worse PFS and OS than those with low RDW (median PFS of 9.7 months vs. 17.9 months, P = 0.002, and median OS of 27.8 months vs. 45.1 months, P = 0.012, respectively). Multivariate analysis showed that RDW was an independent risk factor for PFS (HR: 1.505; 95% CI: 1.111–2.037; P = 0.008) and OS (HR: 1.626; 95% CI: 1.164–2.272; P = 0.004) in mRCC after cytoreductive nephrectomy.ConclusionPreoperative RDW was independently associated with PFS and OS in patients with mRCC and may be a potential predictor of survival outcomes in mRCC.     

Tumor Infiltrating Lymphocytes and NHERF1 Impact on Prognosis of Breast Cancer Patients

BACKGROUND: Breast cancer (BC) is a heterogeneous disease, and patients with apparently similar clinicopathological characteristics in clinical practice show different outcome. This study evaluated in primary BCs and in the subgroup of the triple-negative breast cancers (TNBCs) the level of tumor infiltrating lymphocytes (TILs), Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) expression, and their association respect to the clinical outcome of patients. MATERIAL AND METHODS: NHERF1 expression was assessed by immunohistochemistry in 338 BC samples; the analysis of TILs was examined using hematoxylin and eosin stained slides, according to International TILs Working Group 2014. RESULTS: Multivariate analysis identified TILs as an independent prognostic factor for DFS in the entire cohort and in the TNBC subgroup (HR, 0.32; 95% CI, 0.12–0.87; P = 0.026; and HR, 0.22; 95% CI, 0.06–0.80; P = 0.022, respectively). Univariate and survival analysis by Kaplan–Meier method revealed that patients with cytoplasmic (c) NHERF1^-/TILs⁺ expression had better DFS than other patients (P = 0.049), and this result was also found in the TNBC subgroup (P = 0.031). Moreover, TNBC patients with cNHERF1⁻/TILs⁻ expression had a worse DFS and OS than other patients (P = 0.057 and P = 0.002, respectively). CONCLUSIONS: In the complex scenario of BC and in the era of tumor immunogenicity and immunotherapy, we found an association of TIL levels and cNHERF1 expression that could be useful to identify BCs and particularly TNBC patients with different prognosis and clinical outcome.     

The expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.     

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients.MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses.ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%.ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.     

Preoperative neutrophil-to-lymphocyte ratio (preNLR) for the assessment of tumor characteristics in lung adenocarcinoma patients with brain metastasis

ObjectivesBrain metastases from lung adenocarcinoma cause significant patient mortality. This study aims to evaluate the role of preoperative Neutrophil-to-Lymphocyte ratio (preNLR) in predicting the survival and prognosis of Lung adenocarcinoma (LUAD) patients with brain metastasis (BM) and provide more references for predicting peritumoral edema.MethodsWe retrospectively reviewed 125 LUAD-BM patients who had undergone surgical resection from December 2015 to December 2020. The clinical characteristic, demographic, MRI data, and preNLR within 24–48 h before craniotomy were collected. Patients were divided into two groups based on preNLR (high NLR and low NLR), with cutoff values determined by receiver operating characteristic (ROC) analysis. Association between preoperative NLR and clinical features was determined by using Pearson chi-squared tests. Uni- and multivariate analyzes were performed to compare the overall survival (OS) of clinical features.ResultsThe patients were divided into NLR-low (64 patients) and NLR-high (61 patients) groups based on receiver operating characteristic analysis of NLR area. According to correlation analysis, a high preNLR (NLR≥2.8) is associated with the both supra- and infratentorial location involved (P = 0.017) and a greater incidence of severe peritumoral edema (P = 0.038). By multivariable analysis, age ≥ 65 years (P = 0.011), KPS < 70 (P = 0.043), elevated preNLR (P = 0.013), extracerebral metastases (P = 0.003), EGFR/ALK+ (P = 0.037), postoperative radiotherapy (P = 0.017) and targeted therapy (P = 0.007) were independent prognostic factors. OS nomogram was constructed based on cox model and model performance was examined (AUC = 0.935).ConclusionsPreNLR may serve as a prognosis indicator in LUAD patients with brain metastasis, and high preNLR tends to be positively associate with multiple locations and severe peritumoral edema.     

Higher serum sPD-L1 levels after radiotherapy indicate poor outcome in hepatocellular carcinoma patients

BackgroundOur preclinical research reveals that radiotherapy (RT) promoted PD-L1 upregulation in tumor tissues and that higher PD-L1 after RT worsened the prognosis through immunosuppression. We sought to validate our experimental results in clinical cohorts and promote clinical application.Patients and methodsIn cohort 1, formalin-fixed paraffin-embedded samples were obtained from 46 HCC patients, 23 of whom received preoperative RT and the other 23 received direct surgery. A prospectively collected database contained 122 HCC patients treated with liver RT were enrolled in cohort 2. Blood samples were taken a day before and two weeks after RT. Patients in cohort 2 were further divided into two groups, exploration (73 patients) and validation (49 patients) groups.ResultsIn cohort 1, RT increased the expression of PD-L1 in tumor tissues (p = 0.001), and PD-L1 levels were associated with decreased cytotoxic T-cell infiltration and a trend toward poor prognosis (p = 0.14). Moreover, PD-L1 expression in tumor tissue positively correlated with soluble (s) PD-L1 in serum (R = 0.421, p = 0.046). Then, in cohort 2, we revealed RT increased sPD-L1 in serum (p < 0.001), which was associated with the number of circulating CD8+ T cells (R = -0.24, p = 0.036), indicating poor survival. Furthermore, patients with higher rate of sPD-L1 increase after RT have better treatment response (p < 0.001), PFS (p = 0.032) and OS (p = 0.045).ConclusionHigher post-RT serum sPD-L1, which may potentiate immune suppression effects, indicates a poor prognosis for HCC patients treated with RT.     

A panel of differentially methylated regions enable prognosis prediction for colorectal cancer

We aim to identify a panel of differentially methylated regions (DMRs) for predicting survival outcomes for patients with CRC from the TCGA (n = 393). Four DMRs (MUC12, TBX20, CHN2, and B3GNT7) were selected as candidate prognostic markers for CRC. The prediction potential of selected DMRs was validated by the targeted bisulfite sequencing method in an independent cohort with 251 Chinese CRC patients. DMR methylation scores (DMSs) were constructed to evaluate the prognosis of CRC. Results of the validation cohort confirmed that higher DMSs were associated with poor overall survival (OS) of CRC, with hazard ratio (HR) value ranged from 1.445 to 2.698 in multivariable Cox models. Patients in the high prognostic index (high-PI) group showed a markedly unfavorable prognosis compared to the low-PI group in both TCGA discovery cohort (HR = 3.508, 95%CI: 2.196–5.604, P < 0.001) and independent validation cohort (HR = 1.912, 95%CI: 1.258–2.907, P = 0.002).     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Long-term outcomes of induction chemotherapy followed by intensity-modulated radiotherapy and adjuvant chemotherapy in nasopharyngeal carcinoma patients with N3 disease

ObjectivesTo evaluate long-term outcomes of induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) and adjuvant chemotherapy (AC) in nasopharyngeal carcinoma (NPC) patients with N3 disease.Materials and methodsFrom September 2005 to August 2016, 143 patients confirmed NPC with the 8th AJCC/UICC staging criteria N3 were reviewed. All patients received IC followed by IMRT and AC.ResultsAfter a median follow-up of 67 months, the 5-year and 10-year overall survival (OS), progression-free survival (PFS), distant metastasis free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) were 75.7% and 61.6%, 61.2% and 53.4%, 73.1% and 72.1%, 92.4% and 87%, 88.9% and 81.8%, respectively. Multivariate analyses indicated that T stage (P = 0.001) appeared to be prognostic factors for OS. T stage (P = 0.001 and P = 0.002) and neck lymph node necrosis (P = 0.015 and P = 0.045) were independent predictors of PFS and DMFS. The acute toxicities were mainly grade 1/2 hematologic toxicities in patients treated with IC+IMRT+AC, and severe toxicities were uncommon.ConclusionsIC followed by IMRT and AC achieved satisfactory long-term survival outcomes in NPC patients with N3 disease. Neck lymph node necrosis and late T stage served as predictors of poor prognosis for patients.     

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

BackgroundAlthough immunotherapy greatly extends overall survival (OS) of patients with extensive-stage small cell lung cancer (ES-SCLC), a number of patients develop immunotherapy resistance (IR). Patterns of failure in ES-SCLC are not clarified. Our study aims to explore the clinical pattern of IR and prognostic factors for these patients.MethodsThe study was conducted from 117 ES-SCLC patients with immunotherapy between 2018 and 2022. Chi-square tests and Fishers' exact tests was used to explore failure patterns in different populations. Survival analyses of different progression patterns and subsequent treatment regimens were conducted by Kaplan–Meier curves and log-rank test.Results86 (73.5%) patients experienced IR. The patients with smoking (never smoker vs. current or ex-smoker, 59.5 % vs. 81.3%, P = 0.010), liver metastasis (extrahepatic metastasis vs. intrahepatic metastasis, 73.6 % vs. 90.9%, P = 0.050), and distant metastasis status (no distant metastasis vs. distant metastasis, 39.1 % vs. 81.9%, P<0.001) were associated with IR rates. Liver progression had a lower incidence in 1st line immunotherapy (1st line vs. ≥2nd lines, 14.0 % vs. 41.7%, P = 0.004) and a higher incidence in multiple progression (multiple progression vs. Oligo-progression, 39.4 % vs. 17.0%, P = 0.021). Cranial (41.7 % vs. 16.1%, P = 0.012) and distant lymph node (16.7 % vs. 3.2%, P = 0.049) progression were the main failure model for acquired IR in comparison to primary IR. Patients with new lesion progression only (17.73 vs. 9.17 months, P = 0.013) and non-hepatic progression (14.23 vs. 11.67 months, P = 0.042) had a longer OS. Patients in cross-line immunotherapy after IR had a favourable prognosis (17.07 vs. 11.93 months, P = 0.007).ConclusionThe most common failure pattern of immunotherapy for ES-SCLC was lung and regional lymph node progression. Brain and liver progression were the most common extra thoracic failure sites for 1st line and 2nd and more lines immunotherapy, respectively. There was a higher probability of primary IR in 2 lines and above immunotherapy. Patients with new only progression site and cross-line rechallenge immunotherapy had a better prognosis.     

High TMPRSS4 expression is a predictor of poor prognosis in cervical squamous cell carcinoma

Objective The aim of this study was to clarify the clinical role of TMPRSS4 expression in cervical squamous cell carcinoma (CSCC) and to investigate the role of TMPRSS4 in predicting outcomes of patients with CSCC. Methods The retrospective study enrolled 87 patients diagnosed with CSCC between 2004 and 2006. TMPRSS4 expression in CSCC was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. The impact of TMPRSS4 expression on 5-year disease-free survival (DFS) and 5-year overall survival (OS) was assessed by Kaplan–Meier analysis and Cox proportional hazards modeling. Results The high expression of TMPRSS4 was 63.2% in 87 patients with CSCC, and 17.5% in 40 patients with benign cervical disease (P < 0.001). High TMPRSS4 expression was significantly associated with tumor grade (P = 0.005), lymph node metastasis (P = 0.004), and deep cervical stromal invasion (P = 0.025). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P = 0.0205 and P = 0.0318, respectively). In multivariate Cox regression analysis, high expression of TMPRSS4 was a potential prognostic indicator for OS (P = 0.041) and DFS (P = 0.015). Conclusion Our findings suggest that TMPRSS4 might play an important role in the progression of CSCC. TMPRSS4 could be a potential prognostic marker of CSCC.     

The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

PurposeTo explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs).MethodsWe systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients’ OS between the non-ICIs group and meta-analysis results.ResultsOf 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31–3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64–2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21–0.28; P < 0.001) and PFS (HR = 0.38; 95% CI: 0.34–0.42; P < 0.001). Furthermore, compared with non-ICIs group from the TCGA database, immunotherapy can improve OS in some cancer types with high TMB and better prognosis, including colorectal cancer, gastric cancer, lung cancer, melanoma and pan-cancer.ConclusionTMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. If there is a standard for TMB assessment and cut-off, it could improve the management of different cancers.     

Preoperative albumin-to-globulin ratio predicts survival in patients with non-small-cell lung cancer after surgery

The prognostic value of the preoperative albumin-to-globulin ratio (AGR) has not been investigated in non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the clinical applicability of the preoperative AGR to predict the prognosis in patients with NSCLC. We retrospectively enrolled 545 patients with stage I/II/III NSCLC who underwent surgery at our institution. The cutoff value for preoperative AGR was calculated by using a receiver operating characteristic curve analysis. A low AGR was associated with several clinicopathological variables related to tumor progression. In the multivariate analyses, the preoperative AGR was identified as an independent prognostic factor for disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.005). For patients with stage II and III with a preoperative AGR ≤ 1.43, the surgery plus chemotherapy group had a significantly longer DFS and OS than the surgery alone group (P = 0.002 and P = 0.001, respectively); however, a significant difference in DFS and OS between these two groups was not observed in patients with stage II and III with an AGR > 1.43 (P = 0.808 and P = 0.842, respectively). The preoperative AGR is an independent, significant predictor of DFS and OS in patients with NSCLC. Our results also demonstrate that the preoperative AGR might be a predictive marker of the therapeutic effect of postoperative chemotherapy in patients with stage II and III NSCLC.     

Prognostic value of the post-operative red blood cell distribution width in patients with rectal cancer with neoadjuvant chemoradiation followed by surgery

Purposes: Several studies have reported that elevated red cell distribution width (RDW) is related to poor prognosis in several cancers; however, the prognostic significance of perioperative RDW in patients with rectal cancer that received neoadjuvant chemoradiation therapy (NACRT) is unclear.Methods: A total of 120 patients with rectal cancer who received NACRT followed surgery were retrospectively reviewed from Affiliated Cancer Hospital of Zhengzhou University between 2013 and 2015. Data for peripheral blood tests prior to the initiation of NACRT, before surgery and first chemotherapy after surgery were collected, respectively. The optimal cutoff values of RDW were determined by ROC analysis, respectively. The relationship between RDW and the prognosis of patients was evaluated by the Kaplan Meier method, respectively.Results: The post-operative RDW^High patients had significantly worse 5-year overall survival (OS, P=0.001) and disease-free survival (DFS, P<0.001) than the post-operative RDW^Low patients, respectively. Whereas high pre-operative RDW was the only marker correlated with worse DFS (P=0.005) than the pre-operative RDW^Low patients, no relationship was found between pre-RDW and prognosis (OS, P=0.069; DFS, P=0.133). Multivariate analysis showed post-operative RDW had better predictive value than pre-RDW and pre-operative RDW.Conclusion: Post-operative RDW might be a useful prognostic indicator in patients with rectal cancer received neoadjuvant chemoradiation.