Factors affecting the completion of concurrent chemotherapy and impact of non-completion on survival in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: To investigate whether completion of concurrent chemotherapy (CCT) improves overall survival (OS) of patients with locally advanced esophageal squamous cell carcinoma (ESCC), and to identify predictors of non-completion of CCT. METHODS: Data of ESCC patients treated with definitive concurrent chemoradiotherapy from January 2012 to December 2017 were retrospectively analyzed. CCT completion was defined as receiving recommended cycles with at most 25% dose reduction. Propensity score matching (PSM) analysis was applied to adjust unbalanced covariates between groups. Multivariate logistic regression model was used to identify factors affecting CCT completion. RESULTS: Of the 487 patients in the study, 194 patients (39.8%) had completed CCT. The majority (90.7%) had stage III-IV disease. Three-year OS rate was significantly higher in the completion group than non-completion group (35.4% vs. 30.3%; p = 0.025). Multivariate Cox analysis showed CCT completion was independently associated with longer OS (p = 0.005). The independent risk factors for CCT non-completion were weekly CCT regimen [odds ratio (OR) = 4.35, 95% CI 2.26-8.37; p < 0.001], clinical target volume (CTV)-elective nodal irradiation (ENI) (OR = 3.86, 95% CI 2.41-6.18; p < 0.001), planning target volume (PTV)/50 cm3 (OR = 1.09, 95% CI 1.02-1.16; p = 0.017), age (OR = 1.04, 95% CI 1.01-1.07, p = 0.011), and tumor in middle/lower esophagus (OR = 1.59, 95% CI 1.05-2.43, p = 0.030). CONCLUSION: CCT completion can provide superior OS for ESCC patients treated with definitive CCRT. Weekly CCT regimen, CTV-ENI, PTV, older age, and tumor location are independent predictors of non-completion of CCT.

Tripartite motif-containing 54 promotes gastric cancer progression by upregulating K63-linked ubiquitination of filamin C.

BACKGROUND: Tripartite motif (TRIM) proteins have been proved to contribute to cancer progression, while whether tripartite motif-containing 54 (TRIM54) could functionally influence gastric cancer (GC) progression remains elusive. METHODS: The expression level of TRIM54 and filamin C (FLNC) in GC was determined by Western blot and online database. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and Ethylenediurea (EdU) staining were performed to explore the effects of TRIM54 on GC cell proliferation. Transwell assay and wound healing assay were applied to detect the influence of TRIM54 on GC cell migration and invasion. Bioinformatics analysis and Co-immunoprecipitation assay (Co-Ip), Ubiquitination assay and Half-life assay were involved to explore the regulatory mechanism of TRIM54 on FLNC. RESULTS: TRIM54 was upregulated in GC tissues and cells, and a higher expression level of TRIM54 indicated a shorter overall survival of GC patients. The overexpression of TRIM54 significantly enhanced proliferation, migration, and invasion of GC cells, and inhibition of TRIM54 expression exerted reverse effects on GC cells. Mechanistically, TRIM54 was determined as a post-translational mediator of FLNC, and TRIM54 was co-immunoprecipitated with FLNC and degraded its protein level via K63-linked ubiquitination of FLNC. Notably, FLNC efficiently inhibited GC progression by TRIM54 overexpression. CONCLUSION: Collectively, our findings suggested that the TRIM54/FLNC axis could be considered as a potential prognostic biomarker for GC.

Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas.

BACKGROUND: We aimed to explore the relation of XPD and XPF variants with non-small cell lung cancer (NSCLC) risk and the effect of these variants on the sensitivity to cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas. METHODS: Eight single-nucleotide polymorphisms (SNPs) in XPD and XPF were genotyped by Agena MassARRAY platform among 506 NSCLC cases and 510 healthy controls. Correlation of XPD and XPF gene polymorphisms with NSCLC susceptibility and the response of cis-platin-based chemotherapy were analyzed with logistic regression by calculating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: XPD rs13181 (OR = 1.53, 95% CI: 1.04-2.24, p = 0.029) and rs1052555 (OR = 1.63, 95% CI: 1.05-2.53, p = 0.029) possibly contributed to the increased risk of lung adenocarcinoma, while XPD rs238406 (OR = 0.63, 95% CI: 0.43-0.94, p = 0.024) was a protective factor for lung squamous cell carcinoma. Age, gender, BMI, smoking, and drinking might affect the correlation of XPD and XPF polymorphisms with NSCLC risk. More importantly, XPD rs13181 (OR = 2.91, p = 0.015), XPD rs1052555 (OR = 2.67, p = 0.022), and XPF rs231127 (OR = 4.15, p = 0.008) were associated with treatment response in NSCLC patients underwent cisplatin-based chemotherapy. CONCLUSION: This study found that XPD and XPF variants might contribute to NSCLC risk and the response of cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas.

Role of ERCC5 polymorphisms in non­small cell lung cancer risk and responsiveness/toxicity to cisplatin­based chemotherapy in the Chinese population.

Non­small cell lung cancer (NSCLC) is the leading cause of cancer­related deaths worldwide. Cisplatin­based chemotherapy currently represents the main treatment option for patients with NSCLC. The aim of the present study was to evaluate effect of single nucleotide polymorphisms (SNPs) within the excision repair cross­complementing group 5 (ERCC5) gene on susceptibility to NSCLC, as well as the responsiveness to and toxicity of cisplatin chemotherapy. A total of 506 patients with NSCLC and 510 healthy controls were recruited for the present study. All DNA samples were genotyped by the Agena MassARRAY platform. Logistic regression analysis was carried out to assess the relationship between ERCC5 polymorphisms with NSCLC susceptibility and responsiveness to chemotherapy. The rs4771436 TG­GG genotype was associated with increased NSCLC risk. When the data were stratified according to age, sex, tobacco smoking, body mass index and histological type, ERCC5 polymorphisms (rs2016073, rs4771436, rs11069498 and rs4150330) were associated with NSCLC risk. Furthermore, the A allele and GA­AA genotype of rs11069498 were related to the response to chemotherapy. ERCC5 (rs11069498 and rs4150330) polymorphisms were associated with the increased risk of toxicity. However, rs4771436 in ERCC5 gene was significantly correlated with the reduced risk of toxicity. These results suggested a potential relationship between ERCC5 polymorphisms, the risk of NSCLC and the sensitivity to cisplatin­based chemotherapy among Chinese populations.

RAD52 variants influence NSCLC risk in the Chinese population in a high altitude area.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 80% of diagnosed lung cancer patients. RAD52 has been reported to be associated with the development of squamous cell lung carcinoma. In this study, we assessed the relationships of RAD52 genetic polymorphisms and NSCLC risk among the Chinese population at high altitude. METHODS: Eight single nucleotide polymorphisms (SNPs) of RAD52 were genotyped in the Agena MassARRAY platform among 506 NSCLC patients and 510 healthy controls. We examined the association of RAD52 polymorphisms with NSCLC risk using odds ratios (ORs) and 95% confidence intervals (CIs) via multiple genetic models. RESULTS: The rs10774474 A allele was related to a decreased risk of NSCLC in a high altitude population of China (OR = 0.82, 95% CI = 0.69-0.98, p = 0.032), whereas mutant alleles of rs1051672, rs7310449, rs1051669, rs6413436, rs4766377 and rs10849605 significantly increased NSCLC risk. Haplotype analysis showed that four haplotypes of RAD52 polymorphisms conferred an enhanced susceptibility to NSCLC (Ars1051672Grs7310449Trs1051669Ars6413436: OR = 1.29, p = 0.021; Grs1051672Ars7310449Crs1051669Grs6413436: OR = 1.21, p = 0.027; Grs4766377Crs12822733Trs10774474Crs10849605: OR = 1.26, p = 0.032; Ars4766377Crs12822733Ars10774474Trs10849605: OR = 1.21, p = 0.032). CONCLUSIONS: Our findings suggested the remarkable association of RAD52 polymorphisms with NSCLC risk among the Chinese population in a high altitude area. The reviews of this paper are available via the supplemental material section.

CK20 mRNA Expression in Serum as a Biomarker for Colorectal Cancer Diagnosis: A Meta-analysis.

The aim of this study was to evaluate the diagnostic value of serumCK20 mRNA as a biomarker for colorectal cancer diagnosis by meta-analysis. Clinical studies related to serum CK20 mRNA expression for colorectal cancer diagnosis were searched in the databases of Pubmed, Cochrane Library, Embase, ISI Web of Knowledge, CNKI and Wanfang. The number of true positive (tp), false positive (fp), false negative (fn) and true negative (tn) of the original included publications were extracted by two reviewers independently. The diagnostic sensitivity, specificity, positive likely hood ratio (+LR), negative likelyhood ratio (-LR), diagnostic odds ratio (DOR) and area under the symmetric ROC curve (AUC) were pooled by random or fixed effect method according to the statistical heterogeneity among the studies. After screening the databases, nineteen publications met the inclusion criteria and were finally included in this meta-analysis. The diagnostic sensitivity and specificity were pooled by random effect model(I2>50%). The pooled diagnostic sensitivity and specificity of CK20 mRNA in serum as biomarker for colorectal cancer were 0.49 (95% CI:0.46 to 0.51) and 0.94 (95%CI:0.92-0.96) respectively. The pooled +LR and -LR were 10.90 (95%CI:5.78 to 20.55) and 0.51 (95%CI:0.45 to 0.57) respectively by random-effect method. The pooled DOR was 22.31 with the 95% CI of 11.65 to 42.71. The pooled area under the ROC curve (AUC) was 0.72for CK20 mRNA in serum as a biomarker for colorectal cancer diagnosis. Conclusion Serum CK20 mRNA expression was significantly elevated in colorectal cancer patients which could be a promising serum biomarker for colorectal cancer diagnosis with high specificity.

Lymphocyte/Monocyte Ratio is a Novel Predictor for Early Stage Extranodal Natural Killer/T-cell Lymphoma, Nasal Type.

Objective: Great heterogeneity exists in clinical behavior and survival outcome in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). In this study, we proposed lymphocyte/monocyte ratio (LMR) as a new prognostic factor for these early stage ENKTL. Methods: We retrospectively examined the LMR as a prognostic variable in a cohort of 379 patients with newly diagnosed stage IE/IIE ENKTL. The relationship between the LMR and clinicopathologic variables were analyzed in Kaplan-Meier log-rank survival analysis, and the Cox proportional hazards model was used to determine the survival significance of the LMR for both progression-free survival (PFS) and overall survival (OS). Results: Patients were categorized into two different groups based on the LMR using cut-off value of 2.0. The 5-year PFS rates in the low and high LMR group were 43.9% and 62.7%, respectively, and the 5-year OS rates in the two groups were 59.1% and 77.7%, respectively. In multivariate analysis, low LMR at diagnosis was associated with worse PFS (hazard ratio 1.611, 95% confidence interval: 1.027-2.525, P =0.038) independent of age (P=0.033) and treatment stratagem (P<0.001), and indicated worse OS (hazard ratio 2.003, 95% confidence interval: 1.124-3.569, P =0.018) independent of age (P=0.007), LDH level (P=0.042), local tumor invasiveness (P=0.008), and treatment stratagem (P<0.001). Conclusion: The LMR is an independent prognostic factor for both DFS and OS in patients with stage IE/IIE ENKTL, and provides additional prognostic value beyond standard clinicopathological parameters.