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We conducted a perspective study to investigate whether the expression of excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group G (XPG), breast cancer 1 (BRCA1), and ribonucleotide reductase M1 (RRM1) is correlated with clinical outcome of non-small cell lung cancer (NSCLC). Patients with histologically confirmed inoperable stages IIIB and IV NSCLC were collected and followed up until January 2012. Relative cDNA quantification for ERCC1, XPG, BRCA1, and RRM1 was performed using a fluorescence-based, real-time detection method. Cox regression analysis indicated that a high level of ERCC1 was associated with shorter overall survival (OS) and progression-free survival (PFS) times when compared with low expression, with adjusted hazard ratios (HRs) (95% confidence interval (CI)) of 2.25 (1.18-4.39) and 2.63 (1.33-5.25), respectively. High expression of BRCA1 was correlated with shorter OS and PFS times when compared with low expression, and the adjusted HRs (95% CI) were 3.29 (1.72-6.39) and 5.94 (2.80-13.06), respectively. Moreover, we found a significant correlation between BRCA1 expression and age (χ(2) = 4.14, P = 0.04) and stage (χ(2) = 5.26, P = 0.02). Our results suggest that ERCC1 and BRCA1 mRNA expressions are associated with PFS and OS in advanced NSCLC patients treated with platinum-based chemotherapy.

BackgroundPyroptosis is regulated by long non-coding RNAs (lncRNAs) in ovarian cancer (OC). Therefore, a comprehensive analysis of pyroptosis-related lncRNAs (PRLs) in OC is crucial for developing therapeutic strategies and survival prediction.MethodsBased on public database raw data, mutations in the landscape of pyroptosis-related genes (PRGs) in patients with OC were investigated thoroughly. PRLs were identified by calculating Pearson correlation coefficients. Cox and LASSO regression analyses were performed on PRLs to screen for lncRNAs participating in the risk signature. Furthermore, receiver operating characteristic (ROC) curves, Kaplan–Meier survival analyses, decision curve analysis (DCA) curves, and calibration curves were used to confirm the clinical benefits. To assess the ability of the risk signature to independently predict prognosis, it was included in a Cox regression analysis with clinicopathological parameters. Two nomograms were constructed to facilitate clinical application. In addition, potential biological functions of the risk signature were investigated using gene function annotation. Subsequently, immune-related landscapes and BRCA1/2 mutations were compared in different risk groups using diverse bioinformatics algorithms. Finally, we conducted a meta-analysis and in-vitro assays on alternative lncRNAs.ResultsA total of 374 patients with OC were randomized into training and validation cohorts (7:3). A total of 250 PRLs were selected from all the lncRNAs. Subsequently, a risk signature (DICER1-AS1, MIR600HG, AC083880.1, AC109322.1, AC007991.4, IL6R-AS1, AL365361.1, and AC022098.2) was constructed to distinguish the risk of patient survival. The ROC curve, K-M analysis, DCA curve, and calibration curve indicated excellent predictive performance for determining overall survival (OS) based on the risk signature in each cohort (p < 0.05). The Cox regression analysis indicated that the risk signature was an independent prognostic factor for OS (p < 0.05). Moreover, significant differences in the immune response and BRCA1 mutations were identified in different groups distinguished by the risk signature (p < 0.05). Interestingly, in-vitro assays showed that an alternative lncRNA (DICER1-AS1) could promote OC cell proliferation.ConclusionThe PRL risk signature could independently predict overall survival and guide treatment in patients with OC.

Objective: To explore the effect on radiosensitivity of arsenic trioxide (As 2 0 3 ) in conjunction with hyperthermia on the esophageal carcinoma EC-1 cell line. Method: Inhibition of EC-1 cell proliferation at different concentrations of As 2 0 3 was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC 50 value and choice of 20% of the IC 50 as the experimental drug concentration. Blank control, As 2 0 3 , hyperthermia, radiotherapy group, As 2 0 3 + hyperthermia, As 2 0 3 + radiotherapy, hyperthermia + radiotherapy and As 2 0 3 + hyperthermia + radiotherapy groups were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Flow cytometry (FCM) was used to detect changes in cell apoptosis and the cell cycle. Results: As 2 0 3 exerted inhibitory effects on proliferation of esophageal carcinoma EC-1 cells, with an IC 50 of 18.7 μmol/L. After joint therapy of As 2 0 3 + hyperthermia + radiotherapy, the results of FCM showed that cells could be arrested in the G 2 /M phase, and as the ratio of cells in G 0 /G 1 and S phases decreased, cell death became more pronounced. Conclusion: As 2 0 3 and hyperthermia exert radiosensitivity effects on esophageal carcinoma EC-1 cells, with synergy in combination. Mechanistically, As 2 0 3 and hyperthermia mainly influence the cell cycle distribution of EC-1 esophageal carcinoma cells, decreasing the repair of sublethal damage and inducing apoptosis, thereby enhancing the killing effects of radioactive rays.