Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046–2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays a crucial role in the stability of the programmed death-ligand 1 (PD-L1). However, there has been no previous study of CMTM6 in non-small cell lung cancer (NSCLC) and its association with PD-L1 has not been confirmed. The aim of this study was to investigate the expression of CMTM6 and PD-L1 and to confirm their predictive roles for anti-PD-1 therapy in non-small cell lung cancer. CMTM6 and PD-L1 immunohistochemical expressions were evaluated in 35 advanced, treatment-refractory NSCLC patients who received PD-1 inhibitor therapy. The correlation between CMTM6 and PD-L1 expression was also determined based on immunohistochemistry and RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) database. CMTM6 expression was positively correlated with PD-L1 expression in immunohistochemical data (Pearson’s r = 0.342 and p = .044). A positive correlation was also identified in the mRNA expression data. Using receiver operating characteristic curves, the levels of CMTM6 and PD-L1 expression which provided the best distinguishing point between responder versus non-responder to PD-1 inhibitors were 70 and 75 H-scores, respectively. The patients in the PD-1 inhibitor responder group had higher CMTM6 expressions in univariate logistic regression analysis (odds ratio (OR) = 5.333, p = .037). However, PD-L1 expression was not associated with response to PD-1 inhibitor (p = .288). In multivariate analysis, CMTM6 was also found to be an independent predictor of the response to PD-1 inhibitors (OR = 6.226, p = .032). CMTM6 expression can be a promising predictor useful for therapeutic decision-making regarding PD-1 inhibitors.

We examined the prognostic significance of Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3) expression and its correlations with mesenchymal phenotype and microvessel density in non-small cell lung carcinoma (NSCLC). A total of 268 NSCLC specimens were evaluated retrospectively by immunohistochemical staining for EDIL3, EMT markers (e-cadherin, β-catenin, and vimentin), and CD31 to measure microvessel density. EDIL3, e-cadherin, β-catenin, and vimentin were expressed in 16%, 22.8%, 3.7%, and 10.1% of the specimens, respectively. The mRNA level of EDIL3 in tumor was correlated with the level of EDIL3 protein expression using immunohistochemistry. In lung adenocarcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression, high vimentin expression, and increased microvessel density (P < 0.001, P = 0.001, and P = 0.023, respectively). In lung squamous cell carcinoma patients, EDIL3 expression was significantly correlated with low e-cadherin expression and high vimentin expression (P = 0.021 and P = 0.002, respectively). In lung adenocarcinoma patients, EDIL3 was an independent prognostic factor for overall survival in a multivariate analysis (hazard ratio: 2.552, P = 0.004). EDIL3 is significantly correlated with mesenchymal phenotype, angiogenesis, and tumor progression in lung adenocarcinoma.