UNASSIGNED: To investigate the impact that TTN mutation had on the gene heterogeneity expression and prognosis in patients with lung adenocarcinoma.
UNASSIGNED: In this study, the Cancer Genome Atlas (TCGA) dataset was used to analyze the TTN mutations in lung adenocarcinoma. Lung adenocarcinoma data was collected from the TCGA database, clinical information of patients was analyzed, and bioinformatics statistical methods were applied for mutation analysis and prognosis survival analysis. The results were verified using the GEO dataset.
UNASSIGNED: The incidence of TTN mutations in lung adenocarcinoma was found to be 73%, and it was related to the prognosis of lung adenocarcinoma. Ten genes were screened with significant contributions to prognosis. A prognosis model was constructed and verified by LASSO COX analysis in the TCGA and GEO datasets based on these ten beneficial factors. The independent prognostic factor H2BC9 for TTN mutation-driven gene heterogeneity expression was screened through multi-factor COX regression analysis.
UNASSIGNED: Our data showed that the gene heterogeneity expression, which was driven by TTN mutations, prolonged the survival of lung adenocarcinoma patients and provided valuable clues for the prognosis of TTN gene mutations in lung adenocarcinoma.

OBJECTIVE: E3 ubiquitin ligase ZNRF3 is linked to the pathogenesis of diseases and tumorigenesis. The present study aims to explore the expression of ZNRF3 and its association with prognostic survival of human colorectal carcinoma.
METHODS: A follow-up survey of 168 patients with colorectal carcinoma was performed, and specimens of colorectal tissues were collected for immunohistochemistry and Western blotting analyses. Furthermore, overexpression of ZNRF3 using transient transfection with the recombinant pEGFP-ZNRF3 plasmid and detection of apoptosis and proliferation were performed in HCT-116 cells.
RESULTS: The results showed a diverse feature of ZNRF3 staining, such as strong, moderate, weak, or negative, in colorectal carcinoma tissues. Interestingly, univariate Kaplan-Meier analysis showed that cases with strong or moderate expression of ZNRF3 showed an optimistic disease-free survival and overall survival compared with negative expression of ZNRF3, and multivariate Cox model demonstrated ZNRF3 as an independent prediction index for overall survival and disease-free survival. In vitro, the overexpression of ZNRF3 was related to the negative regulation of Wnt/β-catenin pathway and referred to an induction of apoptosis and suppression of proliferation in ZNRF3-transfected HCT-116 cells.
CONCLUSIONS: Our results suggest that the higher expression of ZNRF3 acts as a novel marker of indicating the optimistic prognosis of colorectal carcinoma by suppressing cancer cell growth and facilitating apoptosis.