Search

Background: Colon cancer is a malignant tumor with high malignancy and a low survival rate whose heterogeneity limits systemic immunotherapy. Transforming growth factor-β (TGF-β) signaling pathway-related genes are associated with multiple tumors, but their role in prognosis prediction and tumor microenvironment (TME) regulation in colon cancer is poorly understood. Using bioinformatics, this study aimed to construct a risk prediction signature for colon cancer, which may provide a means for developing new effective treatment strategies., Methods: Using consensus clustering, patients in The Cancer Genome Atlas (TCGA) with colon adenocarcinoma were classified into several subtypes based on the expression of TGF-β signaling pathway-related genes, and differences in survival, molecular, and immunological TME characteristics and drug sensitivity were examined in each subtype. Ten genes that make up a TGF-β-related predictive signature were found by least absolute shrinkage and selector operation (LASSO) regression using colon cancer data from the TCGA database and confirmed using a Gene Expression Omnibus (GEO) dataset. A nomogram incorporating risk scores and clinicopathologic factors was developed to stratify the prognosis of patients with colon cancer for accurate clinical diagnosis and therapy., Results: Two TGF-β subtypes were identified, with the TGF-β-high subtype being associated with a poorer prognosis and superior sensitivity to immunotherapy. Mutation analyses showed a high incidence of gene mutations in the TGF-β-high subtype. After completing signature construction, patients with colon cancer were categorized into high- and low-risk subgroups based on the median risk score of the TGF-β-related predictive signature. The risk score exhibited superior predictive performance relative to age, gender, and stage, as evidenced by its AUC of 0.686. Patients in the high-risk subgroup had higher levels of immunosuppressive cell infiltration and immune checkpoints in the TME, suggesting that these patients had better responses to immunotherapy., Conclusions: Patients with colon cancer were divided into two subtypes with different survival and immune characteristics using consensus clustering analysis based on TGF-β signaling pathway-related genes. The constructed risk prediction signature may show promise as a biomarker for evaluating the prognosis of colon cancer, with potential utility for screening individuals for immunotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Speckle-type POZ protein (SPOP) plays an important role in maintaining genome stability. Disability or mutation of the SPOP gene has been reported to contribute to prostate cancer incidence and prognosis. However, the functions of SPOP in lung cancer remain poorly understood, especially in lung adenocarcinoma (LUAD). Here, we found that SPOP affects the LUAD cell response to radiation by regulating the DNA damage response (DDR) pathway. SPOP is widely expressed in lung cancer cell lines, and SPOP protein levels are upregulated when cells experience DNA damage. SPOP knockdown affects DDR repair kinetics, apoptosis and cell cycle checkpoints that are induced by IR (ionizing radiation). Furthermore, we found that SPOP positively regulates the expression of DDR factors Rad51 and Ku80. Taken together, these data indicate the essential roles of SPOP in the DDR signaling pathways and LUAD cell response to radiation., Competing Interests: None.

Objective: To investigate the expression level of protein tyrosine phosphatase non-receptor type 14 (PTPN14), and analyze the relationship between PTPN14 and clinical pathological features and prognosis of patients with cholangiocarcinoma., Methods: Expression of PTPN14 protein was detected by immunohistochemistry (IHC) in 57 cholangiocarcinoma tissues and corresponding adjacent normal tissues. The relationship between PTPN14 protein level and the clinical-pathological features of cholangiocarcinoma was analyzed using IBM SPSS 20.0 statistical software. The relationship between PTPN14 protein expression and 5-year overall survival of cholangiocarcinoma patients was investigated by survival curves., Results: IHC revealed that positive rates of PTPN14 protein were 49.1% and 75.4% in cholangiocarcinoma tissues and adjacent tissues, respectively. The expression of PTPN14 protein was significantly associated with TNM I, II, and differentiation degree of cholangiocarcinoma patients, but not significantly associated with age and gender of cholangiocarcinoma patients. The 5-year overall survival rate was higher in the PTPN14-positive patients than the PTPN14-negative ones., Conclusion: PTPN14 was down-regulated in cholangiocarcinoma, and negatively correlated with better clinical-pathological features and 5-year overall survival rate of cholangiocarcinoma.