Construction and validation of a signature for T cell-positive regulators related to tumor microenvironment and heterogeneity of gastric cancer.

Background: Positive regulators of T cell function play a vital role in the proliferation and differentiation of T cells. However, their functions in gastric cancer have not been explored so far. Methods: The TCGA-STAD dataset was utilized to perform consensus clustering in order to identify subtypes related to T cell-positive regulators. The prognostic differentially expressed genes of these subtypes were identified using the least absolute shrinkage and selection operator (LASSO) regression analysis. To validate the robustness of the identified signature, verification analyses were conducted across the TCGA-train, TCGA-test, and GEO datasets. Additionally, a nomogram was constructed to enhance the clinical efficacy of this predictive tool. Transwell migration, colony formation, and T cell co-culture assays were used to confirm the function of the signature gene in gastric cancer and its influence on T cell activation. Results: Two distinct clusters of gastric cancer, related to T cell-positive regulation, were discovered through the analysis of gene expression. These clusters exhibited notable disparities in terms of survival rates (P = 0.028), immune cell infiltration (P< 0.05), and response to immunotherapy (P< 0.05). Furthermore, a 14-gene signature was developed to classify gastric cancer into low- and high-risk groups, revealing significant differences in survival rates, tumor microenvironment, tumor mutation burden, and drug sensitivity (P< 0.05). Lastly, a comprehensive nomogram model was constructed, incorporating risk factors and various clinical characteristics, to provide an optimal predictive tool. Additionally, an assessment was conducted on the purported molecular functionalities of low- and high-risk gastric cancers. Suppression of DNAAF3 has been observed to diminish the migratory and proliferative capabilities of gastric cancer, as well as attenuate the activation of T cells induced by gastric cancer within the tumor microenvironment. Conclusion: We identified an ideal prognostic signature based on the positive regulators of T cell function in this study.

Corrigendum: Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer.

[This corrects the article DOI: 10.3389/fgene.2022.1038207.].

A signature constructed with mitophagy-related genes to predict the prognosis and therapy response for breast cancer.

Over the past decades, the incidence and mortality rates of breast cancer (BC) have increased rapidly; however, molecular biomarkers that can reliably detect BC are yet to be discovered. Our study aimed to identify a novel signature that can predict the prognosis of patients with BC. Data from the TCGA-BRCA cohort were analyzed using univariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) analysis was performed to build a stable prognostic model. Subsequently, Kaplan-Meier (K-M) and receiver operating characteristic (ROC) analyses were performed to demonstrate the predictive power of our gene signature. Each patient was assigned to either a low- or high-risk group. Patients with high-risk BC had poorer survival than those with low-risk BC. Cox regression analysis suggested that our signature was an independent prognostic factor. Additionally, decision curve analysis and calibration accurately predicted the capacity of our nomogram. Thus, based on the differentially expressed genes (DEGs) of mitophagy-related tumor classification, we established a 13-gene signature and robust nomogram for predicting BC prognosis, which can be beneficial for the diagnosis and treatment of BC.

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer.

Breast cancer (BC) is one of the most common tumor types and has poor outcomes. In this study, a ubiquitination-related prognostic signature was constructed, and its association with immunotherapy response in BC was explored. A list of ubiquitination-related genes was obtained from the molecular signatures database, and a ubiquitination-related gene signature was obtained by least absolute shrinkage and selection operator Cox regression. The genes, TCN1, DIRAS3, and IZUMO4, had significant influence on BC outcomes. Patients were categorized into two clusters-a high-risk group with poor survival and a low-risk group with greater chances of controlling BC progression. Univariate and multivariate Cox regression analyses revealed that the risk signature was an independent prognostic factor for BC. Gene set enrichment analysis suggested that the high-risk group was enriched in cell cycle and DNA replication pathways. The risk score was positively linked to the tumor microenvironment and negatively correlated with the immunotherapy response. The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient's immunotherapy response.

Pan-cancer analysis of the angiotensin II receptor-associated protein as a prognostic and immunological gene predicting immunotherapy responses in pan-cancer.

Background: Understanding interior molecular mechanisms of tumorigenesis and cancer progression contributes to antitumor treatments. The angiotensin II receptor-associated protein (AGTRAP) has been confirmed to be related with metabolic products in metabolic diseases and can drive the progression of hepatocellular carcinoma and colon carcinoma. However, functions of AGTRAP in other kinds of cancers are unclear, and a pan-cancer analysis of AGTRAP has not been carried out. Methods and materials: We downloaded data from The Cancer Genome Atlas and Genotype-Tissue Expression dataset and The Human Protein Atlas databases and then used R software (version 4.1.1) and several bioinformatic tools to conduct the analysis. Results: In our study, we evaluated the expression of AGTRAP in cancers, such as high expression in breast cancer, lung adenocarcinoma, and glioma and low expression in kidney chromophobe. Furthermore, our study revealed that high expression of AGTRAP is significantly related with poor prognosis in glioma, liver cancer, kidney chromophobe, and so on. We also explored the putative functional mechanisms of AGTRAP across pan-cancer, such as endoplasmic reticulum pathway, endocytosis pathway, and JAK-STAT signaling pathway. In addition, the connection between AGTRAP and tumor microenvironment, tumor mutation burden, and immune-related genes was proven. Conclusion: Our study provided comprehensive evidence of the roles of AGTRAP in different kinds of cancers and supported the relationship of AGTRAP and tumorous immunity.

Tumor microenvironment-related multigene prognostic prediction model for breast cancer.

BACKGROUND: Breast cancer is an invasive disease with complex molecular mechanisms. Prognosis-related biomarkers are still urgently needed to predict outcomes of breast cancer patients. METHODS: Original data were download from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The analyses were performed using perl-5.32 and R-x64-4.1.1. RESULTS: In this study, 1086 differentially expressed genes (DEGs) were identified in the TCGA cohort; 523 shared DEGs were identified in the TCGA and GSE10886 cohorts. Eight subtypes were estimated using non-negative matrix factorization clustering with significant differences seen in overall survival (OS) and progression-free survival (PFS) (P < 0.01). Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to develop a related risk score related to the 17 DEGs; this score separated breast cancer into low- and high-risk groups with significant differences in survival (P < 0.01) and showed powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.729, 3-year AUC = 0.778, 5-year AUC = 0.781). A nomogram prediction model was constructed using non-negative matrix factorization clustering, the risk score, and clinical characteristics. Our model was confirmed to be related with tumor microenvironment. Furthermore, DEGs in high-risk breast cancer were enriched in histidine metabolism (normalized enrichment score [NES] = 1.49, P < 0.05), protein export (NES = 1.58, P < 0.05), and steroid hormone biosynthesis signaling pathways (NES = 1.56, P < 0.05). CONCLUSIONS: We established a comprehensive model that can predict prognosis and guide treatment.