Pan-Cancer Analysis of Prognostic and Immune Infiltrates for the TMEM65, Especially for the Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Transmembrane protein 65 (TMEM65) is an inner mitochondrial membrane protein involved in crucial cellular processes like autophagy and immune response.
• Growing interest exists in understanding the role of TMEM genes, including TMEM65, in cancer development and progression.
• A comprehensive pan-cancer analysis is needed to elucidate TMEM65's multifaceted roles in various malignancies.

Purpose of the Study:

• To conduct a pan-cancer investigation of Transmembrane protein 65 (TMEM65) expression and its clinical significance across 33 cancer types.
• To evaluate the association of TMEM65 with patient prognosis, tumor microenvironment (TME) features, and immune infiltration.
• To explore the correlation of TMEM65 with tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity.

Main Methods:

• Performed a pan-cancer analysis of TMEM65 expression using various public databases.
• Assessed the correlation of TMEM65 with overall survival (OS), progression-free interval (PFI), and post-progression survival (k-pFI).
• Analyzed TMEM65's association with immune infiltration, TME scores, TMB, MSI, neoantigens (NEO), and drug sensitivity, including pathway enrichment analysis (GSEA, GSVA) and nomogram construction for breast cancer.

Main Results:

• TMEM65 exhibited abnormal expression in 24 out of 33 cancer types, correlating with prognosis in several.
• TMEM65 showed significant associations with TME characteristics, immune cell infiltration (e.g., CD8 T effectors), and immune checkpoints.
• Correlations were found between TMEM65 and tumor mutational burden, microsatellite instability, neoantigens, drug sensitivity, and key cancer-related pathways (e.g., TGF-beta, TNF-alpha, hypoxia, pyroptosis, DNA repair, autophagy, ferroptosis).

Conclusions:

• Transmembrane protein 65 (TMEM65) plays a significant role in the prognosis of various cancers.
• TMEM65 is closely associated with tumor immunity and the tumor microenvironment.
• TMEM65 serves as a potential biomarker for cancer prognosis and immunotherapy response.