Prognostic Value of CMTM6 Expression in Breast Cancer

Abstract Introduction CMTM6, a regulator of tumor cell PD-L1 stability via inhibiting lysosome-mediated degradation, is linked to anti-tumor immunity and tumorigenesis. However, its expression and prognostic value in breast cancer subtypes remain unclear. Methods We conducted an integrated bioinformatics analysis of CMTM6 using multiple public databases: cBioPortal for examining genetic alterations in TCGA breast cancer datasets; GEPIA for comparing expression between tumor and normal tissues; bc-GenExMiner 4.0 for assessing expression across subtypes and performing meta-analysis; Kaplan-Meier Plotter and the Human Protein Atlas for prognostic assessment. Results CMTM6 was ubiquitous in human tissues but low in normal breast (glandular/myoepithelial cells only). It was higher in breast cancer than normal tissues, lower in HER2-positive subtypes, higher in P53 wild-type tumors, and uncorrelated with lymph node status/age. Breast cancer CMTM6 gene alterations were rare (amplification: 0.56%; deep deletion: 0.14%). High CMTM6 (mRNA/protein) correlated with better overall survival, specifically in lymph node-positive and Luminal A subtypes, but not in other subtypes. Discussion CMTM6 is differentially expressed in breast cancer/subtypes and acts as a favorable prognostic indicator for lymph node-positive/Luminal A breast cancer, serving as a potential subtype-specific biomarker.