Unraveling the gender-specific molecular landscape of lung squamous cell carcinoma progression

Lung squamous cell carcinoma (LUSC) is a type of non-small cell lung cancer that is the most common and deadly type of lung cancer, originating from the cells lining the bronchi. The progression of LUSC is influenced by various factors, such as genetic, viral, environmental and hormonal factors, immune system response, and smoking history. Despite extensive studies aimed at improving patient survival, the role of gender-specific molecular variants in LUSC progression remains unclear. Using a systems biology approach, combining differential gene expression, network analysis, and machine learning, aberrant mRNA and ncRNAs implicated in LUSC have been identified to improve patient survival, stratify patients and develop novel prognostic strategies. Furthermore, a systematic analysis of the prognostic implications and functional annotations of the molecular variants results in the filtering of key protein-coding genes and non-coding RNAs that are involved in tumor progression. We found several common molecular variants in both genders, including 4 mRNA, 4 miRNAs, and 27 lncRNAs. Among the shared lncRNAs, 5 were novel for both genders. These were found to have a poor prognostic performance in patients with lung cancer. The key players are involved in DNA replication, nucleotide excision repair, complement and coagulation cascades, and estrogen signaling pathways. In this study, we report lncRNAs (PVT1, FAM13A-AS1, LINC00461, NAV2-AS5, PRICKLE2-AS1, and VCAN-AS1) that may function as oncogenes or tumor suppressors by regulating the expression of coding genes, such as RAB24, HECW2, LGR4, and FKBP5. These lncRNAs and coding genes may play important roles in LUSC development and progression.