COL11A1 Promotes Lung Adenocarcinoma Progression via PI3K/AKT/mTOR Pathway: Mechanistic Insights and Development of a COL11A1-Related Prognostic Signature

Weijie Wu¹Yuhang Chen²Chenlu Gong²Yujie Xiao²Caixia Zhang²Chonghua Hao³Xiaoyan Li³Guo-Yin Li^2*Xi Zhang^1*

• ¹Third Xiangya Hospital, Central South University, Changsha, China
• ²Zhoukou Normal University, Zhoukou, China
• ³Shanxi Provincial People’s Hospital, Tai yuan, China

Background Lung cancer is the top cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) accounting for 40% of cases and a 5-year survival rate below 20%. Delayed diagnosis, high recurrence, and drug resistance drive its poor prognosis. Collagen type XI alpha 1 chain (COL11A1) promotes tumor invasion and metastasis in multiple malignancies, but its regulatory mechanism and biological function in LUAD remain unclear. This study explored COL11A1’s role and mechanism in LUAD progression and constructed a prognostic model to support LUAD diagnosis and treatment. Methods COL11A1 expression patterns were analyzed via multi-omics of public datasets (TCGA_LUAD, GSE series) and clinical specimens. Western blot, chromatin immunoprecipitation (ChIP), and luciferase reporter assays clarified its regulatory mechanism. A COL11A1-related risk score (CRRS) and nomogram were established using LASSO-Cox regression and validated in multiple cohorts. Results COL11A1 was significantly upregulated in LUAD tissues, with high expression correlating closely with poor patient prognosis (AUC > 0.93). In vitro and in vivo experiments confirmed that COL11A1 promotes LUAD cell proliferation by activating the PI3K/AKT/mTOR pathway. The transcription factor TWIST positively regulates COL11A1 expression via direct binding to its promoter. CRRS, built on 7 core genes, effectively stratified patients into high- and low-risk groups with distinct survival outcomes in both training and validation cohorts, and correlated with drug sensitivity. The nomogram integrating CRRS and clinical variables efficiently predicted 1-, 3-, and 5-year survival rates (AUC > 0.71). Conclusions COL11A1 acts as an oncogene in LUAD, with its expression transcriptionally activated by TWIST and pro-tumor effects mediated via PI3K/AKT/mTOR pathway activation. CRRS and the nomogram offer potential references for LUAD prognostic evaluation and precision treatment.evaluation and precision treatment