Association of Increased MIEN1 Copy Number With Worse Outcomes in Lung Adenocarcinoma and Cervical Cancer

Lung adenocarcinoma is the most common subtype of lung cancer and a significant contributor to cancer mortality globally. This has driven the development of targeted therapies, particularly those aimed at genetic alterations in certain genes, such as EGFR and ALK. ERBB2 (HER2) has also emerged as a potential oncogenic driver and therapeutic target in lung adenocarcinoma. Notably, ERBB2 is in close proximity on chromosome 17 to GRB7 and MIEN1, which are potential contributors to invasion and metastasis. Using TCGA-LUAD (The Cancer Genome Atlas Lung Adenocarcinoma) and CPTAC-3 (Phase III of the Clinical Proteomic Tumor Analysis Consortium) lung adenocarcinoma datasets, copy number variations (CNVs) for GRB7, ERBB2, and MIEN1 and their associations with various survival parameters were obtained. Results indicated that increased copy number (CN) of MIEN1 was significantly associated with worse disease-free survival (DFS) in both TCGA-LUAD and CPTAC-3 lung adenocarcinoma datasets and was significantly associated with worse progression-free survival (PFS) in the TCGA-LUAD dataset. There is also evidence showing a similar relationship in cervical cancer, which also has established links to ERBB2. CNV analyses in the TCGA-CESC and CGCI-HTMCP-CC (Cancer Genome Characterization Initiative-HIV+ Tumor Molecular Characterization Project-Cervical Cancer) cervical cancer datasets revealed that only increased CN of MIEN1 was statistically significantly associated with worse overall survival (OS) in both datasets. These CNV analyses suggest that MIEN1 should be further investigated as a potential contributor to oncogenesis.