Comprehensive Analysis of the Immune Implication of ACK1 Gene in Non-small Cell Lung Cancer

Activated Cdc42-associated kinase1 (ACK1), a non-receptor tyrosine kinase, has been considered as an oncogene and therapeutic target in various cancers. However, its contribution to cancer immunity remains uncertain. Here we first compared the profiles of immune cells in cancerous and normal tissues in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Next, we found that the immune cell infiltration levels were associated with the ACK1 gene copy numbers in lung cancer. Consistently, our RNA-seq data unveiled that the silencing of ACK1 upregulated several immune pathways in lung cancer cells, including the T cell receptor signaling pathway. The impacts of ACK1 on immune activity were validated by Gene Set Enrichment Analysis of RNA-seq data of 188 lung cancer cell lines from the public database. A pathway enrichment analysis of 35 ACK1-associated immunomodulators and 50 tightly correlated genes indicated the involvement of the PI3K-Akt and Ras signaling pathways. Based on ACK1-associated immunomodulators, we established multiple-gene risk prediction signatures using the Cox regression model. The resulting risk scores were an independent prognosis predictor in the TCGA lung cohorts. We also accessed the prognostic accuracy of the risk scores with a receiver operating characteristic methodology. Finally, a prognostic nomogram, accompanied by a calibration curve, was constructed to predict individuals' 3- and 5-year survival probabilities. Our findings provided evidence of ACK1's implication in tumor immunity, suggesting that ACK1 may be a potential immunotherapeutic target for non-small cell lung cancer (NSCLC). The nominated immune signature is a promising prognostic biomarker in NSCLC.