Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer. With the in-depth exploration of cell death manners, numerous studies found that anoikis is an important mechanism that associated with treatment. Therefore, we aimed to explore the prognostic value and treatment guidance of anoikis in NSCLC patients. In the current study, we first constructed a prognostic model based on the anoikis-related genes based on bulk RNA-sequencing and single-cell RNA-sequencing (scRNA-seq) dataset. Then, immuno-correlations of anoikis-related risk scores (ARGRS) were analyzed. In addition, HMGA1, a risky gene in ARGRS, was further explored to define its expression and immuno-correlation. Results showed that patients with higher ARGRS had worse clinical outcomes. Moreover, the five genes in the prognostic model were all highly expressed on tumor cells. Moreover, further analysis found that the ARGRS was negatively correlated with ImmuneScore, but positively with tumor purity. Besides, patients in the ARGRS-high group had lower levels of immunological characteristics, such as the immune-related signaling pathways and subpopulations. Additionally, in the immunotherapy cohorts, patients with the ARGRS-high phenotype were more resistant to immunotherapy and tended to not achieve remission after treatment. Last, HMGA1 was chosen as the representative biomarker, and analysis of the in-house cohort showed that HMGA1 was highly expressed in tumor tissues and correlated with decreased T cell infiltration. To sum up, ARGRS was correlated with a desert tumor microenvironment and identified immune-cold tumors, which can be a novel biomarker for the recognition of immunological characteristics and an immunotherapeutic response in NSCLC.
Keywords: HMGA1; NSCLC; anoikis; gene signature; immunotherapy.