Overexpression and diagnostic significance of INTS7 in lung adenocarcinoma and its effects on tumor microenvironment.

ABSTRACT

BACKGROUND: Lung cancer is the leading cause of death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. INTS7, one of the subunits of the integrator complex, is upregulated in several tumors. Thus, we aimed to investigate the expression profile and clinical significance of INTS7 in LUAD. METHODS: The expression profile of INTS7 was tested in TCGA database and clinical specimens. ROC curve was used to detect the diagnostic value of INTS7, CEA and INTS7 combined with CEA. Kaplan-Meier analysis was used to analyze the prognostic value of INTS7. Differentially expressed genes (DEGs) related to INTS7 were analyzed, and functional enrichment analysis was used to explore the potential mechanisms related to DEGs. The correlations between INTS7 and tumor-infiltrating immune cells, immune scores, stromal scores, and immune checkpoints were explored. Finally, the relationship between INTS7 expression and sensitivity to molecular-targeted therapy was examined. RESULTS: Data from TCGA database showed that INTS7 mRNA expression was substantially upregulated in LUAD, the AUC values of INTS7 for diagnosing LUAD were >0.8, combined detection of INTS7 and CEA could improve the diagnostic efficiency and early stage patients with high expression of INTS7 showed shorter overall survival. IHC analysis of clinical samples further verified the overexpression of INTS7 protein and confirmed the diagnostic value of INTS7 in LUAD, especially for patients at advanced stages with the AUC >0.8. A total of 192 DEGs were identified and DEGs were primarily involved in cell cycle, inflammatory response, and immune response. Moreover, INTS7 expression was negatively correlated with memory B cells, regulatory T cells (Treg), monocytes, resting myeloid dentritic cells and activated mast cells infiltration, and positively correlated with naive B cells, T follicular helper cells (Tfh), activated myeloid dentritic cells and neutrophils infiltration. In addition, patients with high expression of INTS7 showed less expression of immune checkpoints and exhibited less sensitivity to molecular-targeted drugs. CONCLUSION: INTS7 is a potential diagnostic biomarker for LUAD. And its expression level may correlate with tumor microenvireoment, immunotherapy responsiveness, and molecular-targeted therapy responsiveness in LUAD.