Prognostic Values, ceRNA Network, and Immune Regulation Function of SDPR in KRAS-mutant Lung Cancer

Abstract

Background: SDPR plays an important role in formation of pulmonary alveoli. However, the function and values of SDPR remain unknown in lung cancer. We explored prognostic values, expression pattern and biological function of SDPR in NSCLC and KRAS-mutant lung cancers.Methods: SDPR expression were evaluated by RT-qPCR, IHC, Western blotting based on human NSCLC cells, lung adenocarcinoma tissues array, KRAS-mutant transgenetic mice, TCGA and GEO datasets. The prognosis values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. The bioinformatics implication of SDPR including SDPR-combinated TFs and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules and tumor infiltration models were illustrated.Results: SDPR expression was downregulated among tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients in both lung cancer and KRAS-mutant subgroup. Meanwhile, ceRNA network to clarify the regulatory and biological functions of SDPR was constructed. Negative correlations were found between SDPR and immune checkpiont moluculars (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns.Conclusions: This study elucidates regulation network of SDPR in KRAS-mutant NSCLC, and illustrates correlations between low SDPR expression and suppressed immune systems, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.