Identifying diagnostic markers and establishing prognostic model for lung cancer based on lung cancer-derived exosomal genes.

Abstract

Background: Lung cancer (LC) is the most common malignancy and the leading cause of cancer death. LC-derived exosomes have been found to play a critical role in tumor initiation, progression, metastasis and drug resistance. Therefore, the objective of this study is to identify prognostic markers based on lung cancer-derived exosomes in patients with different subtypes of lung cancer, including small cell lung cancer (SCLC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and large cell carcinoma (LCC). Additionally, we aim to develop corresponding prognostic models to predict the outcomes of these patients. Methods: In this study, the mRNAs information about LC-derived exosomes was collected from Vesiclependia database, and the mRNAs data of LCC, LUAD, LUSC and LCC tumors and paracancerous tissues was obtained from the GEO database and UCSC database. The prognostic models based on exosomes-related differential expression genes (ExoDEGs) by univariate Cox, LASSO, and multivariate Cox regression analyses. The independent prognostic value of the risk model was systematically analyzed. Results: A LUAD prognostic risk model of 12 ExoDEGs (CDH17, DAAM2, FKBP3, FLNC, GSTM2, PGAM4, HPCAL1, FERMT2, LYPD1, SNRNP70, KIR3DL2 and GPX3) and a LUSC prognostic risk model of 7 ExoDEGs (FGA, ERH, HID1, CSNK2A1, SLC7A5, ACOT7 and FUNDC1) were constructed. Kaplan-Meier curve, ROC curve and stratification survival analysis confirmed that the LUAD and LUSC risk models both possessed reliable predictive value for the prognosis of LUAD and LUSC patients. The expression level of ExoDEGs for building the LUAD and LUSC risk models is significantly correlated with immunosuppressive activity of patients, and the immunosuppressive activity is lower in the high-risk groups. Conclusions: We established a LUAD prognostic model with 12 ExoDEGs and a LUSC prognostic model with 7 ExoDEGs, which can be used as independent prognostic indicators for patients LUAD and LUSC. The identified ExoDEGs have the potential to be as prognostic markers and may also serve as novel candidate targets for the treatment of LUAD and LUSC.