Constructing a folate metabolism gene signature for predicting prognosis in pulmonary neuroendocrine carcinomas

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experiments. The expression patterns of 26 folate metabolism related genes were evaluated between normal lung tissues and PNEC tumor tissues, and 20 of them exhibited differential expression. All of folate metabolism related genes were related to the prognosis of PNECS and 16 genes were identified as prognostic genes. Using SVM-RFE, RF, Xgboost and LASSO algorithm, three core genes were isolated from 16 prognostic genes. Based on the expression patterns of core genes, PNECs patients were divided into two clusters through consensus clustering algorithm. Cluster 1 was characterized by the worse survival, higher immune infiltration level, and sensitivity to chemotherapy. Compared with the HBEC cells, ALDH1L2 was notably overexpressed in NCI-H446 cells (SCLC cell line). ALDH1L2 knockdown significantly repressed the proliferation and migration capacity of tumor cells and increased the cell proportion in S phase. Our results indicated that folate metabolism gene signature is a reliable biomarker for PNECs. Classification based on this signature could be utilized to guide the treatment of PNECs patients and improve its prognosis.

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