Using Machine Learning Modeling to Explore New Immune-Related Prognostic Markers in Non-Small Cell Lung Cancer

Abstract

Objective To find new immune-related prognostic markers for non-small cell lung cancer (NSCLC). Methods We found GSE14814 is related to NSCLC in GEO database. The non-small cell lung cancer observation (NSCLC-OBS) group was evaluated for immunity and divided into high and low groups for differential gene screening according to the score of immune evaluation. A single factor COX regression analysis was performed to select the genes related to prognosis. A prognostic model was constructed by machine learning, and test whether the model has a test efficacy for prognosis. A chip-in-chip non-small cell lung cancer chemotherapy (NSCLC-ACT) sample was used as a validation dataset for the same validation and prognostic analysis of the model. The coexpression genes of hub genes were obtained by pearson analysis and gene enrichment, function enrichment and protein interaction analysis. The tumor samples of patients with different clinical stages were detected by immunohistochemistry and the expression difference of prognostic genes in tumor tissues of patients with different stages was compared. Results By screening, we found that LYN, C3, COPG2IT1, HLA.DQA1, and TNFRSF17 is closely related to prognosis. After machine learning, we constructed the immune prognosis model from these 5 genes, and the model AUC values were greater than 0.9 at three time periods of 1, 3, and 5 years; the total survival period of the low-risk group was significantly better than that of the high-risk group. The results of prognosis analysis in ACT samples were consistent with OBS groups. The coexpression genes are mainly involved B cell receptor signaling pathway and are mainly enriched in apoptotic cell clearance. Prognostic key genes are highly correlated with PDCD1, PDCD1LG2, LAG3, and CTLA4 immune checkpoints. The immunohistochemical results showed that the expression of COPG2IT1 and HLA.DQA1 in stage III increased significantly and the expression of LYN, C3, and TNFRSF17 in stage III decreased significantly compared with that of stage I. The experimental results are consistent with the previous analysis. Conclusion LYN, C3, COPG2IT1, LA.DQA1, and NFRSF17 may be new immune markers to judge the prognosis of patients with non-small cell lung cancer.

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“…The dewaxed tissue slice was soaked in 100% ethanol for 5min twice, 95% ethanol, 80% ethanol and distilled water for 5min respectively. The alkaline antigen repair solution (Tri-EDTA, pH=9) was heated to the boil in a pressure cooker, the tissue slice was placed in, and the time was timed for 2 min, then cooled to room temperature naturally (17). Incubate with 3% H 2 O 2 at room temperature for 10 min in dark, and then block with normal sheep serum solution at room temperature for 30min.…”

“…The primary antibody RP215 was added at 4℃ overnight and HRP-labeled secondary antibody was treated at room temperature for 30min. DAB color, hematoxylin redyeing (17).…”