SERPINB7, TMEM158, and SERPINE1 signature as predictors of non-small-cell lung cancer prognosis after intravenous vitamin C treatment

Background: Vitamin C (VitC) has been proposed as a potential anti-cancer agent for prolonging progression-free survival (PFS) and overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. However, VitC has only been shown to be effective for some patients, and the mechanism in those who have benefitted from it remains unknown. We aimed to explore whether gene expression could predict IVC benefit for patients with NSCLC. Methods: H1299 and PC9 cells were treated with VitC and high-throughput sequencing was used for screening differential genes. Data from the Kaplan-Meier Plotter and the Human Protein Atlas databases were used for analysis of patient prognoses. In a retrospective study, 153 NSCLC patients from our Cancer Center were selected and divided into a control group (n = 81) and VitC group (n = 72) for immunohistochemical staining and prognosis analysis. Results: As a result, ZNF507, DLX4, and DDIT4 were found to be upregulated, and SERPINB7, TMEM158 and SERPINE1 downregulated in NSCLC cell lines following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that the downregulated genes, but not upregulated genes, presented an unfavorable prognostic predictor of OS in NSCLC patients. Further analysis showed that the combined three genes were more efficient at predicting survival than individually (AUC=0.77, 95%CI, 0.63-0.90). Moreover, high expression of SERPINB7, TMEM158, and SERPINE1 in resected tumour- tissues before VitC treatment was found to be associated with prolonged OS in patients with NSCLC who were treated with VitC. Conclusion: Overall, these data revealed that SERPINB7, TMEM158, and SERPINE1 formed a novel NSCLC prognosis gene set and could serve as a potential therapeutic target as well as predictive factor for VitC treatment in patients with NSCLC. Trial registration: Retrospectively registered (No: 2/2021-PRE-48) on July 13, 2021.