Integrated analysis of metabolome and transcriptome in esophageal squamous cancer cell KYSE30 and cisplatin-resistant KYSE30

The aim of this study is to investigate the gene biomarkers and metabolites for esophageal squamous cell carcinoma (ESCC) or cisplatin (DDP)-resistance ESCC through integrated analysis of transcriptome and metabolome. A total of 6,130 differentially expressed genes (DEGs) and 326 differentially expressed metabolites (DEMs) were identified in KYSE30 compared to HEEC, while compared to KYSE30, there were totally 1,179 DEGs and 224 DEMs in KYSE30/DDP. Profile #6 depicted the mRNA characteristics of KYSE30 obviously. Genes in profile #6 were mainly involved in platinum drug resistance, ferroptosis, and glutathione metabolism. Additionally, there were 124 common genes among the significantly upregulated genes in KYSE30 and KYSE30/DDP, which were mainly enriched in the immunoglobulin domains. PSG1, as a secreted protein in immunoglobulin superfamily, was distinctly positively correlated with CGA and 5-methylcytosine (m5C). Furthermore, a synchronous decrease in Fe2+ content and ROS production was found in KYSE30 and KYSE30/DDP. Not only that, the levels of GSH, GSSG, FTL, GPX4, and GCLC were increased, while ACSL4 was decreased in KYSE30 and KYSE30/DDP. These findings indicating the key role of ferroptosis/glutathione metabolism in the progress of ESCC. Meanwhile, PSG1, CGA and m5C are expected to be potential diagnosis biomarkers for ESCC patients resistant to DDP.