Objective  To explore the pan-cancer expression, immune infiltration, survival associations and drug sensitivity of key gemcitabine resistance genes, and to seek new alternative clinical therapies.

Methods  The gemcitabine resistance dataset was obtained through the GEO database. Differently expressed genes were screened, and the core differentially expressed genes were obtained through integrated analysis. The expression, immune infiltration, survival associations and drug sensitivity of key genes in pan-cancer were analyzed based on the cProSite, TIMER 2.0 and GSCA platforms.

Results  The key differential genes for gemcitabine resistance were SERPINB2 and CALB1. The expression of SERPINB2 was significantly increased in colon adenocarcinoma, lung squamous cell carcinoma, and skin cutaneous melanoma (P<0.001), and significantly decreased in breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, liver hepatocellular carcinoma, and lung adenocarcinoma (P<0.001). The expression of CALB1 was significantly increased in head and neck squamous cell carcinoma, lung squamous cell carcinoma and uterine corpus endometrial carcinoma (P<0.001), and significantly decreased in breast invasive carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma and thyroid carcinoma (P<0.001). The expressions of SERPINB2 and CALB1 were negatively correlated with the infiltration levels of B cell, Gamma_delta T cell, CD4_T, etc., in various cancers; and were positively correlated with the infiltration levels of iTreg, nTreg, macrophage, etc. Compared to CALB1, the differential expression of SERPINB2 had a greater impact on the survival of cancer patients in pan-cancer. The correlation analysis results between gene expression and drug sensitivity showed that SERPINB2 was significantly positively correlated with belinostat (r=0.186, FDR<0.001). CALB1 had the highest positive correlation with BRD-K99006945 (r=0.137, FDR<0.05), and the highest negative correlation with PD 153035 (r=-0.246, FDR<0.001).

Conclusion  The abnormal expressions of key gemcitabine resistance genes SERPINB2 and CALB1 were closely related to the occurrence and development of various cancers. The expressions of SERPINB2 and CALB1 were associated with the poor prognosis of cancer patients. The expression levels of small molecules belinostat and BRD-K99006945 were significantly positively correlated with the key genes of gemcitabine resistance, and they might be candidate drugs with antagonistic potential, which required further research.

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