| Objective: To investigate the expression of KRT23 gene in normal prostate and prostate cancer and its effect on the progression of prostate cancer,and to analyze the potential mechanism of KRT23 gene in prostate cancer.Methods: Firstly,the correlation between the expression of KRT23 and different clinical features of prostate cancer(age,PSA level(ng/ml),Gleason score,distant metastasis,survival rate,clinical stage and pathological stage)was analyzed in Taylor database.Then33 TCGA pan-cancer data matrices were downloaded from UCSC database,and the differences of KRT23 expression in 33 normal precancerous tissues and corresponding tumor tissues were analyzed by using "ggpubr" R language package.The transcriptional expression level of KRT23 in normal prostate tissue and prostate cancer tissue was analyzed based on TCGA database and GTEx database.The pathological tissues of 20 patients with prostate cancer were collected,We also analyzed the protein expression of KRT23 in prostate cancer and paraneoplastic tissues by immunohistochemistry.Then q-PCR and WB experiments were used to verify the difference of protein and mRNA expression of KRT23 in normal prostate cells(RWPE1)and prostate cancer cells(LNCa P,PC3,DU145).Finally,the "ggstatsplot" R language package was used to analyze the relationship between KRT23 gene expression and tumor mutation load(TMB)and microsatellite instability(MSI).GSEA3.0 software(BREAD Institute)was used to explore the potential mechanism of KRT23 in the occurrence and development of prostate cancer.Results: By analyzing the correlation between the expression of KRT23 and clinical features in Taylor database,it was found that the expression of KRT23 in prostate cancer patients with metastasis was significantly lower than that in patients without(P <0.014).The expression of KRT23 in high PSA level and high Gleason score group was significantly lower than that in low PSA level group(P <0.001)and low Gleason score group(P<0.0001).The results of pan-cancer analysis showed that the expression of KRT23 was different in breast invasive carcinoma(BRCA),cholangiocarcinoma(CHOL),colon adenocarcinoma(COAD)and so on.The expression of KRT23 gene in prostate cancer(PRAD)tissue was significantly lower than that in normal prostate tissue(P <0.001).Wilcoxon Signed-Rank test analysis in TCGA database showed that Expression of KRT23 was significantly lower in prostate cancer tissues than in normal prostate.(P <0.0001).Further included in the GTEX database of normal prostate tissues for difference analysis,the results showed that the expression of KRT23 in normal tissues was still significantly higher than that in tumor tissues(P <0.0001).The immunohistochemical results of human protein map(THPA)database showed that KRT23 protein was moderately expressed in normal prostate tissues and low in prostate cancer tissues.Similarly,KRT23 staining was higher in human prostate tissue than in prostate cancer tissue.At the cellular level,PCR and WB experiments showed that the expression of KRT23 protein and mRNA in normal prostate cells was higher than that in prostate cancer cells.There was a negative correlation between KRT23 gene expression and tumor mutation load(TMB)(Spearman(P =0.005),microsatellite instability(P =0.29)and microsatellite instability(P =0.13).GSEA enrichment analysis showed that KRT23 was significantly enriched with 9 tumor-related pathways,including KEGG＿MAPK＿SIGNALING＿PATHWAY,EGG＿PATHWAYS＿IN＿CANCER,EGG＿BASAL＿CELL＿CARCINOMA,KEGG＿VEGF＿SIGNALING＿PATHWAY,EGG＿WNT＿SIGNALING＿PATHWAY),KEGG＿APOPTOSIS,KEGG＿TGF＿BETA＿SIGNALING＿PATHWAY,KEGG＿PROSTATE＿CANCER and KEGG＿P53＿SIGNALING＿PATHWAY.Conclusion: The down-regulation of KRT23 expression in prostate cancer is associated with clinical factors such as High Gleason score,high PSA level and distant metastasis,kRT23 may be a promising biomarker for the diagnosis and treatment of prostate cancer progression.However,the specific molecular mechanism of KRT23 gene involved in the progression of prostate cancer needs further experimental verification. |
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