HOXA基因在前列腺癌临床诊断中的价值及其对癌细胞增殖、迁移和侵袭的调控作用OA

Objective To explore the value of homeobox A cluster(HOXA)genes in the clinical diag-nosis of prostate cancer(PCa)and their effects on proliferation,migration and invasion.Methods The data in 499 cases of PCa and 52 healthy samples were obtained from the TCGA database.The"limma"package in R language was used to analyze the differentially expressed HOXA family genes based on the criterion that P<0.05 after correction of log2 fold change(FC)>2.The Kaplan-Meier method was used to calculate the rela-tionship between differential HOXA family members and the prognosis of PCa patients.The tumor-infiltra-ting immune cells(TIICs)level was calculated by using the CIBERSORT deconvolution algorithm.The PCa tissues and paracancerous normal tissues were collected to detect the expression levels of mRNA and protein expression levels of HOXA2,HOXA9 and HOXA10 by qPCR and Western blot and conducted the compara-tive analysis.The LNCaP cells were taken and transfected into si-NC,si-HOXA2,si-HOXA9 and si-HOXA10 respectively(si-NC group,si-HOXA2 group,si-HOXA9 group and si-HOXA10 group).The effects of silen-cing HOXA2,HOXA9 and HOXA10 genes on the PCa cell proliferation,migration and invasion were assessed through CCK-8,cell wound scratch assay and Transwell assay.Results The expression levels of HOXA1,HOXA2,HOXA7 and HOXA13 genes in PCa tissue were significantly lower than those in the normal prostate tissue(P<0.05),while the expression levels of HOXA9 and HOXA10 genes were significantly higher than those in the normal prostate tissue(P<0.05).The high expression of HOXA10 was associated with the poor prognosis in PCa patients(P<0.05),while low expressions of HOXA2 and HOXA9 were associated with the poor prognosis in PCa patients(P<0.05).HOXA2,HOXA9 and HOXA10 were correlated with the TIICs level in PCa tissue(P<0.05).The clinical trial results showed that the expression levels of HOXA2 and HOXA9 mRNA and protein in PCa tissue were significantly higher than those in the paracancerous normal tissues(P<0.05),while the expression levels of HOXA10 mRNA and protein were significantly lower than those in the paracancerous normal tissue(P<0.05).Silencing HOXA2 and HOXA9 genes significantly inhib-ited the proliferation,migration and invasion abilities of PCa cells,and reduced the expression levels of IL-10 and PD-L1,while silencing HOXA10 gene significantly increased the proliferation,migration and invasion abil-ities of PCa cells and increased the expressions of IL-10 and PD-L1(P<0.05).Conclusion HOXA family members have clinical diagnostic value in PCa,and HOXA2,HOXA9 and HOXA10 have the regulatory effects on the biological behaviors and immunosuppression of PCa cells.