转录因子KLF7高表达与前列腺癌发生的相关性及其靶基因预测

Correlation between overexpression of KLF7 and carcinogenesis of prostate cancer and its target gene prediction

目的探讨KLF7高表达与前列腺癌(PCa)发生的相关性,并对其可能的下游靶基因进行筛选。方法比较前列腺增生(BPH)患者(n=22)以及PCa患者(n=30)血糖、血脂及一般资料的差异;调取石蜡包埋的前列腺组织标本,运用免疫组织化学法检测组织中KLF7及其下游因子IL-6,以及肿瘤发生相关因子E-钙粘蛋白、Ki67的表达量。运用统计学方法,比较各因子在BPH和PCa患者前列腺组织中的表达差异,并分析KLF7表达与各因子之间的相关性。运用Cistrome Data Browser数据库对KLF7可能的下游靶基因进行预测。结果 PCa患者血清中总前列腺特异性抗原(TPSA)含量显著高于正常体检及BPH个体(P<0.001);PCa患者前列腺组织中KLF7及IL-6表达量显著高于BPH患者前列腺组织(P<0.05),肿瘤发生相关因子Ki67表达量显著高于BPH患者前列腺组织(P<0.05),E-钙粘蛋白的表达量在两组间无显著差异。相关性分析结果显示:前列腺癌组织中KLF7的表达与患者血清中TPSA含量显著正相关(r=0.465,P=0.001),与癌组织中IL-6的表达显著正相关(r=0.437,P=0.014),与癌组织中Ki67的表达显著正相关(r=0.434,P=0.002),与癌组织中E-钙粘蛋白的表达显著正相关(r=0.473,P=0.009)。生物信息学分析结果显示:转录因子KLF7可能通过调控肿瘤相关基因STAT3,DDX20,ZNF233,ZNF581,ZNF487,ZNF580,ZNF391,ZNF793,HMGB1,DMAP1,CTNNB1,ZBTB45等参与肿瘤的发生发展。结论 KLF7高表达可能是前列腺癌发生的危险因素,前列腺癌组织中KLF7的表达与IL-6、Ki67以及E-钙粘蛋白的表达显著正相关。KLF7可能通过调控一系列肿瘤相关基因的表达参与肿瘤发生发展的过程。

Objective To investigate the correlation between KLF7 overexpression and the occurrence of prostate cancer( PCa),and to screen and verify its potential downstream target genes. Methods Compare the differences of blood glucose,blood lipid and general data between BPH( Benign prostatic hyperplasia) patients( n = 22) and patients with PCa( n = 30);The paraffin-embedded prostate tissue samples were collected,and the expression levels of KLF7 and its downstream factors IL-6,and tumor-associated factors E-cadherin and Ki67 were detected by immunohistochemistry. Using statistical methods to compare the expression differences of various factors in patients with BPH and PCa. Using bioinformatics methods to predict possible downstream target genes of KLF7. Results The serum TPSA content of PCa patients was significantly higher than that of normal physical examination and BPH individuals( P<0. 001);The expression of KLF7 and IL-6 in prostate cancer tissues of PCa patients was significantly higher than that of prostate tissues of BPH patients( P<0. 05),the expression level of Ki67 was significantly higher than that of prostate tissue in patients with BPH( P<0. 05),and the expression level of E-cadherin was not significantly different between the two groups. The results of correlation analysis showed that the expression of KLF7 in prostate cancer tissue was significantly positively correlated with the TPSA( r = 0. 465,P = 0. 001),IL-6( r =0. 437,P = 0. 014),Ki67( r = 0. 434,P = 0. 002),and E-cadherin( r = 0. 473,P = 0. 009). The results of bioinformatics analysis showed that the transcription factor KLF7 may be involved in the occurrence and development of tumors by regulating tumor-related genes STAT3,DDX20,ZNF233,ZNF581,ZNF487,ZNF580,ZNF391,ZNF793,HMGB1,DMAP1,CTNNB1,ZBTB45 and so on. Conclusion High expression of KLF7 may be a risk factor for prostate cancer. The expression of KLF7 in prostate cancer tissue is significantly positively correlated with the expression of IL-6,Ki67 and E-cadherin. KLF7 may participate in the process of tumorigenesis by regulating the expression of a series of tumor-related genes.