收稿日期: 2025-06-05
网络出版日期: 2025-09-25
基金资助
国家自然科学基金地区科学基金项目(82360476);新疆维吾尔自治区自然科学基金重点项目(2022D01D39);新疆维吾尔自治区天山英才项目(2022TSYCCX0026);新疆维吾尔自治区区域协同创新专项——科技援疆计划(20241118681)
STAT activation inhibitory protein 2 is involved in reprogramming of lipid metabolism by regulating the prostate cancer development
Received date: 2025-06-05
Online published: 2025-09-25
目的 探讨STAT活化抑制蛋白2（protein inhibitor of the activated STAT2， PIAS2）基因在前列腺癌中的表达水平及其与临床病理特征的关系，以及PIAS2对前列腺癌脂质代谢重编程的潜在作用。 方法 采用癌症基因图谱（The Cancer Genome Atlas Program，TCGA）数据库和人类蛋白图谱（Human Protein Atas，HPA）免疫组化分析显示PIAS2蛋白的表达情况；采用qRT-PCR、Western bolt及免疫组化检测前列腺癌组织和周围癌旁组织中PIAS2的表达，并分析其与患者临床病理特征的关系；慢病毒感染前列腺癌细胞株PC-3M，稳定敲低PIAS2，通过超高效液相色谱质谱技术（UPLC-MS）进行脂质组学分析。 结果 TCGA分析显示PIAS2在前列腺癌组织的表达高于癌旁组织，HPA免疫组化分析显示PIAS2蛋白在前列腺癌组织高表达；PIAS2 mRNA和蛋白在前列腺癌中的表达量相较于癌旁组织均有显著提升，差异有统计学意义（P < 0.05）；免疫组织化学显示PIAS2蛋白表达主要定位在前列腺的细胞核，且前列腺癌组织的AOD值显著高于癌旁组织：临床病理参数研究结果显示，PIAS2与Gleason评分、TNM分期具有相关性（P < 0.05），而与患者年龄、PSA及淋巴结转移之间相关性无统计学意义（P > 0.05）；UPLC-MS分析提示，敲降PIAS2影响10种脂类变化，与shNC组相比，shPIAS2组的磷脂酰胆碱和磷脂酰乙醇胺的含量下调，磷脂酰肌醇、磷脂酰丝氨酸、二酰基甘油和三酰基甘油的含量上调。 结论 PIAS2蛋白的表达量在前列腺癌组织中明显升高，提示PIAS2与前列腺癌的发生发展有关，其发病机制可能与前列腺癌的脂质代谢异常相关。
关键词： 前列腺癌; STAT活化抑制蛋白2; 免疫组织化学; 脂质代谢重编程
李唯尊 , 邢晨 , 安恒庆 . STAT活化抑制蛋白2基因在前列腺癌中的表达水平及与临床病理特征的关系[J]. 实用医学杂志, 2025 , 41(18) : 2844 -2852 . DOI: 10.3969/j.issn.1006-5725.2025.18.009
Objective To investigate the expression level of the protein inhibitor of the activated STAT2 （PIAS2） gene in prostate cancer and its relationship with clinicopathological features， and the potential role of PIAS2 in reprogramming lipid metabolism in prostate cancer. Methods The Cancer Genome Atlas Program （TCGA） database and HPA immunohistochemical analysis were used to show the expression of PIAS2 protein； qRT-PCR， Western bolt and immunohistochemistry were used to detect PIAS2 in prostate cancer tissues and their paracancerous tissues. PIAS2 expression in prostate cancer tissues and its paracancerous tissues and analyzed its relationship with clinicopathological features of patients； lentivirus infected prostate cancer cell line PC-3M， which stably knocked down PIAS2， was analyzed by ultra performance liquid chromatography mass spectrometry （UPLC-MS） for lipidomics. Results TCGA analysis showed that the expression of PIAS2 in prostate cancer tissues was higher than that in paracancerous tissues， and HPA immunohistochemistry analysis showed that PIAS2 protein was highly expressed in prostate cancer tissues； the expression of PIAS2 mRNA and protein was significantly elevated in prostate cancer compared with that in paracancerous tissues， and the difference was statistically significant （P < 0.05）； immunohistochemistry showed that PIAS2 protein Expression of PIAS2 protein was mainly localized in the nucleus of prostate， and the AOD value of prostate cancer tissues was significantly higher than that of paraneoplastic tissues： the results of clinicopathological parameters showed that PIAS2 had correlation with Gleason score and TNM stage （P < 0.05）， while there was no statistically significant correlation with the age of the patients， PSA and lymph node metastasis； UPLC-MS analysis suggested that the knockdown of PIAS2 affected 10 lipid changes， with down-regulation of phosphatidylcholine and phosphatidylethanolamine and up-regulation of phosphatidylinositol， phosphatidylserine， diacylglycerol， and triacylglycerol in the shPIAS2 group compared with the shNC group. Conclusions The expression of PIAS2 protein was significantly elevated in prostate cancer tissues， suggesting that PIAS2 is associated with the development of prostate cancer， and its pathogenesis may be related to the abnormal lipid metabolism of prostate cancer.
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