Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Physical Examination Center of Langfang Traditional Chinese Medicine Hospital, Langfang, Hebei, China.
Bull Exp Biol Med. 2024 Jan;176(3):363-368. doi: 10.1007/s10517-024-06025-y. Epub 2024 Feb 12.
In this retrospective study involving 112 patients with clear cell renal cell carcinoma (ccRCC), we analyzed clinical significance and prognostic value of the expression of BCCIP protein interacting with BRCA2 and CDKN1A and glutathione peroxidase 4 (GPX4). The expressions of mRNA and the corresponding proteins were evaluated using reverse transcription PCR and immunohistochemistry. In comparison with control samples of renal peritumoral tissue, the expressions of BCCIP and its mRNA in the tumor tissues were significantly down-regulated, while the expressions of GPX4 and the corresponding mRNA were significantly up-regulated. The down-regulation of BCCIP expression was closely related to histological grade, TNM stage, and lymph node metastasis (p<0.05). The GPX4 overexpression was closely related to tumor size, TNM stage, and the presence of distant metastasis. The Kaplan-Meier survival analysis showed that tumor size, TNM stage, lymph node metastasis, distant metastasis, expressions of BCCIP and GPX4 correlated with progression-free survival (p<0.05). Multivariate Cox regression showed that down-regulation of BCCIP expression and overexpression of GPX4, TNM stage, and distant metastasis were independent prognostic factors of progression-free survival. Thus, down-regulation of BCCIP expression and overexpression of GPX4 are indicatives of progression of ccRCC with poor prognosis. Hence, the control of expression of these proteins can be considered as a novel target for the treatment of ccRCC.
在这项涉及 112 例透明细胞肾细胞癌 (ccRCC) 患者的回顾性研究中,我们分析了 BCCIP 蛋白与 BRCA2 和 CDKN1A 以及谷胱甘肽过氧化物酶 4 (GPX4) 相互作用的表达的临床意义和预后价值。使用逆转录 PCR 和免疫组织化学评估 mRNA 和相应蛋白的表达。与肾肿瘤旁组织的对照样本相比,肿瘤组织中 BCCIP 及其 mRNA 的表达明显下调,而 GPX4 的表达及其相应的 mRNA 明显上调。BCCIP 表达下调与组织学分级、TNM 分期和淋巴结转移密切相关(p<0.05)。GPX4 过表达与肿瘤大小、TNM 分期和远处转移密切相关。Kaplan-Meier 生存分析表明,肿瘤大小、TNM 分期、淋巴结转移、远处转移、BCCIP 和 GPX4 的表达与无进展生存期相关(p<0.05)。多因素 Cox 回归显示,BCCIP 表达下调和 GPX4 过表达、TNM 分期和远处转移是无进展生存期的独立预后因素。因此,BCCIP 表达下调和 GPX4 过表达是 ccRCC 进展和预后不良的指标。因此,控制这些蛋白的表达可以被认为是治疗 ccRCC 的一种新靶点。