Department of Oncology and Radiotherapy, University Hospital of Split, 21000 Split, Croatia.
Laboratory of Morphology, Department of Histology and Embryology, School of Medicine, University of Mostar, 88000 Mostar, Bosnia and Herzegovina.
Int J Mol Sci. 2024 Nov 12;25(22):12120. doi: 10.3390/ijms252212120.
Precision medicine is a developing trend in oncology, and it includes the prognosis and treatment of advanced-stage ccRCC. New predictive factors and therapeutic targets for this disease are steadily needed. The aim of this study was to explore the tumor expression of inversin as a potential prognostic factor and/or therapeutic target in ccRCC. We compared the expression of inversin between primary ccRCC and normal renal tissues by using immunohistochemistry and rtPCR in our cohort, and we also analyzed publicly available data from the TCGA-KIRC cohort. We found that the expression of inversin was significantly lower in primary tumor tissue, in comparison to solid normal tissue. Data from the KIRC study confirmed that a lower expression level in ccRCC was significantly related with the overall and disease-specific survival, as well as with a shorter progression-free interval ( < 0.05). Four out of ten inversin interactome partners were significantly related with the overall and disease-specific survival in ccRCC. A lower expression of was a negative survival predictor, while a higher expression of , , or was related with a lower survival. The expression of and its interactome partners in ccRCC was correlated with the differentiation of the tumor and metastasis. The expression of and its partners was also correlated with tumor leukocyte infiltration and the expression of immune checkpoint genes. The results of this study point to inversin and a distinguished group of its interactome partners as potential prognostic factors in ccRCC, with their predominant involvement in the modulation of the inflammatory infiltration of the tumor microenvironment and a strong relationship with the metastatic potential of the tumor.
精准医学是肿瘤学的一个发展趋势，它包括晚期 ccRCC 的预后和治疗。这种疾病需要不断有新的预测因素和治疗靶点。本研究旨在探讨反式高尔基网络 2（inversin）作为 ccRCC 的潜在预后因素和/或治疗靶点的肿瘤表达情况。我们通过免疫组化和 rtPCR 在我们的队列中比较了原发性 ccRCC 和正常肾组织中 inversin 的表达情况，还分析了 TCGA-KIRC 队列中的公开数据。我们发现，与实体正常组织相比，原发性肿瘤组织中 inversin 的表达明显降低。KIRC 研究的数据证实，ccRCC 中表达水平较低与总生存期和疾病特异性生存期以及无进展生存期较短显著相关（<0.05）。inversin 相互作用组的四个成员与 ccRCC 的总生存期和疾病特异性生存期显著相关。较低的表达是生存的负预测因子，而较高的 、 或 的表达与较低的生存相关。ccRCC 中 的表达及其相互作用组与肿瘤的分化和转移有关。 的表达及其伙伴的表达也与肿瘤白细胞浸润和免疫检查点基因的表达有关。本研究的结果表明，inversin 和其相互作用组中的一组可能是 ccRCC 的潜在预后因素，它们主要参与调节肿瘤微环境的炎症浸润，并与肿瘤的转移潜能有很强的关系。
