肾透明细胞癌(ccRCC)的免疫生物化学特征:初步研究。
Immunobiochemical profile of clear cell renal cell carcinoma (ccRCC): A preliminary study.
发表日期:2023 Sep
作者:
Daniela Vargová, Ján Dargaj, Soňa Fraňová, Matúš Dohál, Ján Ľupták, Ján Švihra, Lukáš Briš, Marián Grendár, Martina Šutovská
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
清晰细胞肾细胞癌(ccRCC)是肾细胞癌的最常见变异类型。它是一种侵袭性疾病,预后不良。ccRCC肿瘤微环境(TME)中存在丰富的免疫浸润物,产生各种信号分子,特别是细胞因子,主要激活Jak/STAT途径,对肿瘤发病过程产生显著影响。STAT3具有良好定义的致癌特性。我们使用多重分析和ELISA方法,测量了16例组织学验证的ccRCC患者肿瘤和健康肾组织中27种细胞因子和STAT3的浓度。我们在肿瘤组织中检测到G-CSF、IL-6、CXCL10、CCL3和CCL4的水平显著高于它们在健康对照组织中的水平。在不同核级(NG)的肿瘤之间,IL-1β和PDGF-BB的水平存在显著差异。肿瘤内IL-12p70和IL-15与肿瘤内STAT3呈显著正相关。肿瘤中STAT3的浓度显著低于肾脏。肿瘤中STAT3水平的增加与疾病的病理分期(TNM)增加相关,但与NG无关。我们的研究结果证实了各种细胞因子和STAT3在ccRCC发病机制中的显著作用,并显示了它们的临床相关性。
Clear cell renal cell carcinoma (ccRCC) is the most common variant of RCC. It is an aggressive disease with an unfavorable prognosis. The rich immune infiltrates present in the tumor microenvironment (TME) of ccRCC produce various signaling molecules, especially cytokines, which primarily activate the Jak/STAT pathway and significantly influence tumor pathogenesis. STAT3 has a well-defined oncogenic character. Using multiplex assays and ELISA, we have measured the concentrations of 27 cytokines and STAT3 in tumor and healthy renal tissue from 16 patients with histologically verified ccRCC. We have detected significantly higher levels of G-CSF, IL-6, CXCL10, CCL3, and CCL4 in tumor tissue than in their healthy counterparts. There were significant differences in the levels of IL-1β and PDGF-BB between tumors of different nuclear grades (NG). Intratumoral IL-12p70 and IL-15 showed a significant positive correlation with intratumoral STAT3. The concentration of STAT3 in tumors was significantly lower than in the kidney. An increase in tumor STAT3 levels was associated with an increase in the pathological stage of the disease (TNM), but not with NG. The results of our study confirm the significant role of various cytokines and STAT3 in the pathogenesis of ccRCC and indicate their clinical relevance.