Dai X, Wang F, DU Y Q, Song Y X, Xu T
Department of Urology, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Aug 18;54(4):605-614. doi: 10.19723/j.issn.1671-167X.2022.04.005.
To investigate the correlation between expression levels of adipokine and clinicopathological features and prognosis of patients with upper tract urothelial carcinoma (UTUC) based on immunohistochemical staining and bioinformatics analysis.
The 8 adipokines in this study included adiponectin (AdipoQ), leptin (LEP), interleukin (IL)-6, IL-10 and their receptors (AdipoR1, AdipoR2, LEPR, IL-6R, IL-10RA, IL-10RB). Tissue samples of patients with UTUC who underwent surgical treatment in Peking University People's Hospital from January 2014 to April 2021 were selected for immunohistochemical staining. Their quantitative gene expression data were calculated by H-Score, and relevant clinical and follow-up data were collected retrospectively. Transcription group sequencing data of UTUC patients in Gene Expression Omnibus database (GSE134292 dataset) were downloaded for comparison. Chi-square test or -test was used to compare the expression level of adipokine between non-muscle invasive group and muscle invasive group. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were utilized to analyze independent predictors of overall survival (OS), disease-free survival (DFS), intravesical recurrence-free survival (IVRFS) in the both cohorts. The < 0.05 was considered statistically significant.
In the study, 63 tissue samples of the patients with UTUC who underwent surgical treatment in Peking University People's Hospital and 57 UTUC patients in GSE134292 dataset were selected. In immunohistochemical cohort, the expressions of AdipoQ (=0.003 6), AdipoR1 (=0.006 5), LEP (=0.007 7), IL-10 (=0.006 9), and IL-10RA (=0.008 9) were statistically higher in muscle invasive group. In GSE134292 cohort, the expressions of AdipoR1 (=0.000 4), AdipoR2 (=0.000 4), IL-6 (=0.005 0), IL-10 (=0.001 7), and IL-10RA (=0.008 1) were statistically higher in muscle invasive group. Kaplan-Meier survival curve and multivariate Cox regression analysis showed that high IL-10RA expression was an independent predictive factor of IVRFS (=0.044, =0.996, 95%: 0.992-0.998) in immunohistochemical cohort, which was confirmed in GSE134292 cohort (=0.014, =0.515, 95%: 0.304-0.873).
The expression levels of AdipoQ, AdipoR1, IL-10, and IL-10RA were correlated with tumor stage, suggesting that these adipokines played important roles in tumor progression. IL-10RA was an independent predictor of IVRFS, suggesting that IL-10 and its receptor played a critical role in tumor recurrence.
基于免疫组织化学染色和生物信息学分析，探讨脂肪因子表达水平与上尿路尿路上皮癌（UTUC）患者临床病理特征及预后的相关性。
本研究中的8种脂肪因子包括脂联素（AdipoQ）、瘦素（LEP）、白细胞介素（IL）-6、IL-10及其受体（AdipoR1、AdipoR2、LEPR、IL-6R、IL-10RA、IL-10RB）。选取2014年1月至2021年4月在北京大学人民医院接受手术治疗的UTUC患者的组织样本进行免疫组织化学染色。通过H评分计算其定量基因表达数据，并回顾性收集相关临床和随访数据。下载基因表达综合数据库（GSE134292数据集）中UTUC患者的转录组测序数据进行比较。采用卡方检验或t检验比较非肌层浸润组和肌层浸润组脂肪因子的表达水平。采用单因素和多因素Cox回归分析以及Kaplan-Meier生存曲线分析两组患者总生存（OS）、无病生存（DFS）、膀胱内无复发生存（IVRFS）的独立预测因素。P<0.05认为差异有统计学意义。
本研究选取了63例在北京大学人民医院接受手术治疗的UTUC患者的组织样本以及GSE134292数据集中的57例UTUC患者。在免疫组织化学队列中，肌层浸润组中AdipoQ（P=0.003 6）、AdipoR1（P=0.006 5）、LEP（P=0.007 7）、IL-10（P=0.006 9）和IL-10RA（P=0.008 9）的表达在统计学上更高。在GSE134292队列中，肌层浸润组中AdipoR1（P=0.000 4）、AdipoR2（P=0.000 4）、IL-6（P=0.005 0）、IL-10（P=0.001 7）和IL-10RA（P=0.008 1）的表达在统计学上更高。Kaplan-Meier生存曲线和多因素Cox回归分析显示，在免疫组织化学队列中，高IL-10RA表达是IVRFS的独立预测因素（P=0.044，HR=0.996，95%CI：0.992-0.998），这在GSE134292队列中得到证实（P=0.014，HR=0.515，95%CI：0.304-0.873）。
AdipoQ、AdipoR1、IL-10和IL-10RA的表达水平与肿瘤分期相关，提示这些脂肪因子在肿瘤进展中起重要作用。IL-10RA是IVRFS的独立预测因素，提示IL-10及其受体在肿瘤复发中起关键作用。
