Park Jee Soo, Jang Won Sik, Kim Jongchan, Lee Seung Hwan, Rha Koon Ho, Ham Won Sik
Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Cancer Metab. 2021 Apr 6;9(1):15. doi: 10.1186/s40170-021-00251-y.
Visceral fat produces several hormones and cytokines associated with carcinogenesis and tumor progression. Herein, we investigated the association between visceral adiposity and target-gene mRNA expression in patients with localized small clear-cell renal-cell carcinoma (ccRCC).
We included 200 patients with localized clinical T1a stage ccRCC who had undergone nephrectomy from November 2018 to November 2020 in a prospective clinical trial (NCT03694912). Visceral, subcutaneous, and total adipose tissue in these patients was measured via preoperative computerized tomography of the mid-third lumbar vertebra region. We then examined the association between adiposity and the mRNA levels of PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, BAIAP2L1, and TMEM38B in matched frozen tumor tissues and plasma samples.
Upon the stratification of patients into quartiles according to their relative visceral adiposity, high visceral adiposity was found to be significantly associated with low ISUP grade (P = 0.004). Multivariate logistic regression analysis revealed a significant association between frozen tissue DDX11 expression and high visceral adiposity (OR 0.676, 95% CI 0.587-0.779, P < 0.001). Moreover, frozen tissue DDX11 expression was significantly associated with high ISUP grade (OR 1.556, 95% CI 1.223-1.981, P < 0.001). The frozen tissue mRNA expression of DDX11 was identified as a biomarker for visceral adiposity and cancer aggressiveness.
The results obtained herein will aid in inferring the aggressiveness of small ccRCCs, represented by ISUP nuclear grade, in clinical practice. Our findings indicated that DDX11 and visceral fat play active roles in small ccRCC. These roles should be examined in future studies for the possible use of DDX11 and visceral fat as prognostic biomarkers in the treatment of patients with ccRCC.
ClinicalTrials.gov , NCT03694912 , Registered 3 October 2018.
内脏脂肪会产生多种与致癌作用和肿瘤进展相关的激素和细胞因子。在此，我们研究了局限性小细胞透明肾细胞癌（ccRCC）患者内脏肥胖与靶基因mRNA表达之间的关联。
我们纳入了2018年11月至2020年11月期间在一项前瞻性临床试验（NCT03694912）中接受肾切除术的200例局限性临床T1a期ccRCC患者。通过术前对第三腰椎中部区域进行计算机断层扫描来测量这些患者的内脏、皮下和总脂肪组织。然后，我们在匹配的冷冻肿瘤组织和血浆样本中检测肥胖与PBRM1、BAP1、SETD2、KDM5C、FOXC2、CLIP4、AQP1、DDX11、BAIAP2L1和TMEM38B的mRNA水平之间的关联。
根据患者的相对内脏肥胖程度将其分为四分位数后，发现高内脏肥胖与低国际泌尿病理学会（ISUP）分级显著相关（P = 0.004）。多因素逻辑回归分析显示，冷冻组织中DDX11表达与高内脏肥胖之间存在显著关联（比值比[OR] 0.676，95%置信区间[CI] 0.587 - 0.779，P < 0.001）。此外，冷冻组织中DDX11表达与高ISUP分级显著相关（OR 1.556，95% CI 1.223 - 1.981，P < 0.001）。冷冻组织中DDX11的mRNA表达被确定为内脏肥胖和癌症侵袭性的生物标志物。
本文获得的结果将有助于在临床实践中推断以ISUP核分级为代表的小ccRCC的侵袭性。我们的研究结果表明，DDX11和内脏脂肪在小ccRCC中发挥着积极作用。在未来的研究中应检查这些作用，以便可能将DDX11和内脏脂肪用作ccRCC患者治疗中的预后生物标志物。
ClinicalTrials.gov，NCT03694912，2018年10月3日注册。
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