Yang Liu, Liu Yidong, An Huimin, Chang Yuan, Zhang Weijuan, Zhu Yu, Xu Le, Xu Jiejie
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Urology, Shanghai Cancer Center, Fudan University, Shanghai, China.
Ann Surg Oncol. 2016 Mar;23(3):1044-52. doi: 10.1245/s10434-015-4911-7. Epub 2015 Oct 14.
Colony-stimulating factor 1 receptor (CSF-1R), a single-pass type III transmembrane tyrosine-protein kinase, is mainly involved in inflammation and immune regulation to facilitate the progression of solid tumors. This study aimed to evaluate the impact of CSF-1R expression on clinical outcome of patients with clear cell renal cell carcinoma (ccRCC) after surgery.
We retrospectively enrolled 268 patients with ccRCC undergoing nephrectomy between 2001 and 2004. Clinicopathologic features and cancer-specific survival (CSS) were collected. Western blot analysis was performed in the pairwise comparisons of CSF-1R expression in peritumor and tumor tissues of patients with ccRCC. Immunohistochemistry was conducted to determine CSF-1R expression level in tumor specimens. Survival analysis was performed by the Kaplan-Meier method. Cox regression models were used to evaluate the impact of prognostic factors on CSS. A concordance index was calculated to measure prognostic accuracy. A prognostic nomogram was constructed on the basis of the identified independent prognostic factors.
CSF-1R expression in tumor tissues was higher than in peritumor tissues in 71.4% (5 of 7) patients. CSF-1R expression of tumor tissues was positively associated with metastasis, tumor, node, metastasis classification system (TNM) stage, Eastern Cooperative Oncology Group performance status score and poor CSS. CSF-1R expression was determined as an independent prognostic factor for CSS in patients with ccRCC. Furthermore, extension of the well-established prognostic models with CSF-1R expression presented significantly improved prognostic accuracy. An efficient prognostic nomogram was constructed on the basis of the independent prognostic factors.
High CSF-1R expression is a potential independent adverse prognostic factor for CSS in patients with ccRCC.
集落刺激因子1受体(CSF-1R)是一种单次跨膜III型酪氨酸蛋白激酶,主要参与炎症和免疫调节,促进实体瘤进展。本研究旨在评估CSF-1R表达对透明细胞肾细胞癌(ccRCC)患者术后临床结局的影响。
我们回顾性纳入了2001年至2004年间接受肾切除术的268例ccRCC患者。收集临床病理特征和癌症特异性生存(CSS)情况。对ccRCC患者瘤周组织和肿瘤组织中CSF-1R表达进行配对比较,采用蛋白质印迹分析。进行免疫组织化学以确定肿瘤标本中CSF-1R表达水平。采用Kaplan-Meier法进行生存分析。使用Cox回归模型评估预后因素对CSS的影响。计算一致性指数以衡量预后准确性。基于确定的独立预后因素构建预后列线图。
71.4%(7例中的5例)患者肿瘤组织中CSF-1R表达高于瘤周组织。肿瘤组织中CSF-1R表达与转移、肿瘤-淋巴结-转移(TNM)分期、东部肿瘤协作组体能状态评分及不良CSS呈正相关。CSF-1R表达被确定为ccRCC患者CSS的独立预后因素。此外,将CSF-1R表达纳入成熟的预后模型可显著提高预后准确性。基于独立预后因素构建了有效的预后列线图。
高CSF-1R表达是ccRCC患者CSS的潜在独立不良预后因素。