Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Urol Oncol. 2019 May;37(5):299.e7-299.e18. doi: 10.1016/j.urolonc.2019.01.001. Epub 2019 Jan 17.
Metabolic adaptation in cancer cells is important for cancer cell survival. Alternation in cellular metabolism getting more energy to support cell proliferation played a critical role in disease progression. We initially analyzed the public transcriptome of urothelial carcinoma in Gene Expression Omnibus database (GSE31684) with particular focus on genes associated with carbohydrate metabolism, and found that Chitinase 3-like-1 (CHI3L1) was a significantly up-regulated gene associated with advanced disease status. This study was aimed to evaluate the expression and prognostic significance of CHI3L1 in upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC).
We performed immunohistochemical study to evaluate CHI3L1 expression in 2 well-defined cohorts of urothelial carcinoma, including UTUC (n = 340) and UBUC (n = 295). CHI3L1 expression level was determined by H-score method. The associations between CHI3L1 expression and clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MFS) were analyzed.
High expression of CHI3L1 was significantly associated with adverse clinicopathological features in UTUC or UBUC, including advanced tumor status (pT), nodal metastasis, high histological grade, vascular invasion, perineural invasion, and high mitotic activity (all P < 0.05). Kaplan-Meier survival analysis revealed that patients with high CHI3L1 expression had shorter DSS and MFS in both UTUC and UBUC (all P < 0.05). In multivariate survival analyses, high expression of CHI3L1 acted as an independent prognostic factor for worse DSS (P < 0.001 in UTUC and P = 0.036 in UBUC) and MFS (P = 0.002 in UTUC and P = 0.003 in UBUC) in both UTUC and UBUC groups.
High expression of CHI3L1 was significantly associated with aggressive clinicopathological features and acted as an independent prognostic factor for worse outcome in urothelial carcinoma.
癌细胞的代谢适应对于癌细胞的存活很重要。细胞代谢的改变以获取更多的能量来支持细胞增殖，在疾病进展中起着关键作用。我们最初在基因表达综合数据库（GSE31684）中分析了尿路上皮癌的公共转录组，特别关注与碳水化合物代谢相关的基因，发现几丁质酶 3 样蛋白 1（CHI3L1）是与疾病进展相关的显著上调基因。本研究旨在评估 CHI3L1 在上尿路上皮癌（UTUC）和膀胱尿路上皮癌（UBUC）中的表达及其预后意义。
我们进行了免疫组织化学研究，评估了 2 个明确的尿路上皮癌队列中 CHI3L1 的表达，包括 UTUC（n=340）和 UBUC（n=295）。通过 H 评分法确定 CHI3L1 的表达水平。分析 CHI3L1 表达与临床病理特征、疾病特异性生存率（DSS）和无转移生存率（MFS）的关系。
CHI3L1 的高表达与 UTUC 或 UBUC 的不良临床病理特征显著相关，包括肿瘤分期较晚（pT）、淋巴结转移、高组织学分级、血管侵犯、神经周围侵犯和高有丝分裂活性（均 P<0.05）。Kaplan-Meier 生存分析显示，CHI3L1 高表达的患者在 UTUC 和 UBUC 中 DSS 和 MFS 均较短（均 P<0.05）。多因素生存分析显示，CHI3L1 高表达是 UTUC 患者 DSS 更差的独立预后因素（P<0.001）和 UBUC 患者 MFS 更差的独立预后因素（P=0.036）。
CHI3L1 的高表达与侵袭性临床病理特征显著相关，是 UTUC 和 UBUC 患者预后不良的独立预后因素。
