Zeng Jin-Cheng, Zhang Zhi, Li Tian-Yu, Liang Yan-Fang, Wang Hong-Mei, Bao Jing-Jing, Zhang Jun-Ai, Wang Wan-Dang, Xiang Wen-Yu, Kong Bin, Wang Zhi-Yong, Wu Bin-Hua, Chen Xiao-Dong, He Long, Zhang Shu, Wang Cong-Yi, Xu Jun-Fa
Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College Dongguan, China, 523808 ; Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics Dongguan 523808, China.
Int J Clin Exp Pathol. 2013 Aug 15;6(9):1806-16. eCollection 2013.
Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.
尽管白细胞介素(IL)-35近期被发现与肿瘤发生有关,但其对结直肠癌(CRC)进展及预后的确切影响仍有待明确阐释。因此,在本报告中,我们对CRC患者与配对的对照受试者的IL-35水平进行了比较分析。IL-35在所有CRC组织中均高表达,在绝大多数结直肠癌细胞中均可检测到。CRC裂解物和血清样本中的IL-35水平与恶性程度及肿瘤临床分期高度相关。特别值得注意的是,手术切除后的患者血清IL-35显著降低,这表明IL-35促进CRC进展并与不良预后相关。机制研究表明,CRC患者血清IL-35水平与外周调节性T(Treg)细胞数量之间存在显著相关性,提示IL-35可能通过诱导Treg细胞参与CRC发病机制,而癌细胞来源的IL-35也可能将Treg细胞招募至肿瘤微环境中以促进肿瘤生长。总之,我们的数据支持IL-35可能是临床评估CRC进展和预后的有价值生物标志物。