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Int J Clin Exp Pathol 2013;6(9):1806-1816

Original Article
Assessing the role of IL-35 in colorectal cancer progression and prognosis

Jin-Cheng Zeng, Zhi Zhang, Tian-Yu Li, Yan-Fang Liang, Hong-Mei Wang, Jing-Jing Bao, Jun-Ai Zhang, Wan-Dang Wang, Wen-Yu Xiang, Bin
Kong, Zhi-Yong Wang, Bin-Hua Wu, Xiao-Dong Chen, Long He, Shu Zhang, Cong-Yi Wang, Jun-Fa Xu

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; Department of Surgery, Affiliated Hospital of Guangdong
Medical College, Zhangjiang 523001, China; Department of Surgery, Second Clinical Medical School of Guangdong Medical College,
Dongguan 523808, China; Department of Pathology, Taiping people’s Hospital of Dongguan, Dongguan 523905, China; The Center for
Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave. Wuhan
430030, China. Equal contributors.

Received June 19, 2013; Accepted July 29, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: 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. (IJCEP1306032).

Keywords: Interleukin-35, colorectal cancer, regulatory T cell, EBI3, IL-12p35

Address correspondence to: Dr. Jun-Fa Xu, Department of Clinical Immunology, Institute of Laboratory Medicine, Guangdong Medical College,
Dongguan, China, 523808. Tel: +86-769-22896378; +86-769-22896440; E-mail: imxujunfa@163.com