Suppressor of cytokine signaling 3 (SOCS3) is not an independent biomarker of colorectal adenoma risk

被引：3
作者：
Hamilton K.E. [1 ]
Lund P.K. [1 ]
Galanko J.A. [2 ]
Sandler R.S. [2 ]
Keku T.O. [2 ]
机构：
[1] Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7545
[2] Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7545
来源：
BMC Research Notes | / 3卷 / 1期
基金：
美国国家卫生研究院;
关键词：
Adenoma; Normal Mucosa; Colorectal Adenoma; Colorectal Adenoma Risk; North Carolina Hospital;
D O I：
10.1186/1756-0500-3-144
中图分类号：
学科分类号：
摘要：
Background: Inflammation and its associated pathologies are increasingly suggested as risk factors for colorectal cancer (CRC) development. Previous research from our group has shown that increased levels of circulating, pro-inflammatory cytokines IL-6 and TNF promote colorectal adenoma risk. Emerging data in mice and humans suggest that Suppressor of Cytokine Signaling 3 (SOCS3) may act as a tumor suppressor in the intestine, and decreased SOCS3 expression may promote CRC. As SOCS3 has been shown to inhibit the actions of IL-6 and TNF in the intestine, we hypothesized that decreased SOCS3 expression in normal mucosa may predispose to adenomas and thus increase risk for CRC. Findings: We examined SOCS3 mRNA levels in normal mucosa biopsies of 322 screening colonoscopy patients (93 with adenoma and 229 without adenoma) using real-time qRT-PCR. Logistic regression analysis was used to generate odds ratios (OR) and 95% confidence intervals to determine if low SOCS3 expression was associated with adenoma status. Median SOCS3 values did not differ between patients with or without adenoma. Logistic regression analysis showed no association (unadjusted or adjusted for age and sex) between SOCS3 and colorectal adenomas. Conclusions: Low SOCS3 mRNA expression is not an independent biomarker of colorectal adenoma risk in the normal mucosa. SOCS3 silencing likely occurs later in CRC progression. © 2010 Keku et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 19 条
  • [1] Rigby R.J., Simmons J.G., Greenhalgh C.J., Alexander W.S., Lund P.K., Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon, Oncogene, 26, pp. 4833-4841, (2007)
  • [2] Li Y., De Haar C., Chen M., Deuring J., Gerrits M.M., Smits R., Xia B., Kuipers E.J., Der Van J.W.C., Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis, Gut, 59, pp. 227-235
  • [3] He B., You L., Uematsu K., Zang K., Xu Z., Lee A.Y., Costello J.F., McCormick F., Jablons D.M., SOCS-3 is frequently silenced by hypermethylation and suppresses cell growth in human lung cancer, Proceedings of the National Academy of Sciences of the United States of America, 100, pp. 14133-14138, (2003)
  • [4] Niwa Y., Kanda H., Shikauchi Y., Saiura A., Matsubara K., Kitagawa T., Yamamoto J., Kubo T., Yoshikawa H., Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma, Oncogene, 24, pp. 6406-6417, (2005)
  • [5] Weber A., Hengge U.R., Bardenheuer W., Tischoff I., Sommerer F., Markwarth A., Dietz A., Wittekind C., Tannapfel A., SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition, Oncogene, 24, pp. 6699-6708, (2005)
  • [6] Kim S., Keku T.O., Martin C., Galanko J., Woosley J.T., Schroeder J.C., Satia J.A., Halabi S., Sandler R.S., Circulating levels of inflammatory cytokines and risk of colorectal adenomas, Cancer Res, 68, pp. 323-328, (2008)
  • [7] Suzuki A., Hanada T., Mitsuyama K., Yoshida T., Kamizono S., Hoshino T., Kubo M., Yamashita A., Okabe M., Takeda K., Et al., CIS3/SOCS3/SSI3 Plays a Negative Regulatory Role in STAT3 Activation and Intestinal Inflammation, The Journal of Experimental Medicine, 193, pp. 471-482, (2001)
  • [8] Croker B.A., Krebs D.L., Zhang J.G., Wormald S., Willson T.A., Stanley E.G., Robb L., Greenhalgh C.J., Forster I., Clausen B.E., Et al., SOCS3 negatively regulates IL-6 signaling in vivo, Nature Immunology, 4, pp. 540-545, (2003)
  • [9] Wang L., Walia B., Evans J., Gewirtz A.T., Merlin D., Sitaraman S.V., IL-6 Induces NF-kB Activation in the Intestinal Epithelia, The Journal of Immunology, 171, pp. 3194-3201, (2003)
  • [10] Onizawa M., Nagaishi T., Kanai T., K-I N., Oshima S., Nemoto Y., Yoshioka A., Totsuka T., Okamoto R., Nakamura T., Et al., Signaling pathway via TNF-{alpha}/NF-{kappa}B in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis, Am J Physiol Gastrointest Liver Physiol, 296, pp. 7850-859, (2009)
12