Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients

Abstract

In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine-rich α-2-glycoprotein, hemoglobin subunit β, Ig α-2 chain C region, and complement factor B as well as downregulated afamin, zinc-α-2-glycoprotein, vitronectin, and α-1-antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin-8, interferon gamma-induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma.

Afamin — A pleiotropic glycoprotein involved in various disease states

“…Most of these studies, however, await evaluation by quantitative analyses using appropriate methods in sufficiently large study groups [26][27][28][29][30][31][32][33]. Of these many studies, two may highlight the importance of proper validation studies after a potential tumor marker candidate has been discovered [29,33].…”

Afamin promotes glucose metabolism in papillary thyroid carcinoma

“…The functions of afamin have been investigated in epidemiologic studies, most of which were cancerrelated. Circulating afamin concentrations have been studied in various types of carcinomas including ovarian (Jackson et al, 2007), bladder , colorectal (Choi et al, 2013), gastric (Humphries et al, 1844), uterine cervix (Jeong et al, 2008), breast (Opstal-van Winden et al, 2011, as well as thyroid cancer (Song et al, 2013). In addition, recently it was found that afamin was strongly associated with the prevalence and development of metabolic syndrome (Kronenberg et al, 2014).…”

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

“…Since the cytokines play an essential role in the communication between tumor cell initiation/progression and host anti-tumor immunity (6)(7)(8)(9)(10)(11), it is important to investigate the cytokine changes in the tumor microenvironment, in order to better understand the transitional mechanisms and design novel interventional strategies. Indeed, in previous studies, we and others have revealed that the colorectal neoplastic transformation leads to a remarkable alteration of cytokine secretion in the tumor immune microenvironment (6,8,12,13), this may have a significant role in predicting the progression from the adenomas to CRCs (12,14,15) and prognosis of the CRCs (7,9,10,12,13,16).…”