Serum TFF3 may be a pharamcodynamic marker of responses to chemotherapy in gastrointestinal cancers

BMC Clinical Pathology

Bayasi Guleng²  Jian-Lin Ren¹  Chuan-Xing Xiao¹  Yun-Peng Liu¹  Li Xiao¹ 

[1] Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, 201 Hubin South Road, Xiamen 361004, Fujian Province, China;Faculty of Clinical Medicine, Medical College of Xiamen University, Xiangan South Road, Xiangan District, Xiamen 361102, Fujian Province, China

关键词: Biomarker;    TFF3;    Colorectal cancer;    Gastric cancer;   

Others  :  848348
DOI  :  10.1186/1472-6890-14-26

 received in 2013-06-13, accepted in 2014-06-10,  发布年份 2014

【 摘 要 】

Background

As a secreted protein, serum trefoil factor 3 (TFF3) has been reported to be a biomarker of several malignancies. We further investigated whether TFF3 can be applied as a biomarker for and predictor of responses to chemotherapy in gastrointestinal cancer.

Methods

Serum and urine samples were collected from 90 patients with gastric cancer, 128 patients with colorectal cancer and 91 healthy individuals. Serum and urine TFF3 levels were measured using an ELISA.

Results

Serum and urine TFF3 levels were significantly higher in the patients with gastric and colorectal cancer compared with the healthy individuals (P < 0.05). Higher serum levels of TFF3 were significantly correlated with distant metastasis and an advanced stage in the two types of cancer (P < 0.05). Age and the number of lymph node metastases were significantly correlated with serum TFF3 levels in colorectal cancer, and decreased serum TFF3 levels were significantly correlated with responses to chemotherapy in both the gastric and the colorectal cancer partial response (PR) groups. A combination of serum and urine data did not significantly improve the detection of either cancer, although urine levels have shown a significant negative relationship with the glomerular filtration rate (GFR).

Conclusions

Our data indicate that TFF3 may be an effective biomarker of tumor stage and the presence of distant metastasis, and may be a pharmacodynamic marker of response to chemotherapy in gastrointestinal cancer.

【 授权许可】

   
2014 Xiao et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55:74-108.
• [2]Shin HR: Global activity of cancer registries and cancer control and cancer incidence statistics in Korea. J Prev Med Public Health 2008, 41:84-91.
• [3]de Wit M, Fijneman RJA, Verheul HMW, Meijer GA, Jimenez CR: Proteomics in colorectal cancer translational research: biomarker discovery for clinical applications. Clin Biochem 2013, 46:466-479.
• [4]Chan MWY, Chan VYW, Leung WK, Chan KK, To KF, Sung JJY: Anti-sense trefoil factor family-3 (intestinal trefoil factor) inhibits cell growth and induces chemosensitivity to adriamycin in human gastric cancer cells. Life Sci 2005, 76:2581-2592.
• [5]Wright NA, Poulsom R, Stamp G, Van Noorden S, Sarraf C, Elia G: Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. Gastroenterology 1993, 104:12-20.
• [6]May FE, Westley BR: Trefoil proteins: their role in normal and malignant cells. J Pathol 1997, 183:4-7.
• [7]Peitz U, Wiede A, Guenther T, Ebert M, Hoffmann W, Malfertheiner P: TFF3 in esophageal, gastric mucosa as well as in gastric juice. Gastroenterology 2000, 118:A1291.
• [8]Im S, Yoo C, Jung JH, Choi HJ, Yoo J, Kang CS: Reduced expression of TFF1 and increased expression of TFF3 in gastric cancer: correlation with clinicopathological parameters and prognosis. Int J Med Sci 2013, 10:133-140.
• [9]Kannan N, Kang J, Kong X, Tang J, Perry JK, Mohankumar KM: Trefoil factor 3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Neoplasia 2010, 12:1041-1053.
• [10]Perry JK, Kannan N, Grandison PM, Mitchell MD, Lobie PE: Are trefoil factors oncogenic? Trends Endocrinol Metabol 2008, 19:74-81.
• [11]Makridakis M, Vlahou A: Secretome proteomics for discovery of cancer biomarkers. J Proteome 2010, 73:2291-2305.
• [12]Lacroix M: Significance, detection and markers of disseminated breast cancer cells. Endocr Relat Cancer 2006, 13:1033-1067.
• [13]Aikou S, Ohmoto Y, Gunji T, Matsuhashi N, Ohtsu H, Miura H: Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology 2011, 141:837-845.
• [14]Walker G, MacLeod K, Williams AR, Cameron DA, Smyth JF, Langdon SP: Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer. Gynecol Oncol 2007, 106:461-468.
• [15]Qu Y, Yang Y, Ma D, Xiao W: Increased trefoil factor 3 levels in the serum of patients with three major histological subtypes of lung cancer. Oncol Rep 2012, 27:1277-1283.
• [16]Bignotti E, Ravaggi A, Tassi RA, Calza S, Rossi E, Falchetti M: Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas. Br J Cancer 2008, 99:768-773.
• [17]Camargo MC, Goto Y, Zabaleta J, Morgan DR, Correa P, Rabkin CS: Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2012, 21:20-38.
• [18]Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009, 45:228-247.
• [19]Bellenir K: Cancer sourcebook : basic consumer health information about major forms and stages of cancer, featuring facts about head and neck cancers, lung cancers, gastrointestinal cancers, genitourinary cancers, lymphomas, blood cell cancers, endocrine cancers, skin cancers, bone cancers, metastatic cancers, and more; along with facts about cancer treatments, cancer risks and prevention. 6th edition. Detroit, MI: Omnigraphics; 2011.
• [20]Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001, 345:725-730.
• [21]Rustgi AK: The genetics of hereditary colon cancer. Genes Dev 2007, 21:2525-2538.
• [22]May M: From cells, secrets of the secretome leak out. Nat Med 2009, 15:828.
• [23]Kulasingam V, Diamandis EP: Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat Clin Pract Oncol 2008, 5:588-599.
• [24]May FE: The potential of trefoil proteins as biomarkers in human cancer. Biomark Med 2012, 6:301-304.
• [25]Meng JR, Tang HZ, Zhou KZ, Shen WH, Guo HY: TFF3 and survivin expressions associate with a lower survival rate in gastric cancer. Clin Exp Med 2013, 13:297-303.
• [26]Vestergaard EM, Borre M, Poulsen SS, Nexo E, Torring N: Plasma levels of trefoil factors are increased in patients with advanced prostate cancer. Clin Cancer Res 2006, 12:807-812.
• [27]Ahmed AR, Griffiths AB, Tilby MT, Westley BR, May FE: TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease. Am J Pathol 2012, 180:904-916.
• [28]Yamachika T, Werther JL, Bodian C, Babyatsky M, Tatematsu M, Yamamura Y: Intestinal trefoil factor: a marker of poor prognosis in gastric carcinoma. Clin Cancer Res 2002, 8:1092-1099.
• [29]Kaise M, Miwa J, Tashiro J, Ohmoto Y, Morimoto S, Kato M: The combination of serum trefoil factor 3 and pepsinogen testing is a valid non-endoscopic biomarker for predicting the presence of gastric cancer: a new marker for gastric cancer risk. J Gastroenterol 2011, 46:736-745.
• [30]Yamada A, Hoteya S, Iizuka T, Kaise M: Endoscopic resection of early gastric cancer. Nihon Rinsho 2012, 70:1778-1782.
• [31]Samson MH, Nexo E: Validation of commercial assays for measurements of trefoil factor family peptides in serum. Clin Chem Lab Med 2011, 49:2057-2060.
• [32]Levey AS, Stevens LA: Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 2010, 55:622-627.
• [33]Yu Y, Jin H, Holder D, Ozer JS, Villarreal S, Shughrue P: Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol 2010, 28:470-477.
• [34]Marrer E, Dieterle F: Impact of biomarker development on drug safety assessment. Toxicol Appl Pharmacol 2010, 243:167-179.
• [35]Dieterle F, Sistare F, Goodsaid F, Papaluca M, Ozer JS, Webb CP: Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol 2010, 28:455-462.
• [36]Blomme EA: Assessing renal function: some significant improvements on the horizon. Vet J 2011, 188:128-129.