Expression of Obesity Hormone Leptin in Human Colorectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Chunsheng ¹ , CONG Jinchun ¹ , SHEN Mingyang ² , WANG Junjiang ³ , ZHANG Hong ¹ , QIAO Lei ¹

1.Department of Colorectal and Anal Surgery,Shengjing Hospital,China Medical University,Shenyang 110004,China;;
2.Department of Gastrointestinal Surgery,The 4th Affiliated Hospital,China Medical University,Shenyang 110032,China;;
3.Department of Anorectal Surgery,Affiliated Hospital of Liaoning Traditional Chinese Medical University,Shenyang 110032,China;

Corresponding author：

Keywords：

Colorectal cancer; Leptin; p53; K-ras; Adenomatous polyposis coli gene; Delete in colorectal carcinoma gene

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Objective To evaluate the relationship between leptin level in serum and clinicopathologic features of colorectal cancer. Methods ABC-ELLSA was used to detect the leptin level in 30 cases of colorectal cancer without dystrophy (cancer group) and 24 normal controls (control group). The expressions of K-ras， p53， adenomatous polyposis coli （APC） gene and delete in colorectal carcinoma gene (DCC) mRNA of the tumor were examined by RT-PCR, the levels of serum CEA and CA19-9, and other clinicopathologic features were also recorded. Results The leptin level in cancer group 〔（3.53±1.72） μg/L〕 was higher than that in control group 〔（2.27±1.01） μg/L〕, P＜0.05, and the difference was independent on gender. There were no significant differences of leptin level in different tumor stages and different tumor location （P gt;0.05）. Leptin level of poorly differentiated tumor was obviously lower than that of well differentiated and moderately differentiated tumor （P＜0.05）. There were no associations between leptin level and the levels of CEA and CA19-9, likewise there were no associations between leptin level and the expressions of K-ras, p53, APC and DCC in tumor （P gt;0.05）. Conclusion The leptin level of colorectal cancer patient is higher than that of normal person, which is affected by the differentiation of tumor. But there are no significant correlations between the level of leptin in serum and TNM stage, tumor location, tumor markers of serum, K-ras, p53, APC or DCC in tumor.

Citation： CHEN Chunsheng,CONG Jinchun,SHEN Mingyang,WANG Junjiang,ZHANG Hong,QIAO Lei. Expression of Obesity Hormone Leptin in Human Colorectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(5): 379-383. doi: Copy

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16.	Tessitore L, Vizio B, Jenkins O, et al. Leptin expression in colorectal and breast cancer patients [Ｊ]. Int J Mol Med, 2000; 5(4): 421-426.
17.	Hong SJ, Kwon KW, Kim SG, et al. Variation in expression of gastric leptin according to differentiation and growth pattern in gastric adenocarcinoma [Ｊ]. Cytokine, 2006; 33(2): 66-71.
18.	Grosfeld A, Andre J, Hauguel-De Mouzon S, et al. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter [Ｊ]. J Biol Chem, 2002; 277(45): 42953-42957.
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22.	Aparicio T, Guilmeau S, Goiot H, et al. Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa [Ｊ]. Gastroenterology, 2004; 126(2): 499-510.
23.	Ealey KN, Lu S, Archer MC. Development of aberrant crypt foci in the colons of ob/ob and db/db mice: evidence that leptin is not a promoter [Ｊ]. Mol Carcinog, 2008; 47(9): 667-677.
24.	张珊，陈国庆，唐鸿波, 等. 血清胰岛素样生长因子-1 对癌性恶病质小鼠营养状况的影响 [Ｊ]. 中国普外基础与临床杂志， 2008; 15（2）： 112-115.
25.	王治国, 杨喆, 秦环龙. 术前口服碳水化合物改善术后胰岛素抵抗的作用及其机理研究 [Ｊ]. 中国普外基础与临床杂志， 2008; 15（11）： 799-804.

1. Frezza EE, Wachtel MS, Chiriva-Internati M. Influence of obesity on the risk of developing colon cancer [Ｊ]. Gut, 2006; 55(2): 285-291.
2. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue [Ｊ]. Nature, 1994; 372(6505): 425-432.
3. Sauter ER, Garofalo C, Hewett J, et al. Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer [Ｊ]. Horm Metab Res, 2004; 36(5): 336-340.
4. Garofalo C, Surmacz E. Leptin and cancer [Ｊ]. J Cell Physiol, 2006; 207(1): 12-22.
5. Hardwick JC, Van Den Brink GR, Offerhaus GJ, et al. Leptin is a growth factor for colonic epithelial cells [Ｊ]. Gastroenterology, 2001; 121(1): 79-90.
6. Aparicio T, Kotelevets L, Tsocas A, et al. Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in Apc(Min/+) mice [Ｊ]. Gut, 2005; 54(8): 1136-1145.
7. Falk RT, Brinton LA, Madigan MP, et al. Interrelationships between serum leptin, IGF-1, IGFBP3, C-peptide and prolactin and breast cancer risk in young women [Ｊ]. Breast Cancer Res Treat, 2006; 98(2): 157-165.
8. Stattin P, Sderberg S, Hallmans G, et al. Leptin is associated with increased prostate cancer risk: a nested case-referent study [Ｊ]. J Clin Endocrinol Metab, 2001; 86(3): 1341-1345.
9. Kondrup J, Allison SP, Elia M, et al. ESPEN guidelines for nutrition screening 2002 [Ｊ]. Clin Nutr, 2003; 22(4): 415-421.
10. Wallace AM, Sattar N, McMillan DC. Effect of weight loss and the inflammatory response on leptin concentrations in gastrointestinal cancer patients [Ｊ]. Clin Cancer Res, 1998; 4(12): 2977-2979.
11. Ma Z, Gingerich RL, Santiago JV, et al. Radioimmunoassay of leptin in human plasma [Ｊ]. Clin Chem, 1996; 42(6 Pt 1): 942-946.
12. Stattin P, Lukanova A, Biessy C, et al. Obesity and colon cancer: does leptin provide a link? [Ｊ]. Int J Cancer, 2004; 109(1): 149-152.
13. Tamakoshi K, Toyoshima H, Wakai K, et al. Leptin is associated with an increased female colorectal cancer risk: a nested case-control study in Japan [Ｊ]. Oncology, 2005; 68(4-6): 454-461.
14. Stattin P, Palmqvist R, Sderberg S, et al. Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden [Ｊ]. Oncol Rep, 2003; 10(6): 2015-2021.
15. Bolukbas FF, Kilic H, Bolukbas C, et al. Serum leptin concentration and advanced gastrointestinal cancers: a case controlled study [Ｊ]. BMC Cancer, 2004; 4: 29.
16. Tessitore L, Vizio B, Jenkins O, et al. Leptin expression in colorectal and breast cancer patients [Ｊ]. Int J Mol Med, 2000; 5(4): 421-426.
17. Hong SJ, Kwon KW, Kim SG, et al. Variation in expression of gastric leptin according to differentiation and growth pattern in gastric adenocarcinoma [Ｊ]. Cytokine, 2006; 33(2): 66-71.
18. Grosfeld A, Andre J, Hauguel-De Mouzon S, et al. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter [Ｊ]. J Biol Chem, 2002; 277(45): 42953-42957.
19. Koda M, Sulkowska M, Wincewicz A, et al. Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer [Ｊ]. Ann N Y Acad Sci, 2007; 1095: 90-98.
20. Chaudhary M, Mandir N, FitzGerald AJ, et al. Starvation, leptin and epithelial cell proliferation in the gastrointestinal tract of the mouse [Ｊ]. Digestion, 2000; 61(4): 223-229.
21. Hirose Y, Hata K, Kuno T, et al. Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice [Ｊ]. Carcinogenesis, 2004; 25(5): 821-825.
22. Aparicio T, Guilmeau S, Goiot H, et al. Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa [Ｊ]. Gastroenterology, 2004; 126(2): 499-510.
23. Ealey KN, Lu S, Archer MC. Development of aberrant crypt foci in the colons of ob/ob and db/db mice: evidence that leptin is not a promoter [Ｊ]. Mol Carcinog, 2008; 47(9): 667-677.
24. 张珊，陈国庆，唐鸿波, 等. 血清胰岛素样生长因子-1 对癌性恶病质小鼠营养状况的影响 [Ｊ]. 中国普外基础与临床杂志， 2008; 15（2）： 112-115.
25. 王治国, 杨喆, 秦环龙. 术前口服碳水化合物改善术后胰岛素抵抗的作用及其机理研究 [Ｊ]. 中国普外基础与临床杂志， 2008; 15（11）： 799-804.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Obesity Hormone Leptin in Human Colorectal Cancer

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