Expression and Clinical Significance of Tumor Suppressor Gene KiSS-1 in Papillary Thyroid Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GAO Rongjun , WANG Nanpeng , YE Hui , GAO Qingjun , ZHOU Yan , DUAN Haisong , ZHAO Daiwei.

Department of Thyroid Surgery, The Affiliated Hospital of Guiyang Medical College, Guiyang 550004, China;

Corresponding author：

Keywords：

Papillary thyroid carcinoma; KiSS-1 protein; Metastin; Invasion; Metastasis; Immunohistochemistry

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Objective To detect the expression of KiSS-1 protein in papillary thyroid carcinoma, and to analyze its significance.
Methods Paraffin-embedded specimens of 32 patients with thyroid papillary carcinoma and its adjacent cancer tissues were included in this study. Then the expression of KiSS-1 protein was detected by munohistochemistry and its relationship with clinical pathological features was analyzed.
Results KiSS-1 protein mainly expressed in the cell membrane and cytoplasm. The expression of KiSS-1 protein was positive in adjacent tissues, but decreased or absent in cancer tissues in 32 patients. In the latter, there were 11 cases with positive expression (34.4%) and 21 cases with negative expression (65.6%), and the difference was statistically significant (χ2=31.256, P lt;0.001). The average value of KiSS-1 protein expression represented by absorbance (A) value (119.595 2) in cancer tissues was higher than that in adjacent tissues (174.805 0), t=34.429, P lt;0.001. The expression of KiSS-1 protein in cancer tissues was not related to patient gender (P=0.618) and age (P=0.061), but except TNM staging (P=0.034). The expression rate of KiSS-1 protein in cancer tissues with lymph node metastasis (4/4, 100%) was significantly higher than that without lymph node metastasis (7/28, 25.0%)， P=0.003.
Conclusion The expression of KiSS-1 protein is decreased or absent in papillary thyroid carcinoma, which may be involved in tumorigenesis, invasion, and metastasis.

Citation： GAO Rongjun,WANG Nanpeng,YE Hui,GAO Qingjun,ZHOU Yan,DUAN Haisong,ZHAO Daiwei.. Expression and Clinical Significance of Tumor Suppressor Gene KiSS-1 in Papillary Thyroid Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(8): 775-779. doi: Copy

1.	王雅辉, 叶晖, 王南鹏, 等. 抑癌基因TIP30在甲状腺乳头状癌中的表达与临床意义 [J]. 中国普外基础与临床杂志, 2009; 16(5): 356359.
2.	Lee JH, Welch DR. Identification of highly expressed gene in metastasissuppressed chronmosome 6/human malignant melanoma hybrid cells using subtractive hybridization and differential display [J]. Int J Cancer, 1997; 71(6): 10351044.
3.	Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? [J]. J Clin Invest, 1997; 99(9): 21522164.
4.	贺旭, 林建华. Kiss1与其受体GPR54在肿瘤转移中的作用 [J]. 中国医科大学学报, 2009; 8(4): 240244.
5.	Poussin K, Dienes H, Sirma H, et al. Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas [J]. Int J Cancer, 1999; 80(4): 497505.
6.	胡淑阳, 吴艺捷. 甲状腺癌相关基因的研究进展 [J]. 医学综述, 2009; 15(13): 19531956.
7.	陈燕昌, 陈大良, 殷凤峙. 甲状腺癌组织中肿瘤转移抑制基因的异常表达及其临床意义 [J]. 中国普外基础与临床杂志, 1996; 3(3): 143145.
8.	姜军, 韩晓蓉. 甲状腺癌的分子生物学研究进展 [J]. 中国普外基础与临床杂志, 2000; 7(5): 326327.
9.	Fidler IJ. Cancer bioligy: invasions and metastasis [A]. In: Abeloff MD, Armitage JO, Lichter AS, et al. Clinical Oncology [M]. 2nd eds. New York: Churchill Livingstone, 2000: 2953.
10.	孙治军, 姚榛祥. 表皮生长因子促进滤泡状和乳头状甲状腺癌增殖、转移和浸润的体内外试验 [J]. 中国普外基础与临床杂志, 1995; 2(3): 186, 157.
11.	Lee JH, Welch DR. Suppression of metastasis in human breast carcinoma MDAMB435 cells after transfection with the metastasis suppressor gene, KiSS1 [J]. Cancer Res, 1997; 57(12): 23842387.
12.	Welch DR, RinkerSchaeffer CW. What defines a useful marker of metastasis in human cancer? [J]. J Natl Cancer Inst, 1999; 91(16): 13511353.
13.	Yoshida BA, Sokoloff MM, Welch DR, et al. Metastasissuppressor genes: a review and perspective on an emerging field [J]. J Natl Cancer Inst, 2000; 92(21): 17171730.
14.	Lee JH, Miele ME, Hicks DJ, et al. KiSS1, a novel human malignant melanoma metastasissuppressor gene [J]. J Natl Cancer Inst, 1996; 88(23): 17311737.
15.	Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS1 encodes peptide ligand of a Gproteincoupled receptor [J]. Nature, 2001; 411(6837): 613617.
16.	Martin TA, Watkins G, Jiang WG. KiSS1 expression in human breast cancer [J]. Clin Exp Metastasis, 2005; 22(6): 503511.
17.	SanchezCarbayo M, Capodieci P, CordonCardo C. Tumor suppressor role of KiSS1 in bladder cancer: loss of KiSS1 expression is associated with bladder cancer progression and clinical outcome [J]. Am J Pathol, 2003; 162(2): 609617.
18.	Dhar DK, Naora H, Kubota H, et al. Downregulation of KiSS1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma [J]. Int J Cancer, 2004; 111(6): 868872.
19.	Ikeguchi M, Hirooka Y, Kaibara N. Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS1 and orphan Gproteincoupled receptor (hOT7T175) gene expression in hepatocellular carcinoma [J]. J Cancer Res Clin Oncol, 2003; 129(9): 531535.
20.	Masui T, Doi R, Mori T, et al. Metastin and its variant forms suppress migration of pancreatic cancer cells [J]. Biochem Biophys Res Commun, 2004; 315(1): 8592.
21.	Ikequchi M, Yamaquchi K, Kaibara N. Clinical significance of the loss of KiSS1 and orphan Gproteincoupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma [J]. Clin Cancer Res, 2004; 10(4): 13791383.
22.	Hori A, Honds S, Asada M, et al. Metastin suppresses the motility and growth of CHO cells transfected with its receptor [J]. Biochem Biophys Res Commun, 2001; 286(5): 958963.
23.	Becker JA, Mirjolet JF, Bernard J, et al. Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gqcoupled receptors [J]. Biochem Biophys Res Commun, 2005; 326(3): 677686.
24.	Yan C, Wang H, Boyd DD. KiSS1 represses 92kDa type Ⅳ collagenase expression by downregulating NFκB binding to the promoter as a consequence of IκB αinduced block of p65/p50 nuclear translocation [J]. J Biol Chem, 2001; 276(2): 11641172.
25.	Takino T, Koshikawa N, Miyamori H, et al. Cleavage of metastasis suppressor gene product KiSS1 protein/metastin by matrix metalloproteinases [J]. Oncogene, 2003; 22(30): 46174626.

1. 王雅辉, 叶晖, 王南鹏, 等. 抑癌基因TIP30在甲状腺乳头状癌中的表达与临床意义 [J]. 中国普外基础与临床杂志, 2009; 16(5): 356359.
2. Lee JH, Welch DR. Identification of highly expressed gene in metastasissuppressed chronmosome 6/human malignant melanoma hybrid cells using subtractive hybridization and differential display [J]. Int J Cancer, 1997; 71(6): 10351044.
3. Zhou Y, Damsky CH, Fisher SJ. Preeclampsia is associated with failure of human cytotrophoblasts to mimic a vascular adhesion phenotype. One cause of defective endovascular invasion in this syndrome? [J]. J Clin Invest, 1997; 99(9): 21522164.
4. 贺旭, 林建华. Kiss1与其受体GPR54在肿瘤转移中的作用 [J]. 中国医科大学学报, 2009; 8(4): 240244.
5. Poussin K, Dienes H, Sirma H, et al. Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas [J]. Int J Cancer, 1999; 80(4): 497505.
6. 胡淑阳, 吴艺捷. 甲状腺癌相关基因的研究进展 [J]. 医学综述, 2009; 15(13): 19531956.
7. 陈燕昌, 陈大良, 殷凤峙. 甲状腺癌组织中肿瘤转移抑制基因的异常表达及其临床意义 [J]. 中国普外基础与临床杂志, 1996; 3(3): 143145.
8. 姜军, 韩晓蓉. 甲状腺癌的分子生物学研究进展 [J]. 中国普外基础与临床杂志, 2000; 7(5): 326327.
9. Fidler IJ. Cancer bioligy: invasions and metastasis [A]. In: Abeloff MD, Armitage JO, Lichter AS, et al. Clinical Oncology [M]. 2nd eds. New York: Churchill Livingstone, 2000: 2953.
10. 孙治军, 姚榛祥. 表皮生长因子促进滤泡状和乳头状甲状腺癌增殖、转移和浸润的体内外试验 [J]. 中国普外基础与临床杂志, 1995; 2(3): 186, 157.
11. Lee JH, Welch DR. Suppression of metastasis in human breast carcinoma MDAMB435 cells after transfection with the metastasis suppressor gene, KiSS1 [J]. Cancer Res, 1997; 57(12): 23842387.
12. Welch DR, RinkerSchaeffer CW. What defines a useful marker of metastasis in human cancer? [J]. J Natl Cancer Inst, 1999; 91(16): 13511353.
13. Yoshida BA, Sokoloff MM, Welch DR, et al. Metastasissuppressor genes: a review and perspective on an emerging field [J]. J Natl Cancer Inst, 2000; 92(21): 17171730.
14. Lee JH, Miele ME, Hicks DJ, et al. KiSS1, a novel human malignant melanoma metastasissuppressor gene [J]. J Natl Cancer Inst, 1996; 88(23): 17311737.
15. Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS1 encodes peptide ligand of a Gproteincoupled receptor [J]. Nature, 2001; 411(6837): 613617.
16. Martin TA, Watkins G, Jiang WG. KiSS1 expression in human breast cancer [J]. Clin Exp Metastasis, 2005; 22(6): 503511.
17. SanchezCarbayo M, Capodieci P, CordonCardo C. Tumor suppressor role of KiSS1 in bladder cancer: loss of KiSS1 expression is associated with bladder cancer progression and clinical outcome [J]. Am J Pathol, 2003; 162(2): 609617.
18. Dhar DK, Naora H, Kubota H, et al. Downregulation of KiSS1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma [J]. Int J Cancer, 2004; 111(6): 868872.
19. Ikeguchi M, Hirooka Y, Kaibara N. Quantitative reverse transcriptase polymerase chain reaction analysis for KiSS1 and orphan Gproteincoupled receptor (hOT7T175) gene expression in hepatocellular carcinoma [J]. J Cancer Res Clin Oncol, 2003; 129(9): 531535.
20. Masui T, Doi R, Mori T, et al. Metastin and its variant forms suppress migration of pancreatic cancer cells [J]. Biochem Biophys Res Commun, 2004; 315(1): 8592.
21. Ikequchi M, Yamaquchi K, Kaibara N. Clinical significance of the loss of KiSS1 and orphan Gproteincoupled receptor (hOT7T175) gene expression in esophageal squamous cell carcinoma [J]. Clin Cancer Res, 2004; 10(4): 13791383.
22. Hori A, Honds S, Asada M, et al. Metastin suppresses the motility and growth of CHO cells transfected with its receptor [J]. Biochem Biophys Res Commun, 2001; 286(5): 958963.
23. Becker JA, Mirjolet JF, Bernard J, et al. Activation of GPR54 promotes cell cycle arrest and apoptosis of human tumor cells through a specific transcriptional program not shared by other Gqcoupled receptors [J]. Biochem Biophys Res Commun, 2005; 326(3): 677686.
24. Yan C, Wang H, Boyd DD. KiSS1 represses 92kDa type Ⅳ collagenase expression by downregulating NFκB binding to the promoter as a consequence of IκB αinduced block of p65/p50 nuclear translocation [J]. J Biol Chem, 2001; 276(2): 11641172.
25. Takino T, Koshikawa N, Miyamori H, et al. Cleavage of metastasis suppressor gene product KiSS1 protein/metastin by matrix metalloproteinases [J]. Oncogene, 2003; 22(30): 46174626.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and Clinical Significance of Tumor Suppressor Gene KiSS-1 in Papillary Thyroid Carcinoma

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