KiSS-1在甲狀腺乳頭狀癌中的表達及其臨床意義_《中國普外基礎與臨床雜志》

作者：

高榮君 , 王南鵬 , 葉暉 , 高慶軍 , 周彥 , 段海松 , 趙代偉

貴陽醫學院附屬醫院甲狀腺外科（貴陽550004）;

關鍵詞：

甲狀腺乳頭狀癌 KiSS-1蛋白轉移抑素侵襲轉移免疫組織化學

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目的通過檢測KiSS-1蛋白在甲狀腺乳頭狀癌中的表達情況，探討其在甲狀腺乳頭狀癌中的表達及其意義。
方法選取32例臨床確診的甲狀腺乳頭狀癌患者癌組織及其癌旁組織病理蠟塊標本，采用免疫組化檢測KiSS-1蛋白的表達，并分析其與甲狀腺乳頭狀癌臨床病理特征的關系。
結果 KiSS-1蛋白主要表達于細胞膜與細胞質中。32例患者癌旁組織中KiSS-1蛋白表達均為陽性（100%），在癌組織中表達減少或缺失，11例（34.4%）表達陽性，21例（65.6%）表達陰性，其差異有統計學意義（χ2=31.256，P lt;0.001）。KiSS-1蛋白在癌組織中表達的平均A值為119.595 2，在癌旁組織中為174.805 0，差異有統計學意義（t=34.429,P lt;0.001）。癌組織中KiSS1蛋白的表達與患者性別（P=0.618）及年齡（P=0.061）均無關，而與腫瘤TNM分期有關（P=0.034）。KiSS-1蛋白在有淋巴結轉移的癌組織中和無淋巴結轉移的癌組織中的表達陽性率分別為100%（4/4）和25.0%（7/28），差異有統計學意義（P=0.003）。
結論 KiSS-1蛋白在甲狀腺乳頭狀癌中表達減少或缺失，可能參與腫瘤的發生、侵襲和轉移。

引用本文： 高榮君,王南鵬,葉暉,高慶軍,周彥,段海松,趙代偉. KiSS-1在甲狀腺乳頭狀癌中的表達及其臨床意義. 中國普外基礎與臨床雜志, 2010, 17(8): 775-779. doi: 復制

1.	王雅輝, 葉暉, 王南鵬, 等. 抑癌基因TIP30在甲狀腺乳頭狀癌中的表達與臨床意義 [J]. 中國普外基礎與臨床雜志, 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.	賀旭, 林建華. Kiss1與其受體GPR54在腫瘤轉移中的作用 [J]. 中國醫科大學學報, 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.	胡淑陽, 吳藝捷. 甲狀腺癌相關基因的研究進展 [J]. 醫學綜述, 2009; 15(13): 19531956.
7.	陳燕昌, 陳大良, 殷鳳峙. 甲狀腺癌組織中腫瘤轉移抑制基因的異常表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 1996; 3(3): 143145.
8.	姜軍, 韓曉蓉. 甲狀腺癌的分子生物學研究進展 [J]. 中國普外基礎與臨床雜志, 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.	孫治軍, 姚榛祥. 表皮生長因子促進濾泡狀和乳頭狀甲狀腺癌增殖、轉移和浸潤的體內外試驗 [J]. 中國普外基礎與臨床雜志, 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. 王雅輝, 葉暉, 王南鵬, 等. 抑癌基因TIP30在甲狀腺乳頭狀癌中的表達與臨床意義 [J]. 中國普外基礎與臨床雜志, 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. 賀旭, 林建華. Kiss1與其受體GPR54在腫瘤轉移中的作用 [J]. 中國醫科大學學報, 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. 胡淑陽, 吳藝捷. 甲狀腺癌相關基因的研究進展 [J]. 醫學綜述, 2009; 15(13): 19531956.
7. 陳燕昌, 陳大良, 殷鳳峙. 甲狀腺癌組織中腫瘤轉移抑制基因的異常表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 1996; 3(3): 143145.
8. 姜軍, 韓曉蓉. 甲狀腺癌的分子生物學研究進展 [J]. 中國普外基礎與臨床雜志, 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. 孫治軍, 姚榛祥. 表皮生長因子促進濾泡狀和乳頭狀甲狀腺癌增殖、轉移和浸潤的體內外試驗 [J]. 中國普外基礎與臨床雜志, 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.

《中國普外基礎與臨床雜志》

KiSS-1在甲狀腺乳頭狀癌中的表達及其臨床意義

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《中國普外基礎與臨床雜志》

KiSS-1在甲狀腺乳頭狀癌中的表達及其臨床意義

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