• 貴陽醫(yī)學(xué)院附屬醫(yī)院甲狀腺外科（貴陽550004）;

目的 通過檢測(cè)KiSS-1蛋白在甲狀腺乳頭狀癌中的表達(dá)情況，探討其在甲狀腺乳頭狀癌中的表達(dá)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(biāo)本，采用免疫組化檢測(cè)KiSS-1蛋白的表達(dá)，并分析其與甲狀腺乳頭狀癌臨床病理特征的關(guān)系。
結(jié)果 KiSS-1蛋白主要表達(dá)于細(xì)胞膜與細(xì)胞質(zhì)中。32例患者癌旁組織中KiSS-1蛋白表達(dá)均為陽性（100%），在癌組織中表達(dá)減少或缺失，11例（34.4%）表達(dá)陽性，21例（65.6%）表達(dá)陰性，其差異有統(tǒng)計(jì)學(xué)意義（χ2=31.256，P lt;0.001）。KiSS-1蛋白在癌組織中表達(dá)的平均A值為119.595 2，在癌旁組織中為174.805 0，差異有統(tǒng)計(jì)學(xué)意義（t=34.429,P lt;0.001）。癌組織中KiSS1蛋白的表達(dá)與患者性別（P=0.618）及年齡（P=0.061）均無關(guān)，而與腫瘤TNM分期有關(guān)（P=0.034）。KiSS-1蛋白在有淋巴結(jié)轉(zhuǎn)移的癌組織中和無淋巴結(jié)轉(zhuǎn)移的癌組織中的表達(dá)陽性率分別為100%（4/4）和25.0%（7/28），差異有統(tǒng)計(jì)學(xué)意義（P=0.003）。
結(jié)論 KiSS-1蛋白在甲狀腺乳頭狀癌中表達(dá)減少或缺失，可能參與腫瘤的發(fā)生、侵襲和轉(zhuǎn)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(dá)及其臨床意義. 中國(guó)普外基礎(chǔ)與臨床雜志, 2010, 17(8): 775-779. doi: 復(fù)制

版權(quán)信息： ?四川大學(xué)華西醫(yī)院華西期刊社《中國(guó)普外基礎(chǔ)與臨床雜志》版權(quán)所有，未經(jīng)授權(quán)不得轉(zhuǎn)載、改編

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(dá)與臨床意義 [J]. 中國(guó)普外基礎(chǔ)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(zhuǎn)移中的作用 [J]. 中國(guó)醫(yī)科大學(xué)學(xué)報(bào), 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(guān)基因的研究進(jìn)展 [J]. 醫(yī)學(xué)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(zhuǎn)移抑制基因的異常表達(dá)及其臨床意義 [J]. 中國(guó)普外基礎(chǔ)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(xué)研究進(jìn)展 [J]. 中國(guó)普外基礎(chǔ)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(zhǎng)因子促進(jìn)濾泡狀和乳頭狀甲狀腺癌增殖、轉(zhuǎn)移和浸潤(rùn)的體內(nèi)外試驗(yàn) [J]. 中國(guó)普外基礎(chǔ)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. 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(dá)與臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009; 16(5): 356359.
  2. 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. 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. 4. 賀旭, 林建華. Kiss1與其受體GPR54在腫瘤轉(zhuǎn)移中的作用 [J]. 中國(guó)醫(yī)科大學(xué)學(xué)報(bào), 2009; 8(4): 240244.
  5. 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. 6. 胡淑陽, 吳藝捷. 甲狀腺癌相關(guān)基因的研究進(jìn)展 [J]. 醫(yī)學(xué)綜述, 2009; 15(13): 19531956.
  7. 7. 陳燕昌, 陳大良, 殷鳳峙. 甲狀腺癌組織中腫瘤轉(zhuǎn)移抑制基因的異常表達(dá)及其臨床意義 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 1996; 3(3): 143145.
  8. 8. 姜軍, 韓曉蓉. 甲狀腺癌的分子生物學(xué)研究進(jìn)展 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2000; 7(5): 326327.
  9. 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. 10. 孫治軍, 姚榛祥. 表皮生長(zhǎng)因子促進(jìn)濾泡狀和乳頭狀甲狀腺癌增殖、轉(zhuǎn)移和浸潤(rùn)的體內(nèi)外試驗(yàn) [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 1995; 2(3): 186, 157.
  11. 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. 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. 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. 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. 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. 16. Martin TA, Watkins G, Jiang WG. KiSS1 expression in human breast cancer [J]. Clin Exp Metastasis, 2005; 22(6): 503511.
  17. 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. 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. 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. 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. 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. 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. 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. 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. 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.