應用組織芯片技術檢測KiSS-1基因在膽囊癌中的表達_《中國普外基礎與臨床雜志》

作者：

呂志強 ¹ , 丁厚中 ² , 高泉根 ³ , 邱建平 ³ , 趙光明 ³ , 倪燦榮 ⁴ , 于觀貞 ⁵

1.江蘇大學臨床醫學院(江蘇鎮江212003);;
2.江蘇大學附屬昆山市第一人民醫院普外科(江蘇昆山215300);;
3.南通大學附屬吳江市第一人民醫院(江蘇吳江215200);;
4.第二軍醫大學長海醫院病理科(上海200433);;
5.第二軍醫大學長征醫院腫瘤科(上海200070）;

關鍵詞：

組織芯片 KiSS-1基因膽囊癌

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目的　探討轉移抑制基因KiSS-1在人膽囊癌轉移過程中的作用及臨床意義。
方法　應用組織芯片和免疫組織化學(EnVision)技術檢測KiSS-1在59例膽囊癌(其中肝臟侵犯13例,淋巴結轉移13例)、7例癌旁和6例正常膽囊組織中的表達。
結果　膽囊癌組織中KiSS-1的表達陽性率明顯低于正常和癌旁組織(P＜0.05)。在膽囊癌中,KiSS-1陽性表達與患者性別、年齡、腫瘤大小、組織學類型、分化程度及淋巴結轉移均無關,而與膽囊癌的浸潤深度、肝臟侵犯及臨床分期(Nevin分期)有關(P＜0.01)。KiSS-1在Ⅰ+Ⅱ期和Ⅲ+Ⅳ期以及Ⅴ期膽囊癌組織中的表達陽性率分別為92.3%、57.1%和27.8%,呈明顯下降趨勢(P=0.002)。
結論　KiSS-1的表達降低與人膽囊癌的發生及其侵襲、轉移過程密切相關,可能參與了膽囊癌的發生、侵襲及轉移過程的調控。

引用本文： 呂志強,丁厚中,高泉根,邱建平,趙光明,倪燦榮,于觀貞. 應用組織芯片技術檢測KiSS-1基因在膽囊癌中的表達. 中國普外基礎與臨床雜志, 2008, 15(9): 678-681. doi: 復制

1.	楊培, 嚴律南, 智星, 等. 122例原發性膽囊癌外科治療體會 [Ｊ]. 中國普外基礎與臨床雜志, 2004; 11(3)∶ 257.
2.	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.
3.	倪燦榮. 組織芯片的制備及在免疫組織化學中的應用 [Ｊ]. 第二軍醫大學學報, 2004; 25(10)∶ 1156.
4.	梁燕, 姜軍, 王清良, 等. 自制組織芯片研究VEGF-C在乳腺癌中的表達及其意義 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(5)∶ 580.
5.	Schraml P, Kononen J, Bubendorf L, et al. Tissue microarrays for gene amplification surveys in many different tumor types [Ｊ]. Clin Cancer Res, 1999; 5(8)∶ 1966.
6.	Brlund M, Forozan F, Kononen J, et al. Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarrays analysis [Ｊ]. J Natl Cancer Inst, 2000; 92(15)∶ 1252.
7.	Lee JH, Welch DR. Identification of highly expressed genes in metastasis-suppressed chromosome 6/human malignant melanoma hybrid cells using subtractive hybridization and differential display [Ｊ]. Int J Cancer, 1997; 71(6)∶ 1035.
8.	West A, Vojta P J, Welch DR, et al. Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1) [Ｊ]. Genomics, 1998; 54(1)∶ 145.
9.	Stark AM, Tongers K, Maass N, et al. Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases [Ｊ]. J Cancer Res Clin Oncol, 2005; 131(3)∶ 191.
10.	Martin TA, Watkins G, Jiang WG. KiSS-1 expression in human breast cancer [Ｊ]. Clin Exp Meta, 2005; 22(6)∶ 503.
11.	Mitchell DC, Abdelrahim M, Weng J, et al. Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2 alpha and specificity protein-1 [Ｊ]. J Biol Chem, 2006; 281(1)∶ 51.
12.	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.
13.	Ikeguchi M, Yamaguchi 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.
14.	Dhar DK, Naora H, Kubota H, et al. Downregulation of KiSS-1 expression is responsible for tumour invasion and worse prognosis in gastric carcinoma [Ｊ]. Int J Cancer， 2004; 111(6)∶ 868.
15.	Yu GZ, Chen Y, Ni CR, et al. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer [Ｊ]. Int J Exp Pathol, 2007; 88(3)∶ 175.
16.	Yu GZ , Wang JJ , Chen Y, et al. Significance of KiSS-1 and S100A4 in the process of metastasis of gastric carcinoma [Ｊ]. Chin-Germ J Clin Onco, 2006; 5(6)∶ 388.
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.
18.	Ringel MD, Hardy E, Bernet VJ, et al. Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells [Ｊ]. J Clin Endocrinol Metab, 2002; 87(5)∶ 2399.
19.	姜濤, 陸春雪, 張淑蘭, 等. 腫瘤轉移抑制基因KISS-1在子宮內膜癌組織中的表達及意義 [Ｊ]. 中國現代醫學雜志, 2006; 16(13)∶ 1933.
20.	孟麗榮, 張淑蘭, 魯艷明, 等. KiSS-1基因的表達對裸鼠子宮內膜癌皮下種植瘤的影響 [Ｊ]. 中華腫瘤防治雜志, 2006; 13(23)∶ 1785.
21.	Jiang Y, Berk M, Singh LS, et al. KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha [Ｊ]. Clin Exp Metastasis, 2005; 22(5)∶ 369.

1. 　楊培, 嚴律南, 智星, 等. 122例原發性膽囊癌外科治療體會 [Ｊ]. 中國普外基礎與臨床雜志, 2004; 11(3)∶ 257.
2. 　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.
3. 　倪燦榮. 組織芯片的制備及在免疫組織化學中的應用 [Ｊ]. 第二軍醫大學學報, 2004; 25(10)∶ 1156.
4. 　梁燕, 姜軍, 王清良, 等. 自制組織芯片研究VEGF-C在乳腺癌中的表達及其意義 [Ｊ]. 中國普外基礎與臨床雜志, 2006; 13(5)∶ 580.
5. 　Schraml P, Kononen J, Bubendorf L, et al. Tissue microarrays for gene amplification surveys in many different tumor types [Ｊ]. Clin Cancer Res, 1999; 5(8)∶ 1966.
6. 　Brlund M, Forozan F, Kononen J, et al. Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarrays analysis [Ｊ]. J Natl Cancer Inst, 2000; 92(15)∶ 1252.
7. 　Lee JH, Welch DR. Identification of highly expressed genes in metastasis-suppressed chromosome 6/human malignant melanoma hybrid cells using subtractive hybridization and differential display [Ｊ]. Int J Cancer, 1997; 71(6)∶ 1035.
8. 　West A, Vojta P J, Welch DR, et al. Chromosome localization and genomic structure of the KiSS-1 metastasis suppressor gene (KISS1) [Ｊ]. Genomics, 1998; 54(1)∶ 145.
9. 　Stark AM, Tongers K, Maass N, et al. Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases [Ｊ]. J Cancer Res Clin Oncol, 2005; 131(3)∶ 191.
10. 　Martin TA, Watkins G, Jiang WG. KiSS-1 expression in human breast cancer [Ｊ]. Clin Exp Meta, 2005; 22(6)∶ 503.
11. 　Mitchell DC, Abdelrahim M, Weng J, et al. Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2 alpha and specificity protein-1 [Ｊ]. J Biol Chem, 2006; 281(1)∶ 51.
12. 　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.
13. 　Ikeguchi M, Yamaguchi 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.
14. 　Dhar DK, Naora H, Kubota H, et al. Downregulation of KiSS-1 expression is responsible for tumour invasion and worse prognosis in gastric carcinoma [Ｊ]. Int J Cancer， 2004; 111(6)∶ 868.
15. 　Yu GZ, Chen Y, Ni CR, et al. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer [Ｊ]. Int J Exp Pathol, 2007; 88(3)∶ 175.
16. 　Yu GZ , Wang JJ , Chen Y, et al. Significance of KiSS-1 and S100A4 in the process of metastasis of gastric carcinoma [Ｊ]. Chin-Germ J Clin Onco, 2006; 5(6)∶ 388.
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.
18. 　Ringel MD, Hardy E, Bernet VJ, et al. Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells [Ｊ]. J Clin Endocrinol Metab, 2002; 87(5)∶ 2399.
19. 　姜濤, 陸春雪, 張淑蘭, 等. 腫瘤轉移抑制基因KISS-1在子宮內膜癌組織中的表達及意義 [Ｊ]. 中國現代醫學雜志, 2006; 16(13)∶ 1933.
20. 　孟麗榮, 張淑蘭, 魯艷明, 等. KiSS-1基因的表達對裸鼠子宮內膜癌皮下種植瘤的影響 [Ｊ]. 中華腫瘤防治雜志, 2006; 13(23)∶ 1785.
21. 　Jiang Y, Berk M, Singh LS, et al. KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha [Ｊ]. Clin Exp Metastasis, 2005; 22(5)∶ 369.

《中國普外基礎與臨床雜志》

應用組織芯片技術檢測KiSS-1基因在膽囊癌中的表達

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《中國普外基礎與臨床雜志》

應用組織芯片技術檢測KiSS-1基因在膽囊癌中的表達

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