• 貴陽醫(yī)學(xué)院附屬醫(yī)院肛腸外科(貴州貴陽 550004);

目的  探討結(jié)直腸癌遠(yuǎn)處轉(zhuǎn)移患者免疫基因表達(dá)的變化趨勢(shì)。
方法  從16例結(jié)直腸癌患者的原發(fā)癌腫瘤組織中提取mRNA,采用基因芯片技術(shù)檢測(cè)8例有肝臟轉(zhuǎn)移和無肝臟轉(zhuǎn)移的結(jié)直腸癌患者的免疫基因表達(dá)。
結(jié)果  與無肝臟轉(zhuǎn)移的結(jié)直腸癌患者相比,有肝臟轉(zhuǎn)移的結(jié)直腸癌患者的腫瘤組織中有11條免疫基因即羧基肽酶D、高親和力IgE Fc受體γ鏈、低親和力IgG FcⅢa受體、游離脂肪酸受體2、白細(xì)胞介素-2γ鏈、受體型蛋白酪氨酸磷酸酶C、補(bǔ)體B因子、人類白細(xì)胞抗原復(fù)合物(HLA)-DMA、HLA-DMB、HLA-DQA1和顆粒酶B均表達(dá)下調(diào)。涉及功能變化包括免疫細(xì)胞的生長(zhǎng)激活、信號(hào)傳遞、腫瘤免疫原性、細(xì)胞因子、受體、補(bǔ)體、腫瘤細(xì)胞凋亡等方面。
結(jié)論  在結(jié)直腸癌肝轉(zhuǎn)移患者中免疫基因的表達(dá)普遍下調(diào),從多種途徑影響機(jī)體免疫功能的發(fā)揮,使癌細(xì)胞逃避機(jī)體免疫系統(tǒng)殺滅而在遠(yuǎn)處目標(biāo)臟器生長(zhǎng)、繁殖。

引用本文: 顏登國,王國棟,程海玉. 基因芯片技術(shù)分析結(jié)直腸癌肝轉(zhuǎn)移患者免疫基因表達(dá)的變化△. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(11): 1182-1186. doi: 復(fù)制

1. 孫立峰, 丁凌, 范鈺, 等. 結(jié)直腸腫瘤肝轉(zhuǎn)移基礎(chǔ)研究概況[J]. 實(shí)用腫瘤雜志, 2007, 22(3):198-200.
2. 屈伸, 劉志國. 分子生物學(xué)實(shí)驗(yàn)技術(shù)[M]. 北京:化學(xué)工業(yè)出版社, 2007:364-398.
3. 邢戌健, 賈戶亮, 張磊, 等. 基因芯片技術(shù)在肝細(xì)胞癌候選診斷指標(biāo)篩選中的應(yīng)用[J]. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(1):23-27.
4. 張紅, 楚勝華, 馮東福, 等. 應(yīng)用基因芯片篩選不同膠質(zhì)瘤細(xì)胞相關(guān)基因[J]. 中華實(shí)驗(yàn)外科雜志, 2012, 29(2):253-255.
5. Boltze C. Loss of maspin is a helpful prognosticator in colorectal cancer:a tissue microarray analysis[J]. Pathol Res Pract, 2005, 200(11-12):783-790.
6. 文坤明, 曾慶良, 馮國麗, 等. 結(jié)直腸癌患者淋巴結(jié)微轉(zhuǎn)移與其免疫功能的關(guān)系[J]. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(11):890-894.
7. Ge W, Hu H, Zheng S. High osteopontin and low SPARC-like 1 co-expression in colorectal liver metastasis were identified by integrated analysis of cytoband and microarray[C]. American Association for Cancer Research Annual Meeting:Proceedings. 2007 Apr 14-18;Los Angeles, CA. Philadelphia (PA):AACR;2007. Abstract nr 4701.
8. 丁友成, 張輝, 鐘明安, 等. 基因芯片技術(shù)篩選大腸癌肝轉(zhuǎn)移差異表達(dá)基因[J]. 南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版), 2008, 28(4):476-479.
9. Le GT, Abbenante G, Fairlie DP. Profiling the enzymatic properties and inhibition of human complement factor B[J]. J Biol Chem, 2007, 282(48):34809-34816.
10. Yio XY, Mayer L. Characterization of a 180-kDa intestinalepithelial cell membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial cell interactions[J]. J Biol Chem, 1997, 272(19):12786-12792.
11. 孫仁山, 陳曉紅, 冉新澤, 等. 高親和力IgE受體介導(dǎo)的信號(hào)傳導(dǎo)及其相關(guān)的抑制性受體[J]. 中國藥理學(xué)通報(bào), 2005, 21(4):385-389.
12. Wu J, Edberg JC, Redecha PB, et al. A novel polymorphism of Fc gamma RⅢa (CD16) alters receptor function and predisposes to autoimmune disease[J]. J Clin Invest, 1997, 100(5):1059-1070.
13. Zhang W, Gordon M, Schultheis AM, et al. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab[J]. J Clin Oncol, 2007, 25(24):3712-3718.
14. Senga T, Iwamoto S, Yoshida T, et al. LSSIG is a novel murineleukocyte-specific GPCR that is induced by the activation of STAT3[J]. Blood, 2003, 101(3):1185-1187.
15. Nilsson NE, Kotarsky K, Owman C, et al. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids[J]. Biochem Biophys Res Commun, 2003, 303(4):1047-1052.
16. Karaki S, Tazoe H, Hayashi H, et al. Expression of the short-chain fatty acid receptor, GPR43, in the human colon[J]. J Mol Histol, 2008, 39(2):135-142.
17. Tang Y, Chen Y, Jiang H, et al. G-protein-coupled receptor for short-chain fatty acids suppresses colon Cancer[J]. Int J Cancer,.
18. Pashine A, Busch R, Belmares MP, et al. Interaction of HLA-DRwith an acidic face of HLA-DM disrupts sequence-dependentinteractions with peptides[J]. Immunity, 2003, 19(2):183-192.
19. Brocke P, Garbi N, Momburg F, et al. HLA-DM, HLA-DO and tapasin:functional similarities and differences[J]. Curr Opin Immunol, 2002, 14(1):22-29.
20. Callahan MJ, Nagymanyoki Z, Bonome T, et al. Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer[J]. Clin Cancer Res, 2008, 14(23):7667-7673.
21. Seung S, Urban JL, Schreiber H. A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+T cells to an antigen that no longer serves as a target[J]. J Exp Med, 1993, 178(3):933-940.
22. Arboleda MJ, Lyons JF, Kabbinavar FF, et al. Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1integrins, increased invasion, and metastasis of human breast and ovarian cancer cells[J]. Cancer Res, 2003, 63(1):196-206.
23. Zhu JW, Brdicka T, Katsumoto TR, et al. Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling[J]. Immunity, 2008, 28(2):183-196.
24. Penninger JM, Irie-Sasaki J, Sasaki T, et al. CD45:new jobs for an old acquaintance[J]. Nat Immunol, 2001, 2(5):389-396.
25. , 128(4):847-856.
  1. 1. 孫立峰, 丁凌, 范鈺, 等. 結(jié)直腸腫瘤肝轉(zhuǎn)移基礎(chǔ)研究概況[J]. 實(shí)用腫瘤雜志, 2007, 22(3):198-200.
  2. 2. 屈伸, 劉志國. 分子生物學(xué)實(shí)驗(yàn)技術(shù)[M]. 北京:化學(xué)工業(yè)出版社, 2007:364-398.
  3. 3. 邢戌健, 賈戶亮, 張磊, 等. 基因芯片技術(shù)在肝細(xì)胞癌候選診斷指標(biāo)篩選中的應(yīng)用[J]. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(1):23-27.
  4. 4. 張紅, 楚勝華, 馮東福, 等. 應(yīng)用基因芯片篩選不同膠質(zhì)瘤細(xì)胞相關(guān)基因[J]. 中華實(shí)驗(yàn)外科雜志, 2012, 29(2):253-255.
  5. 5. Boltze C. Loss of maspin is a helpful prognosticator in colorectal cancer:a tissue microarray analysis[J]. Pathol Res Pract, 2005, 200(11-12):783-790.
  6. 6. 文坤明, 曾慶良, 馮國麗, 等. 結(jié)直腸癌患者淋巴結(jié)微轉(zhuǎn)移與其免疫功能的關(guān)系[J]. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(11):890-894.
  7. 7. Ge W, Hu H, Zheng S. High osteopontin and low SPARC-like 1 co-expression in colorectal liver metastasis were identified by integrated analysis of cytoband and microarray[C]. American Association for Cancer Research Annual Meeting:Proceedings. 2007 Apr 14-18;Los Angeles, CA. Philadelphia (PA):AACR;2007. Abstract nr 4701.
  8. 8. 丁友成, 張輝, 鐘明安, 等. 基因芯片技術(shù)篩選大腸癌肝轉(zhuǎn)移差異表達(dá)基因[J]. 南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版), 2008, 28(4):476-479.
  9. 9. Le GT, Abbenante G, Fairlie DP. Profiling the enzymatic properties and inhibition of human complement factor B[J]. J Biol Chem, 2007, 282(48):34809-34816.
  10. 10. Yio XY, Mayer L. Characterization of a 180-kDa intestinalepithelial cell membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial cell interactions[J]. J Biol Chem, 1997, 272(19):12786-12792.
  11. 11. 孫仁山, 陳曉紅, 冉新澤, 等. 高親和力IgE受體介導(dǎo)的信號(hào)傳導(dǎo)及其相關(guān)的抑制性受體[J]. 中國藥理學(xué)通報(bào), 2005, 21(4):385-389.
  12. 12. Wu J, Edberg JC, Redecha PB, et al. A novel polymorphism of Fc gamma RⅢa (CD16) alters receptor function and predisposes to autoimmune disease[J]. J Clin Invest, 1997, 100(5):1059-1070.
  13. 13. Zhang W, Gordon M, Schultheis AM, et al. FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab[J]. J Clin Oncol, 2007, 25(24):3712-3718.
  14. 14. Senga T, Iwamoto S, Yoshida T, et al. LSSIG is a novel murineleukocyte-specific GPCR that is induced by the activation of STAT3[J]. Blood, 2003, 101(3):1185-1187.
  15. 15. Nilsson NE, Kotarsky K, Owman C, et al. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids[J]. Biochem Biophys Res Commun, 2003, 303(4):1047-1052.
  16. 16. Karaki S, Tazoe H, Hayashi H, et al. Expression of the short-chain fatty acid receptor, GPR43, in the human colon[J]. J Mol Histol, 2008, 39(2):135-142.
  17. 17. Tang Y, Chen Y, Jiang H, et al. G-protein-coupled receptor for short-chain fatty acids suppresses colon Cancer[J]. Int J Cancer,.
  18. 18. Pashine A, Busch R, Belmares MP, et al. Interaction of HLA-DRwith an acidic face of HLA-DM disrupts sequence-dependentinteractions with peptides[J]. Immunity, 2003, 19(2):183-192.
  19. 19. Brocke P, Garbi N, Momburg F, et al. HLA-DM, HLA-DO and tapasin:functional similarities and differences[J]. Curr Opin Immunol, 2002, 14(1):22-29.
  20. 20. Callahan MJ, Nagymanyoki Z, Bonome T, et al. Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer[J]. Clin Cancer Res, 2008, 14(23):7667-7673.
  21. 21. Seung S, Urban JL, Schreiber H. A tumor escape variant that has lost one major histocompatibility complex class I restriction element induces specific CD8+T cells to an antigen that no longer serves as a target[J]. J Exp Med, 1993, 178(3):933-940.
  22. 22. Arboleda MJ, Lyons JF, Kabbinavar FF, et al. Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1integrins, increased invasion, and metastasis of human breast and ovarian cancer cells[J]. Cancer Res, 2003, 63(1):196-206.
  23. 23. Zhu JW, Brdicka T, Katsumoto TR, et al. Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling[J]. Immunity, 2008, 28(2):183-196.
  24. 24. Penninger JM, Irie-Sasaki J, Sasaki T, et al. CD45:new jobs for an old acquaintance[J]. Nat Immunol, 2001, 2(5):389-396.
  25. 25. , 128(4):847-856.