胃腺癌中CBX8的表达与临床病理特征及预后的关系
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摘要
目的探讨CBX8在胃腺癌组织中的表达及其临床意义。方法收集119例原发性胃腺癌手术切除标本及癌旁正常组织,应用组织芯片、免疫组化PV 6000法检测胃腺癌组织、癌旁正常组织中CBX8的表达,并分析其表达与胃腺癌临床病理特征及生存预后的关系。结果 CBX8在胃腺癌、癌旁正常组织高表达率分别为46. 2%(55/119)、13. 4%(16/119),两者差异有统计学意义(χ2=30. 53,P <0. 01)。胃腺癌组织中CBX8表达与分化程度、临床分期及有无淋巴结转移相关(P <0. 05)。CBX8在低分化胃腺癌组中的高表达率低于中、高分化胃腺癌组,Ⅰ+Ⅱ期胃腺癌中CBX8的高表达率高于Ⅲ+Ⅳ期; CBX8高表达的胃腺癌患者转移率低。Cox回归分析表明,CBX8表达、临床分期、淋巴结转移是影响胃腺癌患者术后总生存期和无瘤生存期的独立预后因素(P <0. 05)。Kaplan-Meier分析显示,CBX8高表达的胃腺癌患者术后总生存期(P=0. 004)和无瘤生存期(P=0. 004)比低表达的患者长。结论 CBX8可能参与胃腺癌的发生、发展过程,是影响患者预后的独立因素之一,检测其表达对评价胃腺癌可能具有重要的临床价值,并有望成为胃腺癌靶向治疗的新靶点。
Purpose To explore the expression of CBX8 in gastric adenocarcinoma tissue and its clinical significance.Methods 119 cases of primary gastric adenocarcinoma treated by surgery and corresponding adjacent normal tissues were collected. The protein expression levels of CBX8 in gastric adenocarcinoma and their corresponding adjacent normal tissue was determined using tissue microarray and immunohistochemistry PV 6000 method staining. The relationship between CBX8 expression and clinicopathologic characters and survival prognosis was analyzed. Results The positive expression rate of CBX8 in gastric cancer and their corresponding adjacent normal tissue was46. 2%( 55/119) and 13. 4%( 16/119) respectively. There was statistically significant difference between two groups( χ2=30. 53,P < 0. 01). The expression of CBX8 in gastric adenocarcinoma tissue was obviously correlated with the differentiation,clinical staging,and lymph node metastasis( P < 0. 05). The high expression rate of CBX8 in the poorly differentiated gastric adenocarcinoma was lower than moderately differentiated and well differentiated group. The high expression rate of CBX8 in stage Ⅰ + Ⅱ gastric adenocarcinoma was higher than that in stage Ⅲ + Ⅳ. The gastric adenocarcinoma patients with high expression of CBX8 had low metastasis rate. Cox multivariate analysis showed CBX8,clinical staging,and lymphatic metastasis were independent predictors of overall survival and disease-free survival( P < 0. 05). Kaplan-Meier analysis showed that the patients with higher expression of CBX8 had both longer overall survival time( P = 0. 004) and disease-free survival time( P =0. 004). Conclusion The expression of CBX8 may be involved in the tumorigenesis and progression of gastric adenocarcinoma.CBX8 is one of the independent predictor of prognosis,and the detecting of CBX8 expression may have important clinical value for the evaluation of gastric adenocarcinoma. CBX8 may became a new target for target therapy of gastric adenocarcinoma.
Purpose To explore the expression of CBX8 in gastric adenocarcinoma tissue and its clinical significance.Methods 119 cases of primary gastric adenocarcinoma treated by surgery and corresponding adjacent normal tissues were collected. The protein expression levels of CBX8 in gastric adenocarcinoma and their corresponding adjacent normal tissue was determined using tissue microarray and immunohistochemistry PV 6000 method staining. The relationship between CBX8 expression and clinicopathologic characters and survival prognosis was analyzed. Results The positive expression rate of CBX8 in gastric cancer and their corresponding adjacent normal tissue was46. 2%( 55/119) and 13. 4%( 16/119) respectively. There was statistically significant difference between two groups( χ2=30. 53,P < 0. 01). The expression of CBX8 in gastric adenocarcinoma tissue was obviously correlated with the differentiation,clinical staging,and lymph node metastasis( P < 0. 05). The high expression rate of CBX8 in the poorly differentiated gastric adenocarcinoma was lower than moderately differentiated and well differentiated group. The high expression rate of CBX8 in stage Ⅰ + Ⅱ gastric adenocarcinoma was higher than that in stage Ⅲ + Ⅳ. The gastric adenocarcinoma patients with high expression of CBX8 had low metastasis rate. Cox multivariate analysis showed CBX8,clinical staging,and lymphatic metastasis were independent predictors of overall survival and disease-free survival( P < 0. 05). Kaplan-Meier analysis showed that the patients with higher expression of CBX8 had both longer overall survival time( P = 0. 004) and disease-free survival time( P =0. 004). Conclusion The expression of CBX8 may be involved in the tumorigenesis and progression of gastric adenocarcinoma.CBX8 is one of the independent predictor of prognosis,and the detecting of CBX8 expression may have important clinical value for the evaluation of gastric adenocarcinoma. CBX8 may became a new target for target therapy of gastric adenocarcinoma.
引文
[1]刘家园,常家聪,刘弋,王道兵.胃癌组织中Cdc42、β1整合素的表达及临床意义[J].临床与实验病理学杂志,2014,30(6):618-621.
[2]Kerppola T K.Polycomb group complexes---many combinations,many functions[J].Trends Cell Biol,2009,19(12):692-704.
[3]Zhou X,Zhang H L,Gu G F,et al.Investigation of the relationship between chromobox homolog 8 and nucleus pulposus cells degeneration in rat interverteral disc[J].In Vitro Cell Dev Biol Anim,2013,49(4):279-286.
[4]Ma R G,Zhang Y,Sun T T,Cheng B.Epigenetic regulation by polycomb group complexes:focus on roles of CBX8 proteins[J].JZhejiang Univ Sci B,2014,15(5):412-428.
[5]Simon J A,Kingston R E.Mechanisms of polycomb gene silencing:knowns and unknowns[J].Nat Rev Mol Cell Biol,2009,10(10):697-708.
[6]Sauvageau M,Sauvageau G.Polycomb group proteins:multi-faceted regulators of somatic stem cells and cancer[J].Cell Stem Cell,2010,7(3):299-313.
[7]Luis N M,Morey L,Mejetta S,et al.Regulation of human epidermal stem cell proliferation and senescence requires polycombdependent and-independent functions of Cbx4[J].Cell Stem Cell,2011,9(3):233-246.
[8]姚响芸,王萌,薛丽香.Polycomb蛋白复合体对细胞衰老的表观遗传学调控[J].中国分子化学与生物学报,2012,28(4):304-309.
[9]Maertens G N,El Messaoudi-Aubert S,Racek T,et al.Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus[J].PLo S One,2009,4(7):e6380.
[10]Xiao W,Ou C,Qin J,et al.CBX8,a novel DNA repair protein,promotes tumorigenesis in human esophageal carcinoma[J].Int JClin Exp Pathol,2014,7(8):4817-4826.
[11]Gao S B,Sun S L,Zheng Q L,et al.Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma[J].Am J Cancer Res,2015,5(10):2969-2979.
[12]Tang J,Wang G,Zhang M,et al.Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer[J].Oncotarget,2014,5(21):10778-10790.
[13]Wang G,Tang J,Zhan W,et al.CBX8 suppresses tumor metastasis via repressing snail in esophageal squamous cell carcinoma[J].Theranostics,2017,7(14):3478-3488.
[2]Kerppola T K.Polycomb group complexes---many combinations,many functions[J].Trends Cell Biol,2009,19(12):692-704.
[3]Zhou X,Zhang H L,Gu G F,et al.Investigation of the relationship between chromobox homolog 8 and nucleus pulposus cells degeneration in rat interverteral disc[J].In Vitro Cell Dev Biol Anim,2013,49(4):279-286.
[4]Ma R G,Zhang Y,Sun T T,Cheng B.Epigenetic regulation by polycomb group complexes:focus on roles of CBX8 proteins[J].JZhejiang Univ Sci B,2014,15(5):412-428.
[5]Simon J A,Kingston R E.Mechanisms of polycomb gene silencing:knowns and unknowns[J].Nat Rev Mol Cell Biol,2009,10(10):697-708.
[6]Sauvageau M,Sauvageau G.Polycomb group proteins:multi-faceted regulators of somatic stem cells and cancer[J].Cell Stem Cell,2010,7(3):299-313.
[7]Luis N M,Morey L,Mejetta S,et al.Regulation of human epidermal stem cell proliferation and senescence requires polycombdependent and-independent functions of Cbx4[J].Cell Stem Cell,2011,9(3):233-246.
[8]姚响芸,王萌,薛丽香.Polycomb蛋白复合体对细胞衰老的表观遗传学调控[J].中国分子化学与生物学报,2012,28(4):304-309.
[9]Maertens G N,El Messaoudi-Aubert S,Racek T,et al.Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus[J].PLo S One,2009,4(7):e6380.
[10]Xiao W,Ou C,Qin J,et al.CBX8,a novel DNA repair protein,promotes tumorigenesis in human esophageal carcinoma[J].Int JClin Exp Pathol,2014,7(8):4817-4826.
[11]Gao S B,Sun S L,Zheng Q L,et al.Genetic alteration and misexpression of Polycomb group genes in hepatocellular carcinoma[J].Am J Cancer Res,2015,5(10):2969-2979.
[12]Tang J,Wang G,Zhang M,et al.Paradoxical role of CBX8 in proliferation and metastasis of colorectal cancer[J].Oncotarget,2014,5(21):10778-10790.
[13]Wang G,Tang J,Zhan W,et al.CBX8 suppresses tumor metastasis via repressing snail in esophageal squamous cell carcinoma[J].Theranostics,2017,7(14):3478-3488.