细胞周期蛋白D1、CD44表达与可切除胃腺癌临床病理特征的相关性
|
摘要
目的探讨细胞周期蛋白D1(Cyclin D1)和CD44的不同表达状态与可切除胃腺癌根治术后患者临床病理学特征的关系。方法选取104例可切除胃腺癌根治术后患者,用免疫组化方法研究其病理蜡块切片中胃腺癌组织中Cyclin D1和CD44的表达状况,对Cyclin D1、CD44的表达状态与患者临床及病理资料结果进行统计学分析。结果在胃腺癌组织中Cyclin D1、CD44均有较高的高表达率(高表达率分别为40. 4%、53. 8%)。Cyclin D1和CD44的高低表达组在年龄、性别、肿瘤位置、淋巴结清扫范围等临床病理参数的构成比方面无显著差异(P> 0. 05),在术前血清乳酸脱氢酶(LDH)、T分期、N分期、Lauren分型、组织学分级等临床病理参数的构成比方面有显著差异(P <0. 05)。相关性分析提示,Cyclin D1、CD44的各自表达状态与术前血清乳酸脱氢酶、T分期、N分期、组织学分级、Lauren分型有统计学意义的低度正相关性(r值0. 2～0. 4)。Cyclin D1和CD44的表达状态呈现高度正相关(r=0. 736)。结论 Cyclin D1和CD44在胃腺癌癌组织中有较高的高表达率。Cyclin D1和CD44的表达状态与胃腺癌术前血清乳酸脱氢酶、术后T分期、N分期、Lauren分型、组织学分级等临床病理学特征有关联,但是均为弱相关。Cyclin D1和CD44表达状态强相关。
Objective To explore the correlation between expression of Cyclin D1,CD44 and clinicopathological characteristics of patients with radical resection of gastric adenocarcinoma.Methods A total of 104 patients with gastric adenocarcinoma after radical resection were selected,the expressions of Cyclin D1,CD44 in gastric adenocarcinoma tissues in the pathological wax block sections were detected. The expressions of Cyclin D1,CD44 and the clinical and pathological data were statistically analyzed. Results The expressions of Cyclin D1 and CD44 had higher rates(40. 4% and 53. 8%,respectively) in gastric adenocarcinoma after surgical resection. The low and high expression of Cyclin D1 and CD44 groups showed no statistically significant difference in age,gender,tumor location,lymphnode dissection rang(P > 0. 05). There were statistically significant differences in preoperative serum lactate dehydrogenase(LDH),T staging,N staging,Lauren classification and histological classification(P < 0. 05). The correlation analysis showed that the expressions of Cyclin D1 and CD44 showed a positive correlation with the above indicators(0. 2 < r < 0. 4),and a highly positive correlation with the above indicators with significant difference(r = 0. 736). Conclusion Cyclin D1 and CD44 have higher expression rates in gastric adenocarcinoma tissues,and are weakly correlated with T staging,N staging,Lauren classification and histological classification. Cyclin D1 and CD44 expression was associated with preoperative serum LDH,postoperative T stage,N stage,Lauren classification and histological grade of gastric adenocarcinoma,but all were correlated weakly. expression of Cyclin D1 is correlated with that of CD44 strongly.
Objective To explore the correlation between expression of Cyclin D1,CD44 and clinicopathological characteristics of patients with radical resection of gastric adenocarcinoma.Methods A total of 104 patients with gastric adenocarcinoma after radical resection were selected,the expressions of Cyclin D1,CD44 in gastric adenocarcinoma tissues in the pathological wax block sections were detected. The expressions of Cyclin D1,CD44 and the clinical and pathological data were statistically analyzed. Results The expressions of Cyclin D1 and CD44 had higher rates(40. 4% and 53. 8%,respectively) in gastric adenocarcinoma after surgical resection. The low and high expression of Cyclin D1 and CD44 groups showed no statistically significant difference in age,gender,tumor location,lymphnode dissection rang(P > 0. 05). There were statistically significant differences in preoperative serum lactate dehydrogenase(LDH),T staging,N staging,Lauren classification and histological classification(P < 0. 05). The correlation analysis showed that the expressions of Cyclin D1 and CD44 showed a positive correlation with the above indicators(0. 2 < r < 0. 4),and a highly positive correlation with the above indicators with significant difference(r = 0. 736). Conclusion Cyclin D1 and CD44 have higher expression rates in gastric adenocarcinoma tissues,and are weakly correlated with T staging,N staging,Lauren classification and histological classification. Cyclin D1 and CD44 expression was associated with preoperative serum LDH,postoperative T stage,N stage,Lauren classification and histological grade of gastric adenocarcinoma,but all were correlated weakly. expression of Cyclin D1 is correlated with that of CD44 strongly.
引文
[1] Ibrahim H M,AbdElbary A M,Mohamed S Y et al. Prognostic Value of Cyclin D1 and CD44 Expression in Gastric Adenocarcinoma[J]. Journal of Gastrointestinal Cancer,2018(9):1-10.
[2]张纯慧,刘霞,徐京京,等. 633例胃癌患者临床病理特征及生存分析[J].实用肿瘤学杂志,2017,31(5):396-404.
[3]张文昭,曹风华,陶才华.胃癌患者血清和癌组织中LDH的表达与其预后的相关性分析[J].国际检验学杂志,2017,38(7):995-997.
[4]高小妹,张凯莉,郁新新,等.干细胞在实体肿瘤转移中的作用与地位[J].复旦学报:医学版,2016,43(1):81-85.
[5] Zoller M. CD44:can a cancer-initiating cell profit from an abundantly expressed molecule[J]. Nature Reviews Cancer,2011,11(4):254-267.
[6] Liu D,Sun J,Zhu J,et al. Expression and clinical significance of colorectal cancer stem cell marker EpCAMhigh/CD44+in colorectal cancer[J]. Oncol Lett,2014(7):1544-1548.
[7] Casasola S V,Menéndez M J,Martínez O A,et al. Prognostic value of clinicopathologic factors Ki67,cyclin D1,cyclin D3and CDK4 in gastric carcinoma[J]. Oncologia,2004,27(9):537-543.
[8] Senel F,K9kenek Unal T D,Karaman H,et al. Prognostic Value of Cancer Stem Cell Markers CD44 and ALDH1/2 in Gastric Cancer Cases[J]. Asian Pacific Journal of Cancer Prevention,2017,18(9):2527-2531.
[9]黄名威,吴留成,覃宇周,等. HIF-1、CD44在胃癌组织中的表达及临床意义[J].中国癌症防治杂志,2016,8(6):360-364.
[10] Casasola S V,Menéndez M J,Martínez O A,et al. Prognostic value of clinicopathologic factors Ki67,cyclin D1,cyclin D3and CDK4 in gastric carcinoma[J]. Oncologia,2004,27(9):537-543.
[11]郑宝军,王红钰,潘立峰,等.信号转导和转录活化因子与细胞周期素D在胃癌组织中的表达及意义[J].中华普通外科杂志,2007,22(8):629-630.
[12] Arici D S,Tuncer E,Ozer H,et al. Expression of retinoblastoma and cyclin D1 in gastric carcinoma[J]. Neoplasma,2009,56(1):63-67.
[13] Takano Y,Kato Y,Masuda M,et al. Cyclin D2,but not cyclin D1,overexpression closely correlates with gastric cancer progression and prognosis[J]. Journal of Pathology,1999,189(2):194-200.
[14] Wang T,Ong C,Shi J,et al. Sequential expression of putative stem cell markers in gastric carcinogenesis[J]. British Journal of Cancer,2011,105(5):658-665.
[15] Yamaguchi A,Goi T,Yu J,et al. Expression of CD44v6 in advanced gastric cancer and its relationship to hematogenous metastasis and long-term prognosis[J]. Journal of Surgical Oncology,2002,79(4):230-235.
[16] Chen Y,Fu Z,Xu S,et al. The prognostic value of the CD44expression in gastric cancer:a Meta-analysis[J]. Biomed Pharmacother,2014,68(6):693-697.
[17]谢建伟,黄昌明,郑朝辉,等.肿瘤干细胞表面标记物CD44在胃癌中的表达及其意义[J].中华胃肠外科杂志,2013,16(11):1107-1112.
[18] Cao X,Cao D,Jin M,et al. CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach[J]. BMC Gastroenterol,2014,14(1):1-7.
[19] Arici S,Kivan9 F,zer H,et al. CD44 and Ki 67 expression in gastric adenocarcinomas(correlation with clinicopathological parameters)[J]. Türk Patoloji Dergisi,2006,22(1):26-31.
[20] Godar S,Ince T A,Bell G W,et al. Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression[J]. Cell,2008,134(1):62-73.
[21] Cheng C,Yaffe M B,Sharp P A. A positive feedback loop couples Ras activation and CD44 alternative splicing[J].Genes Dev,2006,20(13):1715-1720.
[22] Kim Y S,Seo D W,Kong S K,et al. TIMP1 induces CD44expression and the activation and nuclear translocation of SHP1during the late centrocyte/post-germinal center B cell differentiation[J]. Cancer Lett,2008,269(1):37-45.
[23] Li J,Zhou B P. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMTassociated cancer stem cell-like characters[J]. BMC Cancer,2011,11(1):1-11.
[24] X H,Tian Y,Yuan X,et al. The role of CD44 in epithelialmesenchymal transition and cancer development[J]. Onco Targets Ther,2015,8(1):3783-3792.
[25] Liu C,Kelnar K,Liu B,et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44[J]. Nat Med,2011,17(2):211-215.
[26] Yang K,Handorean A M,Iczkowski K A. MicroRNAs 373and 520c are downregulated in prostate cancer,suppress CD44translation and enhance invasion of prostate cancer cells in vitro[J]. Int J Clin Exp Pathol,2009,2(4):361-369.
[27] Cheng W,Liu T,Wan X,et al. MicroRNA-199a targets CD44to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells[J]. FEBS J,2012,279(11):2047-2059.
[28] Chen C H,Cheng C Y,Chen Y C,et al. MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by targeting the CD44 in pressure-induced renal fibrosis[J].PLo S One,2014,9(6):e99802.
[29] Jianfei Luo,Ruicheng Yan,Xiaobo He,et al. SOX2 inhibits cell proliferation and metastasis,promotes apoptotic by downregulating CCND1 and PARP in gastric cancer[J]. Am J Transl Res,2018,10(2):639-647.
[30] Azarhoosh R,Ebneghasem R,Besharat S. HER-2/neu gene amplification in gastric adenocarcinoma and its relationship with clinical and pathological findings[J]. Journal of Gastrointestinal Oncology,2017,8(6):1046-1050.
[31] Wu S,He H,Liu H,et al. C-C motif chemokine 22 predicts postoperative prognosis and adjuvant chemotherapeutic benefits in patients with stageⅡ/Ⅲgastric cancer[J]. Oncoimmunology,2018,7(6):e1433517.
[32] Obermannova R,Redova-Lojova M,Vychytilova-Faltejskova P,et al. Tumor Expression of miR-10b,miR-21,miR-143and miR-145 Is Related to Clinicopathological Features of Gastric Cancer in a Central European Population[J]. Anticancer Res,2018,38(6):3719-3724.
[2]张纯慧,刘霞,徐京京,等. 633例胃癌患者临床病理特征及生存分析[J].实用肿瘤学杂志,2017,31(5):396-404.
[3]张文昭,曹风华,陶才华.胃癌患者血清和癌组织中LDH的表达与其预后的相关性分析[J].国际检验学杂志,2017,38(7):995-997.
[4]高小妹,张凯莉,郁新新,等.干细胞在实体肿瘤转移中的作用与地位[J].复旦学报:医学版,2016,43(1):81-85.
[5] Zoller M. CD44:can a cancer-initiating cell profit from an abundantly expressed molecule[J]. Nature Reviews Cancer,2011,11(4):254-267.
[6] Liu D,Sun J,Zhu J,et al. Expression and clinical significance of colorectal cancer stem cell marker EpCAMhigh/CD44+in colorectal cancer[J]. Oncol Lett,2014(7):1544-1548.
[7] Casasola S V,Menéndez M J,Martínez O A,et al. Prognostic value of clinicopathologic factors Ki67,cyclin D1,cyclin D3and CDK4 in gastric carcinoma[J]. Oncologia,2004,27(9):537-543.
[8] Senel F,K9kenek Unal T D,Karaman H,et al. Prognostic Value of Cancer Stem Cell Markers CD44 and ALDH1/2 in Gastric Cancer Cases[J]. Asian Pacific Journal of Cancer Prevention,2017,18(9):2527-2531.
[9]黄名威,吴留成,覃宇周,等. HIF-1、CD44在胃癌组织中的表达及临床意义[J].中国癌症防治杂志,2016,8(6):360-364.
[10] Casasola S V,Menéndez M J,Martínez O A,et al. Prognostic value of clinicopathologic factors Ki67,cyclin D1,cyclin D3and CDK4 in gastric carcinoma[J]. Oncologia,2004,27(9):537-543.
[11]郑宝军,王红钰,潘立峰,等.信号转导和转录活化因子与细胞周期素D在胃癌组织中的表达及意义[J].中华普通外科杂志,2007,22(8):629-630.
[12] Arici D S,Tuncer E,Ozer H,et al. Expression of retinoblastoma and cyclin D1 in gastric carcinoma[J]. Neoplasma,2009,56(1):63-67.
[13] Takano Y,Kato Y,Masuda M,et al. Cyclin D2,but not cyclin D1,overexpression closely correlates with gastric cancer progression and prognosis[J]. Journal of Pathology,1999,189(2):194-200.
[14] Wang T,Ong C,Shi J,et al. Sequential expression of putative stem cell markers in gastric carcinogenesis[J]. British Journal of Cancer,2011,105(5):658-665.
[15] Yamaguchi A,Goi T,Yu J,et al. Expression of CD44v6 in advanced gastric cancer and its relationship to hematogenous metastasis and long-term prognosis[J]. Journal of Surgical Oncology,2002,79(4):230-235.
[16] Chen Y,Fu Z,Xu S,et al. The prognostic value of the CD44expression in gastric cancer:a Meta-analysis[J]. Biomed Pharmacother,2014,68(6):693-697.
[17]谢建伟,黄昌明,郑朝辉,等.肿瘤干细胞表面标记物CD44在胃癌中的表达及其意义[J].中华胃肠外科杂志,2013,16(11):1107-1112.
[18] Cao X,Cao D,Jin M,et al. CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach[J]. BMC Gastroenterol,2014,14(1):1-7.
[19] Arici S,Kivan9 F,zer H,et al. CD44 and Ki 67 expression in gastric adenocarcinomas(correlation with clinicopathological parameters)[J]. Türk Patoloji Dergisi,2006,22(1):26-31.
[20] Godar S,Ince T A,Bell G W,et al. Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression[J]. Cell,2008,134(1):62-73.
[21] Cheng C,Yaffe M B,Sharp P A. A positive feedback loop couples Ras activation and CD44 alternative splicing[J].Genes Dev,2006,20(13):1715-1720.
[22] Kim Y S,Seo D W,Kong S K,et al. TIMP1 induces CD44expression and the activation and nuclear translocation of SHP1during the late centrocyte/post-germinal center B cell differentiation[J]. Cancer Lett,2008,269(1):37-45.
[23] Li J,Zhou B P. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMTassociated cancer stem cell-like characters[J]. BMC Cancer,2011,11(1):1-11.
[24] X H,Tian Y,Yuan X,et al. The role of CD44 in epithelialmesenchymal transition and cancer development[J]. Onco Targets Ther,2015,8(1):3783-3792.
[25] Liu C,Kelnar K,Liu B,et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44[J]. Nat Med,2011,17(2):211-215.
[26] Yang K,Handorean A M,Iczkowski K A. MicroRNAs 373and 520c are downregulated in prostate cancer,suppress CD44translation and enhance invasion of prostate cancer cells in vitro[J]. Int J Clin Exp Pathol,2009,2(4):361-369.
[27] Cheng W,Liu T,Wan X,et al. MicroRNA-199a targets CD44to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells[J]. FEBS J,2012,279(11):2047-2059.
[28] Chen C H,Cheng C Y,Chen Y C,et al. MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by targeting the CD44 in pressure-induced renal fibrosis[J].PLo S One,2014,9(6):e99802.
[29] Jianfei Luo,Ruicheng Yan,Xiaobo He,et al. SOX2 inhibits cell proliferation and metastasis,promotes apoptotic by downregulating CCND1 and PARP in gastric cancer[J]. Am J Transl Res,2018,10(2):639-647.
[30] Azarhoosh R,Ebneghasem R,Besharat S. HER-2/neu gene amplification in gastric adenocarcinoma and its relationship with clinical and pathological findings[J]. Journal of Gastrointestinal Oncology,2017,8(6):1046-1050.
[31] Wu S,He H,Liu H,et al. C-C motif chemokine 22 predicts postoperative prognosis and adjuvant chemotherapeutic benefits in patients with stageⅡ/Ⅲgastric cancer[J]. Oncoimmunology,2018,7(6):e1433517.
[32] Obermannova R,Redova-Lojova M,Vychytilova-Faltejskova P,et al. Tumor Expression of miR-10b,miR-21,miR-143and miR-145 Is Related to Clinicopathological Features of Gastric Cancer in a Central European Population[J]. Anticancer Res,2018,38(6):3719-3724.