PTEN与TGF-β1在上皮性卵巢癌中的表达及临床意义
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摘要
目的探讨第10号染色体缺失的磷酸酶和张力蛋白同源物基因(phosphatase and tension homolog deleted on chromosome ten, PTEN)、转化生长因子β1(transforming growth factorβ1, TGF-β1)在上皮性卵巢癌患者中的表达及临床意义。方法选取我院2015年1月—2017年12月收治的上皮性卵巢癌100例作为上皮性卵巢癌组,另选取同期收治的卵巢良性肿瘤40例作为卵巢良性肿瘤组。采用免疫组织化学染色法分析PTEN与TGF-β1在上皮性卵巢癌和卵巢良性肿瘤组织中的表达情况,并探讨PTEN、TGF-β1与上皮性卵巢癌病情程度的关系以及二者阳性表达的相关性。结果 PTEN在上皮性卵巢癌组织中的阳性表达率为38.00%低于卵巢良性肿瘤组织中的80.00%(P<0.01);TGF-β1在上皮性卵巢癌组织中的阳性表达率为76.00%明显高于卵巢良性肿瘤组织中的40.00%(P<0.01)。TGF-β1在Ⅲ～Ⅳ期上皮性卵巢癌组织中的阳性表达率为88.24%高于Ⅰ～Ⅱ期上皮性卵巢癌组织中的50.00%(P<0.01);PTEN在Ⅰ～Ⅱ期上皮性卵巢癌组织中的阳性表达率为65.62%明显高于Ⅲ～Ⅳ期上皮性卵巢癌组织中的25.00%,在有淋巴结转移的上皮性卵巢癌组织中的阳性表达率为28.12%低于无淋巴结转移的上皮性卵巢癌组织中的55.56%,差异均有统计学意义(P<0.01)。PTEN与TGF-β1在上皮性卵巢癌组织中的表达呈负相关(r=-0.235,P=0.018)。结论 TGF-β1参与上皮性卵巢癌的发生,并与上皮性卵巢癌病情进展密切相关。TGF-β1过度表达伴随PTEN表达下降或部分缺失,与上皮性卵巢癌的发生发展、细胞耐药密切相关。
Objective To investigate the expressions of phosphatase and tensin homolog deleted on chromosome 10(PTEN), and transforming growth factor β1(TGF-β1) in patients with epithelial ovarian cancer(OvCa) and their clinical significance. Methods A total of 100 cases with epithelial OvCa admitted to our hospital from January 2015 to December 2017 were selected as the epithelial OvCa group, and 40 cases with benign ovarian tumors admitted during the same period were selected as the benign ovarian tumor group. Immunohistochemical staining(immunohistochemistry) was used to analyze the expressions of PTEN and TGF-1 in epithelial OvCa and benign ovarian tumor tissues, and to explore the relationship between PTEN and TGF-1 and the severity of epithelial OvCa and the correlation between their positive expressions. Results The positive expression rate of PTEN in epithelial OvCa tissue was 38.00%, lower than that in benign ovarian tumor tissue(80.0%,P<0.01). The positive expression rate of TGF-β1 in epithelial OvCa tissue was 76.00%, significantly higher than that of 40.00% in the benign ovarian tumor tissue(P<0.01). In stage Ⅲ-Ⅳ epithelial OvCa tissue, the positive expression rate was 88.24%, which was higher than that(50.00%) of stageⅠ-Ⅱ(P< 0.01). Positive expression rate of PTEN in stageⅠ-Ⅱ epithelial OvCa was 65.62%, which was significantly higher than that(25.00%) in stage Ⅲ-Ⅳ epithelial OvCa tissue. In epithelial OvCa tissues with lymph node metastasis, the positive expression rate was 28.12%, which was lower than 55.56% without lymph node metastasis(P<0.01). PTEN was negatively correlated with the expression of TGF-β1 in epithelial OvCa(r=-0.235, P=0.018). Conclusion TGF-β1 is involved in the development of epithelial OvCa and is closely related to the progression of epithelial OvCa. Overexpression of TGF-β1 is associated with decreased expression or partial deletion of PTEN, which is closely related to the occurrence and development of epithelial OvCa as well as drug resistance.
Objective To investigate the expressions of phosphatase and tensin homolog deleted on chromosome 10(PTEN), and transforming growth factor β1(TGF-β1) in patients with epithelial ovarian cancer(OvCa) and their clinical significance. Methods A total of 100 cases with epithelial OvCa admitted to our hospital from January 2015 to December 2017 were selected as the epithelial OvCa group, and 40 cases with benign ovarian tumors admitted during the same period were selected as the benign ovarian tumor group. Immunohistochemical staining(immunohistochemistry) was used to analyze the expressions of PTEN and TGF-1 in epithelial OvCa and benign ovarian tumor tissues, and to explore the relationship between PTEN and TGF-1 and the severity of epithelial OvCa and the correlation between their positive expressions. Results The positive expression rate of PTEN in epithelial OvCa tissue was 38.00%, lower than that in benign ovarian tumor tissue(80.0%,P<0.01). The positive expression rate of TGF-β1 in epithelial OvCa tissue was 76.00%, significantly higher than that of 40.00% in the benign ovarian tumor tissue(P<0.01). In stage Ⅲ-Ⅳ epithelial OvCa tissue, the positive expression rate was 88.24%, which was higher than that(50.00%) of stageⅠ-Ⅱ(P< 0.01). Positive expression rate of PTEN in stageⅠ-Ⅱ epithelial OvCa was 65.62%, which was significantly higher than that(25.00%) in stage Ⅲ-Ⅳ epithelial OvCa tissue. In epithelial OvCa tissues with lymph node metastasis, the positive expression rate was 28.12%, which was lower than 55.56% without lymph node metastasis(P<0.01). PTEN was negatively correlated with the expression of TGF-β1 in epithelial OvCa(r=-0.235, P=0.018). Conclusion TGF-β1 is involved in the development of epithelial OvCa and is closely related to the progression of epithelial OvCa. Overexpression of TGF-β1 is associated with decreased expression or partial deletion of PTEN, which is closely related to the occurrence and development of epithelial OvCa as well as drug resistance.
引文
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[18] 赵红霞.PTEN与肿瘤的相关性研究进展[J].武汉大学学报(医学版),2014,35(1):155-159.
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[3] Liang H,Chen X,Yin Q,et al.PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription[J].Nat Commun,2017,8:14771.
[4] 陈贵巧,于晶,王云慧,等.转化生长因子-β诱导基因表达与肿瘤相关性研究[J].临床军医杂志,2018,46(11):1389-1391.
[5] 赵轩宇,孔为民,商若天,等.子宫内膜癌1971年临床分期与FIGO2009年手术病理分期比较[J].肿瘤学杂志,2019,25(1):51-54.
[6] Yen E Y,Miaw S C,Yu J S,et al.Exosomal TGF-β1 is correlated with lymphatic metastasis of gastric cancers[J].Am J Cancer Res,2017,7(11):2199-2208.
[7] He Z,Chen A Y,Rojanasakul Y,et al.Gallic acid,a phenolic compound,exerts anti-angiogenic effects via the PTEN/AKT/HIF-1α/VEGF signaling pathway in ovarian cancer cells[J].Oncol Rep,2016,35(1):291-297.
[8] 黄海玉,刘小乐,陈衡,等.PTEN和FHIT在上皮性卵巢肿瘤中的表达及其临床意义[J].中国妇幼保健,2010,25(5):654-656.
[9] 张俊,张阳,夏晓艾,等.PTEN表达与中国女性卵巢癌相关性的Meta分析[J].实用妇科内分泌杂志(电子版),2018,5(19):145-146.
[10] 顾建建,李国利.PTEN基因及其在卵巢癌中的研究进展[J].中国肿瘤,2006,15(9):604-607.
[11] Estenva F J,Guo H,Zhang S,et al.PTEN,PIK3CA,p-AKT,and p-p70S6K status:association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer[J].Am J Pathol,2010,177(4):1647-1656.
[12] 张刚,李中,林晓萌,等.乳腺癌组织中PTEN、p-Akt蛋白表达变化及相关性分析[J].山东医药,2014,54(19):48-49.
[13] Dhar S,Kumar A,Li K,et al.Resveratrol regulates PTEN/Aktpathway through inhibition of MTA1 /HDAC unit of the NuRD complexin prostate cancer[J].Biochim Biophys Acta,2015,1853(2):265-275.
[14] Lim H J,Crowe P,Yang J L.Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer[J].J Cancer Res Clin Oncol,2015,141(4):671-689.
[15] Timsah Z,Ahmed Z,Ivan C,et al.Grb2 depletion under non-stimulated conditions inhibits PTEN,promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer[J].Oncogene,2016,35(17):2186-2196.
[16] Kang S,Dong S M,Park N H.Frequent promoter hypermethylation of TGFBI in epithelial ovarian cancer[J].Gynecol Oncol,2010,118(1):58-63.
[17] 马颖,杨向红,田保玲,等.大肠肿瘤中PTEN和TGF-β1表达及意义[J].中国组织化学与细胞化学杂志,2012,21(1):53-56.
[18] 赵红霞.PTEN与肿瘤的相关性研究进展[J].武汉大学学报(医学版),2014,35(1):155-159.