伴微乳头结构的肺腺癌组织中EGFR及KRAS的表达变化及意义
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摘要
目的探讨表皮生长因子受体(EGFR)、鼠Kirsten肉瘤病毒致癌基因(KRAS)表达与伴微乳头结构的肺腺癌患者临床病理参数间的关系。方法采用SP免疫组织化学染色方法检测伴微乳头结构的肺腺癌组织及对应癌旁正常组织中EGFR及KRAS蛋白的表达,运用Western blot法检测伴微乳头结构的肺腺癌组织及对应癌旁正常组织中EGFR及KRAS蛋白的表达量,并分析EGFR及KRAS蛋白阳性表达情况与患者临床病理特征的关系,采用Spearman等级相关分析EGFR及KRAS在伴微乳头结构的肺腺癌组织中表达的相关性。结果伴微乳头结构的肺腺癌组织中的EGFR与KRAS蛋白表达阳性率分别为74. 4%(67/90)、83. 3%(75/90),明显高于癌旁正常组织的15. 2%(7/46)、19. 6%(9/46)(P=0. 025,0. 018)。癌组织中EGFR、KRAS蛋白表达水平分别为0. 7136±0. 0652、0. 8751±0. 0347,明显高于癌旁正常组织的0. 2148±0. 0124、0. 2308±0. 0136 (P=0. 032,0. 029)。EGFR蛋白阳性表达率与TNM分期、淋巴结转移有关(P=0. 022,0. 015),KRAS蛋白阳性表达率与TNM分期、分化程度、淋巴结转移有关(P=0. 017,0. 024,0. 011)。经Spearman相关分析显示,癌组织中EGFR与KRAS表达呈正相关(r=0. 516,P=0. 023)。结论 EGFR、KRAS蛋白表达在伴微乳头结构的肺腺癌组织中明显上调,且两者呈正相关的关系,在伴微乳头结构的肺腺癌发生及发展中具有重要作用。EGFR、KRAS检测可以作为早期诊断伴微乳头结构的肺腺癌的生物学指标。
Objective To investigate the relationship between the expression of epidermal growth factor receptor( EGFR) and Kirsten sarcoma virus oncogene( KRAS) and clinicopathological parameters in patients with lung adenocarcinoma with micro papillary structure. Methods The expression of EGFR and KRAS protein in lung adenocarcinoma tissues and corresponding micro papillary carcinoma of adjacent normal tissues was detected by SP immunohistochemistry,and the expression level of EGFR and KRAS protein was detected by Western blot assay. The relationship between the expression of EGFR and KRAS protein and clinicopathological features was analyzed by Spearman grade. Results The positive rate of EGFR and KRAS protein expression in lung adenocarcinoma tissues with micro papilla structure were 74. 4%( 67/90) and 83. 3%( 75/90),respectively,which were significantly higher than those in adjacent normal tissues( 15. 2%( 7/46) and 19. 6%( 9/46)( P = 0. 025,0. 018). The expression levels of EGFR and KRAS in cancer tissues were 0. 7136 ± 0. 0652 and 0. 8751 ± 0. 0347,which were significantly higher than those in adjacent normal tissues,which were 0. 2148 ± 0. 0124 and 0. 2308 ± 0. 0136( P = 0. 032,0. 029). The positive expression rate of EGFR protein was related to TNM stage and lymph node metastasis( P =0. 022,0. 015). The positive expression rate of KRAS protein was related to TNM stage,differentiation degree and lymph node metastasis( P = 0. 017,0. 024,0. 011). Spearman correlation analysis showed that the expression of EGFR in cancer tissues was positively correlated with the expression of KRAS( r = 0. 516,P = 0. 023). Conclusion The expression of EGFR and KRAS protein is significantly up-regulated in lung adenocarcinoma tissues with micro papillary structure,and has a positive correlation with them. It plays an important role in the occurrence and development of lung adenocarcinoma with micro papilla structure. The detection of EGFR and KRAS can be used as a biological marker for early diagnosis of lung adenocarcinoma with micro papillary structure.
Objective To investigate the relationship between the expression of epidermal growth factor receptor( EGFR) and Kirsten sarcoma virus oncogene( KRAS) and clinicopathological parameters in patients with lung adenocarcinoma with micro papillary structure. Methods The expression of EGFR and KRAS protein in lung adenocarcinoma tissues and corresponding micro papillary carcinoma of adjacent normal tissues was detected by SP immunohistochemistry,and the expression level of EGFR and KRAS protein was detected by Western blot assay. The relationship between the expression of EGFR and KRAS protein and clinicopathological features was analyzed by Spearman grade. Results The positive rate of EGFR and KRAS protein expression in lung adenocarcinoma tissues with micro papilla structure were 74. 4%( 67/90) and 83. 3%( 75/90),respectively,which were significantly higher than those in adjacent normal tissues( 15. 2%( 7/46) and 19. 6%( 9/46)( P = 0. 025,0. 018). The expression levels of EGFR and KRAS in cancer tissues were 0. 7136 ± 0. 0652 and 0. 8751 ± 0. 0347,which were significantly higher than those in adjacent normal tissues,which were 0. 2148 ± 0. 0124 and 0. 2308 ± 0. 0136( P = 0. 032,0. 029). The positive expression rate of EGFR protein was related to TNM stage and lymph node metastasis( P =0. 022,0. 015). The positive expression rate of KRAS protein was related to TNM stage,differentiation degree and lymph node metastasis( P = 0. 017,0. 024,0. 011). Spearman correlation analysis showed that the expression of EGFR in cancer tissues was positively correlated with the expression of KRAS( r = 0. 516,P = 0. 023). Conclusion The expression of EGFR and KRAS protein is significantly up-regulated in lung adenocarcinoma tissues with micro papillary structure,and has a positive correlation with them. It plays an important role in the occurrence and development of lung adenocarcinoma with micro papilla structure. The detection of EGFR and KRAS can be used as a biological marker for early diagnosis of lung adenocarcinoma with micro papillary structure.
引文
[1]董宇杰,张莉,周立娟,等.伴微乳头结构肺腺癌的临床病理特征及预后分析[J].诊断病理学杂志,2017,24(6):445-449.
[2] AMIN M B,TAMBOLI P,MERCHANT S H,et al. Micropapillary component in lung adenocarcinoma:A distinctive histologic feature with possible prognostic significance[J]. Am J Surg Pathol,2002,26(3):358-364.
[3]石祥宇,庞青松,赵纲,等.伴微乳头结构肺腺癌的研究进展[J].中国肺癌杂志,2015,18(11):701-705.
[4]李嫣,汤小晗.表皮生长因子受体信号通路对卵巢癌细胞自噬的调控[J].国际妇产科学杂志,2017,44(2):133-136.
[5]曹田宇,杜风,李婷宇,等. miR-139-5p调控KRAS突变结直肠癌细胞增殖、迁移和侵袭的功能与机制研究[J].山西医科大学学报,2017,48(4):322-328.
[6]乐露露,傅芬.上皮性卵巢癌组织中EGFR、KRAS的表达变化及意义[J].山东医药,2011,51(46):16-18.
[7]潘立萍,苏冬菊,鲍永霞,等. EHD1与EGFR异常表达在NSCLC临床诊治中的研究进展[J].现代肿瘤医学,2017,25(4):669-672.
[8]林吉兴,王柏霖,刘阳,等.粒状头样2和表皮生长因子受体蛋白在食管鳞癌中的表达及预后判断价值[J].解放军医学院学报,2017,38(5):440-444.
[9]涂长玲,朱颖,董坚,等.晚期非小细胞肺癌循环肿瘤细胞EGFR表达与细胞免疫的相关性研究[J].西部医学,2016,28(9):1221-1226.
[10]陈寿松,肖同浩,陈昕薇,等. EGFR、COX-2及P63蛋白在非小细胞肺癌中的表达及其意义[J].第三军医大学学报,2008,30(7):628-630.
[11]孙光远,赵学维,李兵,等. EGFR在女性非小细胞肺癌中的表达及临床意义[J].中国癌症杂志,2007,17(5):380-384.
[12]蒋丽,张丽,彭韬,等.表皮生长因子受体信号通路调控人肝细胞癌细胞增殖分子机制的研究[J].南京医科大学学报(自然科学版),2007,27(6):523-526,封2.
[13]鲍晨,王一理,柳俊,等. EGFR和KRAS在上皮性卵巢癌组织中的表达及临床意义[J].现代生物医学进展,2017,17(5):892-894,922.
[14] MISHRA N,TIMILSINA U,GHIMIRE D,et al. Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells[J]. Biochem Biophys Res Commun,2017,482(4):713-719.
[15] SUN Q,JIANG C W,TAN Z H,et al. MiR-222 promotes proliferation,migration and invasion of lung adenocarcinoma cells by targeting ETS1[J]. Eur Rev Med Pharmacol Sci,2017,21(10):2385-2391.
[2] AMIN M B,TAMBOLI P,MERCHANT S H,et al. Micropapillary component in lung adenocarcinoma:A distinctive histologic feature with possible prognostic significance[J]. Am J Surg Pathol,2002,26(3):358-364.
[3]石祥宇,庞青松,赵纲,等.伴微乳头结构肺腺癌的研究进展[J].中国肺癌杂志,2015,18(11):701-705.
[4]李嫣,汤小晗.表皮生长因子受体信号通路对卵巢癌细胞自噬的调控[J].国际妇产科学杂志,2017,44(2):133-136.
[5]曹田宇,杜风,李婷宇,等. miR-139-5p调控KRAS突变结直肠癌细胞增殖、迁移和侵袭的功能与机制研究[J].山西医科大学学报,2017,48(4):322-328.
[6]乐露露,傅芬.上皮性卵巢癌组织中EGFR、KRAS的表达变化及意义[J].山东医药,2011,51(46):16-18.
[7]潘立萍,苏冬菊,鲍永霞,等. EHD1与EGFR异常表达在NSCLC临床诊治中的研究进展[J].现代肿瘤医学,2017,25(4):669-672.
[8]林吉兴,王柏霖,刘阳,等.粒状头样2和表皮生长因子受体蛋白在食管鳞癌中的表达及预后判断价值[J].解放军医学院学报,2017,38(5):440-444.
[9]涂长玲,朱颖,董坚,等.晚期非小细胞肺癌循环肿瘤细胞EGFR表达与细胞免疫的相关性研究[J].西部医学,2016,28(9):1221-1226.
[10]陈寿松,肖同浩,陈昕薇,等. EGFR、COX-2及P63蛋白在非小细胞肺癌中的表达及其意义[J].第三军医大学学报,2008,30(7):628-630.
[11]孙光远,赵学维,李兵,等. EGFR在女性非小细胞肺癌中的表达及临床意义[J].中国癌症杂志,2007,17(5):380-384.
[12]蒋丽,张丽,彭韬,等.表皮生长因子受体信号通路调控人肝细胞癌细胞增殖分子机制的研究[J].南京医科大学学报(自然科学版),2007,27(6):523-526,封2.
[13]鲍晨,王一理,柳俊,等. EGFR和KRAS在上皮性卵巢癌组织中的表达及临床意义[J].现代生物医学进展,2017,17(5):892-894,922.
[14] MISHRA N,TIMILSINA U,GHIMIRE D,et al. Downregulation of cytochrome c oxidase subunit 7A1 expression is important in enhancing cell proliferation in adenocarcinoma cells[J]. Biochem Biophys Res Commun,2017,482(4):713-719.
[15] SUN Q,JIANG C W,TAN Z H,et al. MiR-222 promotes proliferation,migration and invasion of lung adenocarcinoma cells by targeting ETS1[J]. Eur Rev Med Pharmacol Sci,2017,21(10):2385-2391.