胰腺癌炎性微环境与细胞上皮间质转化的关系及意义

Relationship between inflammatory microenvironment and epithelial-mesenchymal transition and its significance in pancreatic carcinoma

目的探讨胰腺癌炎性微环境与细胞上皮间质转化(EMT)的关系及两者对患者的影响。方法回顾性分析2015年6月至2016年6月收治并手术治疗的53例胰腺癌患者的临床与病理资料,包括转移癌31例和原位癌22例,取癌旁正常组织为对照,采用免疫组织化学实验测定EMT标志物E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(Ncadherin)的表达,采用酶联免疫吸附法(ELISA)测定肿瘤炎性微环境标志物白介素6(IL-6)、核因子κB(NF-κB)、信号转导子与转录激活子3(STAT3)、肿瘤坏死因子α(TNF-α)水平。结果 IL-6、NF-κB、STAT3、TNF-α局部组织中含量转移癌>原位癌>对照组(P<0. 01);局部组织中E-cadherin阳性表达率转移癌<原位癌<对照组(P<0. 01);N-cadherin阳性表达率转移癌>原位癌>对照组(P<0. 01)。根据具体阳性表达情况将53患者进一步分为E-cadherin阴性且N-cadherin阳性组(E^-/N^+) 29例,E-cadherin与N-cadherin共阳性组(E^+/N^+) 13例、E-cadherin阳性且N-cadherin阴性组(E^+/N^-) 11例。IL-6、NF-κB、STAT3、TNF-α局部组织中含量E^-/N^+组>E^+/N^+组>E^+/N^-组(P<0.01)。患者术后1年生存率为26. 4%。癌组织IL-6(P=0. 001)、NF-κB(P=0. 005)、STAT3(P=0. 004)、TNF-α(P=0. 007)含量对预后均有较高的预测价值,最佳工作点分别为51. 87 nmol/g、5. 44 nmol/g、6. 78 nmol/g和17. 95nmol/g。E^-/N^+(P=0. 004)、IL-6>51. 87 nmol/g(P=0. 026)、NF-κB>5. 44 nmol/g(P=0. 018)、STAT3>6. 78 nmol/g(P=0. 021)与TNF-α>17. 95 nmol/g(P=0. 042)患者的术后生存期明显偏短。结论胰腺癌的肿瘤炎性微环境与EMT之间可能存在相互作用,共同促进了胰腺癌发生与发展。

Objective To explore the relationship between inflammatory microenvironment and epithelial-mesenchymal transition (EMT)and their effects on the prognosis of patients with pancreatic carcinoma.Methods The clinical,and pathological data of 53patients with pancreatic cancer receiving surgical treatment from June 2015to June 2016were analyzed retrospectively,including 31cases of metastatic carcinoma and 22cases of situ carcinoma.Normal tissues adjacent to cancer were taken as controls.E-cadherin and N-cadherin expressions of EMT markers were detected by immunohistochemistry,and levels of interleukin 6(IL-6),nuclear factor-κB (NF-κB ),signal transducers and transcriptional activators 3(STAT3)and tumor necrosis factor α (TNF-α)of inflammatory microenvironment markers were detected by enzyme-linked immunoadsorbant assays (ELISA).Results The contents of IL-6,NF-B,STAT3 and TNF-α in the local tissue of metastatic carcinoma were higher than those in situ carcinoma,and those in situ carcinoma were higher than those in control group (all P <0.01).The positive expression rate of E-cadherin in metastatic carcinoma was lower than that in situ carcinoma,and it in situ carcinoma was lower than that in controls(all P <0.01).The positive expression rate of N-cadherin was metastatic carcinoma >carcinoma in situ >control group (all P <0.01).According to the specific positive expression,53patients were further divided into E-cadherin negative and N-cadherin positive group (E^-/ N^+,n =29),E-cadherin and N-cadherin co-positive group (E^+/N^+,n =13),E-cadherin positive and N-cadherin negative group (E^+/N^-,n =11).The contents of IL-6,NF-κB ,STArI3and TNF-α in the local tissues presented E^-/N^+ group > E^-/N^+ group >E ~/N -group (all P <0.01).The one-year survival rate after operation was 26.4%.The contents of IL-6(P =0.001),NF-κB (P =0.005),STAT3(P =0.004)and TNF-α (P =0.007)in cancer tissues had high predictive value for prognosis,and their optimal cut-off values were 51.87nmol/g,5.44nmol/g,6.78nmol/g,17.95nmol/g respectively.The postoperative survival period of patients with E^-/N^+(P =0.004),IL-6>51.87nmol/g (P =0.026), NF-κB >5.44nmol/g (P =0.018),STA33>6.78nmol/g (P =0.021)and TNF-α>17.95nmol/g (P =0.042)was significantly shorter.Conclusion There may be interaction between inflammatory micro-environment and EMT in pancreatic cancer,which may promote the occurrence and development of pancreatic cancer.