Expression And Prognostic Role Of Immune-Related And Drug Resistance-Related Signaling Pathways In Patients With Gastric Cancer

Objective:To review the clinical data and survival information of gastric cancer patientswith radical gastrectomy, and to explore the relationship of clinicopathologicalfeatures, postoperative treatment characteristics and progonisis of these patients.To study the expression of tumor immune-related and drug resistance-relatedfactors in gastric carcinoma, and to discuss the relationship among the abovefactors expression and clinicopathological features and prognosis. We expect tofind a biomarker to predict the patients' immune status, and chemotherapeuticeffect, and the risk of recurrence and metastasis and death. The study willprovide a theoretical basis to predict adjuvant chemotherapy effect andprognosis of gastric cancer.Method:Clinical data of gastric cancer patients who unserwent radical gastrectomy andhad complete follow-up information from January2004to December2006wereanalyzed retrospectively. To analysis the relationship of clinicopathologicalfeatures, postoperative treatment characteristics and progonosis of these patients.The surgical pathological specimens of these patients were made into tissuemicroarray. Expression of IL-6R, JAK1, STAT3, PI3K, AKT and mTOR weredetected in gastric carcinoma by tissue microarray and immunohistochemistry.To analysis the relationship of these markers expression, clinicopathologicalfeatures, postoperative treatment and prognosis by SPSS19.0software package. Resoult:1. All360patients included in the study were gastric cancer with radicalgastrectomy. The median follow-up time was68.9months. Of the360patients,247patients (68.8%) had experienced tumor recurrence and metastasis, and231(64.2%) patients had died by the end of the follow-up date (August1,2011).The DFS was22.2months, and the OS was32.5months. The5-year overallsurvival rates were38.0%.2. Surgical margin, signet ring cell carcinoma, TNMstage and postoperative adjuvant chemotherapy are independent risk factors inpredicting DFS. Surgical margin, signet ring cell carcinoma, Borrmann type,TNM staging and postoperative adjuvant chemotherapy are independent riskfactosr in predicting OS.3. Compared with surgery alone, the cases treated withpostoperative adjuvant chemotherapy had a longer survival time(P＜0.01).Adjuvant chemotherapy with4-6cycles is most reasonable. There is nodifference between the chemotherapy program with oxaliplatin or withdocetaxel (P>0.05). The survival of signet ring cell carcinoma had nodifference between the cases treated with postoperative adjuvant chemotherapyand surgery alone (P>0.05).4. The expression of IL6R,STAT3,JAK1,PI3K,AKT,mTOR had a significant correlation.5. The overexpression of IL6R is anindependent risk factor in predicting DFS and OS. The overexpression of JAK1is an independent risk factor in predicting OS.6. There is no significantdifference in patients' survival between STAT3or JAK1overexpression andweak-expression (P>0.05).7. In the patients with AKT or mTORweak-expression, the cases treated with postoperative adjuvant chemotherapyhad a longer survival time than surgery alone (P＜0.01). While, about thesurvival of the patients with AKT or mTOR overexpression, there is nodifference between the cases treated with postoperative adjuvant chemotherapyand surgery alone (P>0.05).8. In the patients with IL6R, JAK1, AKT andmTOR co-expression three or more, postoperative adjuvant chemotherapy hadno influence to DFS and OS compared with surgery alone(P>0.05). Thesurvival of those patients treated with postoperative adjuvant chemotherapy was not improved or even shorter.Conclusion:Surgical margin, signet ring cell carcinoma, TNM stage and postoperativeadjuvant chemotherapy are independent risk factors in predicting DFS. Surgicalmargin, signet ring cell carcinoma, Borrmann type, TNM staging andpostoperative adjuvant chemotherapy are independent risk factosr in predictingOS. In the patients with IL6R or JAK1overexpression, tumorimmunosuppressive factor, the recurrence and metastasis and death risk areincreased. In these patients with AKT or mTOR overexpression, drugresistance-related markers, there is no difference to DFS and OS betweenpostoperative adjuvant chemotherapy and surgery alone. More importantly, thereis no difference to DFS and OS between postoperative adjuvant chemotherapyand surgery alone in the patients with IL6R, JAK1, AKT and mTORco-expression three or more. These results suggest that the standardpostoperative adjuvant chemotherapy of4-6cycles may improve prognosis ofthe gastric cancer in general, while, simple postoperative adjuvant chemotherapyis not the best choice for the patients with tumor immunosuppression and drugresistance.