Identification Of Multiple Factors For Prognosis And Meta-Analysis Of CircRNAs In The Prognosis Of Gastric Cancer

Purposes:Gastric cancer is the third leading cause of cancer-related deaths worldwide.China is the country with the heaviest burden of gastric cancer in the world.On the one hand,the prognosis of gastric cancer is related to patients'age,gender,histological characteristics,AJCC stage,molecular typing and surgical methods.However,independent risk factors for predicting the survival rate of gastric cancer have not been systematically described,which need to be verified by large sample of follow-up data.We collected large sample data of gastric cancer patients from the surveillance,epidemiology,and end results database?SEER?to investigate the relationship between the epidemiological characteristics and prognosis of gastric cancer.On the other hand,more and more evidences show that novel biomarkers circ RNAs can play an important role in the development of gastric cancer as oncogenes or tumor suppressor genes.The dysregulation of circ RNAs shows prognostic value in gastric cancer.However,due to single center,small sample,different experimental methods and standards for judgment adopted by different research departments,there were significant differences in the results of evaluating the relationship between the expression of circ RNAs and the prognosis of gastric cancer patients.Therefore,the another purpose of this study is to clarify the relationship between the abnormal expression of multiple circ RNAs and the prognosis of gastric cancer patients by meta-analysis,so as to further understand the prognostic value of circ RNAs.According to the results,we can prolong the survival period of gastric cancer patients,improve the quality of life,providing precision treatment and medical humanistic care for high-risk patients.Method:?1?We used SEER database to extract 42966 cases of patients with gastric cancer diagnosed by pathology in 2010-2016,including diagnosis year,age,race,gender,primary site,histologic type,Lauren classification,AJCC 7^th TNM Stage,the surgery on primary site,radiotherapy,chemotherapy,tumor size,marital status,insurance status,distant?lung,brain,bone,liver?metastasis,education,median family income,survival,follow-up months and causes of death.Univariable and multivariable cox regression were used to analyze the independent risk factors affecting the prognosis of gastric cancer patients,and K-M survival analysis of each independent risk factor was made in the end.?2?We researched the articles covering the relationship between circ RNAs and prognosis of gastric cancer published in Pub Med,Cochrane,Embase,Web of science,Wanfang,CNKI and VIP database before December 31,2019.According to our inclusion and exclusion criteria,35 articles were selected for meta-analysis.The quality of each article was evaluated by NOS scale and the heterogeneity test was conducted.Finally,the HR value and 95%CI of overall survival?OS?and disease-free survival?DFS?were obtained by combining the effect size.Result:?1?Elderly?P<0.001?,male?P<0.001?,American Indian/Alaskan Native?P<0.001?,lower grade?P<0.001?,cardia cancer?P<0.001?,mucinous adenocarcinoma?P<0.001?,diffuse-type gastric cancer?P<0.001?,larger tumor size?P<0.001?,more distant metastasis sites?P<0.001?,no surgery on primary tumor sites?P<0.001?,no radiotherapy?P<0.001?,no chemotherapy?P<0.001?,no insurance?P<0.001?,single?P<0.001?,widowed?P<0.001?,poorly education?P<0.001?and lower family income?P<0.001?were the independent risk factors for the prognosis of gastric cancer.?2?Asia/Pacific island residents?P<0.001?,female?P<0.001?,signet ring cell carcinoma?P<0.001?,intestinal-type gastric cancer?P<0.001?,surgery on primary tumor site?P<0.001?,radiotherapy?P<0.001?,chemotherapy?P<0.001?,preoperative and postoperative adjuvant radiotherapy?P<0.001?,insurance?P<0.001?,married?P<0.001?,highly educated?P<0.001?and higher family income?P=0.001?were independent protective factors for the prognosis of gastric cancer.?3?The total HR values?95%CI?of OS and DFS related to highly expressed circ RNAs?eg,circ?0009910,has?circ?0000467,has?circ?0065149,has?circ?0081143,circ DLST?which can function as oncogene were 1.83?1.64-2.03?,P<0.001 and 1.66?1.33-2.07?,P<0.001,respectively.?4?The total HR?95%CI?of OS and DFS related to highly expressed circ RNAs?eg,circ SMARCA5?circ LMTK2?has?circ?0001017?has?circ?0061276?circ-KIAA1244?which can function as tumor suppressor genes was 0.54?0.45-0.66?,P<0.001 and 0.58?0.43-0.78?,P<0.001,respectively.Conclusion:?1?The overall prognosis of patients with gastric cancer was poor?median survival time is16 months?.Patient with following risk factors may indicate poor prognosis:elderly,male,American Indian/Alaskan native,lower grade,cardia cancer,mucinous adenocarcinoma,diffuse-type gastric cancer,larger tumor size,more distant metastasis sites,no surgery on the primary tumor site,no chemotherapy,no radiotherapy,no insurance,single,widowed,poorly education,lower family income.Our research can help clinicians identify high-risk patients in the diagnosis and treatment process,provide more effective medical care,help patients to prolong the life time and improve the quality of life.?2?The dysregulation of circ RNAs?eg,circ?0009910?has?circ?0000467?has?circ?0065149?has?circ?0081143?circ DLST?circ SMARCA5?circ LMTK2?has?circ?0001017?has?circ?0061276?circ-KIAA1244?can be used as potential tumor biomarkers in patients with gastric cancer.By detecting the expression level of specific circ RNAs in tissues or other body fluids,we can not only make appropriate clinical decisions according to different prognosis,but also monitor the therapeutic effect of gastric cancer patients who received different treatment.