| BACKGROUNDAccording to the latest statistics data from National Cancer Center,gastric cancer ranks third in terms of tumor incidence rate and mortality in China.In 2016,396500 people in China suffered from gastric cancer,and 288500 died from it.Due to the lack of effective and economical methods for early diagnosis of gastric cancer,research on the natural history of this disease has shown that locally advanced gastric cancer in TNM staging II and Ⅲ accounts for the vast majority of the total gastric cancer population.Moreover,some gastric cancer patients are diagnosed with peritoneal metastasis,leading to poor prognosis.The current treatment method for gastric cancer is a multidisciplinary comprehensive treatment leading by operation.Unlike radiotherapy and chemotherapy,comprehensive treatment methods based on operation have great potential in the treatment of gastric cancer patients(such as sustained-release fluorouracil implants and hyperthermic intraperitoneal chemotherapy).However,the safety and effectiveness of these comprehensive treatment methods need to be further clarified.AIM:Exploring whether sustained-release fluorouracil implants can benefit long-term survival in patients with stage Ⅱ and Ⅲ gastric cancer through real-world databases.Evaluate the safety and effectiveness of hyperthermic intraperitoneal chemotherapy in gastric cancer patients by using laboratory examination indicators.METHOD:This study collected the clinicopathological data of patients treated with fluorouracil implants or hyperthermic intraperitoneal chemotherapy in Chinese Academy of Medical Sciences Cancer Hospital.As well as,included gastric cancer patients who received conventional treatment as control.In the study of fluorouracil implants,patients were divided into fluorouracil implants treatment group and non-fluorouracil implants treatment group.The main endpoint of this study is the overall five-year survival of these patients.In the study of hyperthermic intraperitoneal chemotherapy,patients were divided into operation group and non-operation group.Further we compared the laboratory examination results before and after treatment to determine the safety of hyperthermic intraperitoneal chemotherapy.Then we included gastric cancer patients who have not received hyperthermic intraperitoneal chemotherapy for survival comparison to determine the effectiveness of hyperthermic intraperitoneal chemotherapy.All studies used the Kaplan-Meier curve to compare the overall survival of gastric cancer patients,and Cox regression analysis was used to explore the prognostic factors of patients in patients.RESULT:According to the patient admission and exclusion standards,fluorouracil implant study ultimately included a total of 309 locally advanced gastric cancer patients(stages II and Ⅲ).The average age of all patients was 58.25 years old,with 219(70.9%)male and 56(18.1%)of them received neoadjuvant chemotherapy.There are 191(61.8%)patients in TNM stage Ⅲ.All gastric cancer patients underwent R0 radical resection and standard D2 lymph node resection.According to whether fluorouracil implants were used,158 patients were included in the fluorouracil implants treatment group,while the other 161 patients were included in the non-fluorouracil implants treatment group.Postoperative complication rate in fluorouracil implants treatment group was 10.81%,while in nonfluorouracil implants treatment group it was 16.46%.There was no significant statistically difference in the incidence of complications between these two groups(P>0.05).There was no significant difference in overall survival rate between two groups patients and subgroups(P>0.05),Finally,we used multivariate Cox analysis,it was found that in the patient cohort of this study,only N stage and neoadjuvant therapy were independent influencing factors for predicting prognosis.A total of 63 gastric cancer patients who received hyperthermic intraperitoneal chemotherapy were collected.The average age of patients was 54.84 years old,and 68.3%of them were male.In addition,79.4%of patients had a Peritoneal Cancer Index(PCI)score of≤7,and 61.9%of patients had completeness of cytoreduction score of CC-0.Due to the presence of peritoneal metastasis,29 patients(46.03%)were diagnosed as stageⅣ.The laboratory examination results showed that the tumor markers CEA and CA724 in the surgical group decreased more(P<0.001).Meanwhile,there were also more changes in hemoglobin and D-dimer after surgery(P<0.001).These results indicated that changes in these indicators are mainly related to surgical treatment.Comparison of laboratory examination results before and after hyperthermic intraperitoneal chemotherapy for patients showed that it did not cause injured to liver and kidney function(P>0.05).However,hyperthermic intraperitoneal chemotherapy can affect the patient’s blood electrolyte levels.The level of Ca2+ after treatment is lower than the normal range.Reminder for doctors to be vigilant about the occurrence of hypocalcemia in patients.The more decreased CA242 levels were observed in patients receiving hyperthermic intraperitoneal chemotherapy suggests that CA242 may be a sensitive indicator of response to this treatment effect.The improvement in KPS scores among all patients showed statistical differences(P=0.002),indicating that hyperthermic intraperitoneal chemotherapy is safe for gastric cancer patients.However,by comparing the survival status of patients who did not receive hyperthermic intraperitoneal chemotherapy,we did not observe that this treatment can bring survival benefits to gastric cancer patients.Cox regression analysis showed that completeness of cytoreduction score was an independent prognostic factor for these patients(P=0.003).CONCLUSION:Using intraoperative fluorouracil sustained-release chemotherapy do not improve the 5-year survival rate of locally advanced gastric cancer patients who undergoing R0 resection.Based on laboratory examination,it has been confirmed that hyperthermic intraperitoneal chemotherapy is safe for gastric cancer patients and the efficiency of the treatment method is worthy of further clinical trial.BACKGROUND:Mitochondria,as cellular energy factories,plays extremely important role in maintaining normal physiological functions of cells.The disorder of mitochondrial function is related to the occurrence and development of many diseases,including cancer.It mainly affects the occurrence and development of tumors through ① mitochondrial genome mutation ② tumor cell metabolic reprogramming ③ mitochondrial quality control mechanism.Moreover,cellular senescence is a basic characteristic of malignant biological behavior of cancer,mitochondrial dysfunction has broad interaction mechanism with cell aging.Targeting tumor cell mitochondria has also become a new direction for cancer targeted therapy.However,further analysis of mitochondrial genes and cellular senescence genes in gastric cancer patients is still needed.AIM:In this study,we studied the transcriptome data of gastric cancer patients from the cancer genome atlas and constructed a prognostic model based on mitochondria and senescence genes.Then we explored the predictive ability of this model for prognosis of gastric cancer patients and the applicable patient population.METHOD:R software was used to download and integrate the transcriptome and clinical data of gastric cancer patients in the cancer genome atlas database.Finally,a total of 448 cases of data were included in the analysis,including 36 normal cases and 412 tumor cases.We collected mitochondrial genes from the MitoCarta3.0 database and cellular senescence genes from the Senmayo dataset and construct the gene expression matrix.Next,Pearson correlation method was used to clarify the gene correlation.Limma package was used to analyze different expression genes between tumor and normal tissues.What’s more,core genes were construct by combining different expression genes and correlation genes.ClusterProfiler package was used to GO and KEGG enrichment analysis on core genes to explore the gene pathways.Then we performed GSEA analysis on all mitochondrial related pathways from the MitoCarta 3.0 database and cellular senescence pathway from the Senmayo dataset.We integrated the patient’s survival time and status with the core gene expression matrix.Then we performed univariate Cox regression analysis and gain prognostic related core genes.Further we used the Lasso algorithm to simplify the Cox regression analysis results and to construct a mitochondrial—senescence related genes risk scoring model.Finally,nomogram was constructed by combining clinical-pathological factors of patients and mitochondrial scoring models to estimate the prognosis of gastric cancer patients.RESULT:The transcriptome data of gastric cancer patients were collected from mitochondria and senescence genes and analyzed for different expression.Finally,27 core genes were obtained.GO enrichment analysis showed that core genes were mainly distributed in the mitochondrial matrix,related to biological processes such as leukocyte migration,and related to molecular functions such as chemokine activity.The KEGG enrichment analysis results indicate that the core genes are mainly associated with NF-κB pathway.GSEA enrichment analysis identified 16 gene gets,including folate and one carbon unit metabolism.Univariate Cox regression analysis identified 10 prognostic related core genes,which were simplified by the Lasso method and ultimately included 7 genes to construct a mitochondrial—senescence gene risk scoring model.The accuracy of the model in predicting the prognosis of gastric cancer patients for 1,3,and 5 years was 0.641,0.650,and 0.604,respectively.We combined the model and gastric cancer patients clinicalpathological factors and included them in univariate and multivariate Cox regression analysis.Age(P<0.001)and risk score(P<0.001)could independently predict patient prognosis.Furthermore,it was found that patients younger than 65 years old had a higher risk score(P<0.001),and tumors with higher tumor grades had a higher risk score(P<0.001).For Phase Ⅲ,male gastric cancer patients with T stage in T3 and T4,N stage in N2 and N3,and all tumor grades have a good predictive effect(P<0.05).The nomogram constructed by age and risk score can predict the survival probability of patients at 1,3,and 5 years,especially for the 1-year survival prediction ability of patients.Conclusion:This study successfully constructed a mitochondrial-senescence gene risk scoring model consisting of seven genes:ABHD11,HSPD1,MTHFD2,TWNK,MTFR2,IGFBP6 and CXCL12.This model is more suitable for stage Ⅲ,T3,T4,N2,N3,all age,all tumor grades of male gastric cancer patients,and can effectively predict the 1,3,and 5-year survival of gastric cancer patients. |
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