Primary Liver Cancer: A Retrospective Study Of 521 Patients And Research Of Molecular Mechanism Of LIGHT

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Analysis research on anatomic hepatectomy of primary liver cancer Background and aims:Patient's preoperative liver function and cirrhosis have effects on surgical decisions and the long-term prognosis.Since the concept of anatomic hepatectomy been put forward,it had been under extensive attention and controversy.Up to now,there are plenty of researches on the difference of long-term prognosis after anatomic and non-anatomic hepatectomy.However,it's still controversial about which surgical decisions to make under different patients' condition.And the effect of anatomic hepatectomy on perioperative outcomes,including hemorrhage during operation and postoperative complications is also controversial,especially in those patients with cirrhosis.Therefore,in this research,we focused on making a retrospective and descriptive analysis on patients with primary liver cancer in our center,by selecting patients meeting the inclusion criteria,and making a retrospective analysis on patients receiving anatomic and non-anatomic hepatectomy,then we explored the possible risk factors of anatomic hepatectomy.We aimed at providing a preliminary result of descriptive analysis and evaluation based on data of primary liver cancer surgery in our center.Methods:In this research,we selected the general information,laboratory test results,surgical information and pathologic results of 521 patients with primary liver cancer after surgery in our center during January 2013 to December 2018.Based on the methods of resection,we divided all the patients to group receiving anatomic hepatectomy(197 cases)and group receiving non-anatomic hepatectomy(324 cases).Firstly,we selected the preoperative information of each group to make a descriptive analysis,then we explored the independent risk factors of anatomic hepatectomy using univariate and multivariate logistic regression analysis.Secondly,we compared the perioperative outcomes of two groups,and made subgroup analysis based on certain conditions.All the statistic data were analyzed using software SPSS.22.0,and P<0.05 represented a significant difference.Results:Univariate and multivariate logistic analysis showed that compared to non-anatomic hepatectomy,the independent risk factors of anatomic hepatectomy included PTA(OR=1.023,95%CI:1.007-1.040,P=0.004),CA199(OR=1.000,95%CI:1.000-1.001,P=0.032),tumor size(OR=1.166,95%CI:1.086-1.252,P<0.001),and PVTT(OR=2.169,95%CI:1.156-4.070,P<0.001).And age(OR=0.967,95%CI:0.946-0.990,P=0.004)was the only protective factor of anatomic hepatectomy in this research.Analysis of perioperative outcomes showed that compared to non-anatomic hepatectomy,anatomic hepatectomy caused more intraoperative blood loss,longer operation duration,more feasibility to enter ICU after surgery,more observation time in ICU and more hospitalization expenses.For subgroup analysis,only in group of patients with cirrhosis,it's shown that anatomic hepatectomy causes more intraoperative blood loss,longer operation duration,more feasibility to enter ICU after surgery,more observation time in ICU,more hospitalization expenses and longer postoperative abdominal drainage time.Conclusion:Two groups of patients separately receiving anatomic hepatectomy and non-anatomic hepatectomy had significant difference in age,biliary indicators like ALP,tumor markers like CA199,tumor size,PVTT,and Child grade.For patients with cirrhosis,anatomic hepatectomy may cause worse perioperative outcomes,therefore,it's necessary to consider the preoperative condition of patient and avoid anatomic hepatectomy as possible.Part ? Survival and prognosis analysis of preoperative indicators on primary liver cancerBackground and aims:The prognosis of primary liver cancer after surgery is still not satisfactory,and the 5 years overall survival rate predicted to be around 50%,and the recurrence rate at fifth year reached 70%.Therefore,it's meaningful to find factors that may influence the formation and metastasis of liver cancer,and explore the prediction potential for long-term prognosis of these factors.It's significant to explore prediction factors of liver cancer prognosis in preoperative indicators,especially in tumor associated inflammation indicators.In this research,we selected the preoperaive indicators of patients with primary liver cancer receiving surgery,and aimed to make a survival and prognosis analysis and find the independent prediction factors.Methods:We selected the preoperative indicators and the follow-up information of 170 patients with primary liver cancer receiving surgery during January 2013 and December 2014 in our center,and explored the effect of preoperative indicators on long-term survival outcomes including overall survival and recurrence free survival of patients,by univariate and multivariate Cox regression analysis.Then we compared the effect of preoperative inflammation model including Neutrophil to Lymphocyte ratio(NLR),Lymphocyte to monocyte ratio(LMR)and Prognostic nutritional index(PNI)on long-term survival,and drew Kaplan-Meier survival curves of different preoperative and inflammation model on long-term prognosis,and selected the independent prediction factors for outcome events.All the statistic data were analyzed using software SPSS.22.0,and P<0.05 represented a significant difference.Results:Univariate and multivariate Cox regression analysis on single preoperative indicators showed,for the overall survival prognosis of patients with primary liver cancer,AFU(HR=1.022,95%CI:1.009-1.036,P=0.001)and tumor size(HR=2.123,95%CI:1.172-3.848,P=0.013)were risk factors for outcome event.And for recurrence free survival prognosis,AFU(HR=1.034,95%CI: 1.020-1.047,P<0.001)and intrahepatic spread(HR=1.860,95%CI:1.105-3.132,P=0.020)were risk factors,and PT(HR=0.948,95%CI:0.910-0.987,P=0.010)was a protective factor for the outcome event.Besides,compared to group with lower AFU(?35U/L),group with higher AFU(>35U/L)had a worse prognosis on both long-term overall survival(P<0.001)and recurrence free survival(P=0.003).Among the preoperative inflammation models,the LMR model had certain prediction potential for the prognosis(HR=0.593,95%CI:0.353-0.996,P=0.048)on recurrence free survival for patients with primary liver cancer.Patients with higher LMR had a better prognosis on recurrence free survival.Conclusion:Among all the preoperative indicators,AFU had possible prediction potential for the prognosis on both overall survival and recurrence free survival for patients with primary liver cancer,and patients with higher AFU(>35U/L)may had worse long-term prognosis.Among the preoperative inflammation models,the LMR model had possible prediction potential for the prognosis on recurrence free survival for patients with primary liver cancer.Part ? Research on inhibition of LM3 cell line proliferation by LIGHT through inducing cell apoptosisBackground and aims:T lymphocyte is one of the immune cells in tumor microenvironment and the major cell to exert the tumor-killing effect.LIGHT is the homologous molecule of lymphotoxin-?,and is commonly expressed on immune cells like T cells and NK cells.LIGHT may play a role of anti-tumor effect in tumor microenvironment,majorly through its receptor,LT?R,in a direct or indirect way.Up to now,there are few researches on the relationship between LIGHT and liver cancer,and there is potential value to explore the effect of LIGHT on immune elimination of liver cancer cells.Methods:We firstly compared the difference in expression of LIGHT between liver cancer tissues and adjacent tissues using bioinformatics method.Then we transfected LM3 cell lines with lentivirus for overexpression of LIGHT,and verified its expression using PCR and immue fluorescence.Then we explored the effect of LIGHT on proliferation of LM3 cell by CCK8 and colony-formation experiment.Then we explored the effect of LIGHT on apoptosis and cell cycle of LM3 cell using flow cytometry.Possible pathways and mechanisms were explored by Western-blot.All the statistic data were analyzed using software SPSS.22.0,and P<0.05 represented a significant difference.Results:The expression of LIGHT was lower in liver cancer tissues than in adjacent tissues.Among different liver cancer cell lines,LM3 cell had a relatively high expression of LT?R and low expression of HVEM.The results of PCR and immune fluorescence verified the overexpression of LIGHT in LM3 cell line.Overexpression of LIGHT in LM3 cells significantly inhibited its proliferation,and induced cell apoptosis but had no significant effect on cell cycle of LM3 cells.Further exploration on the potential mechanisms showed that LIGHT may influenced the non-classical NF-?B pathways in LM3 cells,and may contributed the apoptosis of LM3 cells by activating exogenous apoptotic signaling pathways through the Erk pathway?Conclusion:The expression of LIGHT was lower in liver cancer tissues than in adjacent tissues.Overexpression of LIGHT in LM3 cells may influenced the non-classical NF-?B pathways and significantly inhibited its proliferation possibly by inducing cell apoptosis.