Immune Checkpoint Molecular Expression And Prognostic Analysis Of IgG4-associated In Biliary Pancreatic Malignancies

Objective: To investigate the correlation between serum IgG4 level and immune checkpoint molecular expression in tumor tissue and prognosis in patients with biliary pancreatic cancer.Methods: Data of patients diagnosed with biliary pancreatic system malignant tumor by postoperative histopathology after surgery in Affiliated Hospital of Qingdao University from January 1,2016 to December 31,2020 were retrospectively analyzed.Patients were grouped according to serum IgG4 levels,among which serum IgG4 level≥1.35g/L(63 cases)was classified as elevated IgG4 group,serum IgG4 level<1.35g/L(63 cases)was classified as normal IgG4 group.General data,operation-related data,postoperative conditions,and pathological data of the two groups of patients were compared for prognosis and survival analysis.Results: There were 126 patients in the two groups,including 100 males and 26 females,and there was no statistical difference in gender(P > 0.05).The median age of patients in the serum IgG4 increased group was 63 years old,and the median age of patients in the serum IgG4 normal group was 66 years old,with no statistical difference(P > 0.05).There was no significant difference in other general data including body mass index(BMI),main symptoms,diabetes history,fasting blood glucose,preoperative CA199 level,preoperative CA125 level,preoperative CEA level,preoperative CA242 level(P > 0.05).In the elevated IgG4 group,47 patients received radical surgery and 16 patients received palliative surgery,while in the normal IgG4 group,49 patients received radical surgery and 14 patients received palliative surgery.There was no statistically significant difference in surgical methods between the two groups(P>0.05).In terms of operation time,the median operation time of serum IgG4 increased group and normal group was 305.0min and 311.0min,respectively,with no statistical significance(P > 0.05).There was no significant difference in intraoperative blood loss and intraoperative blood transfusion between the two groups(P>0.05).There was no statistical significance in the incidence of postoperative complications and postoperative blood glucose level between the elevated serum IgG4 group and the normal group(P > 0.05).There was no statistical significance between the two groups in whether or not patients received adjuvant therapy after surgery and the way of receiving adjuvant therapy(P > 0.05).There were no significant differences in tumor histological type,tumor differentiation degree,tumor diameter,Ki-67 index,vascular thrombi,nerve invasion,lymph node metastasis,and PD-L1(22C3)CPS score between the two groups(P > 0.05).There was a statistically significant difference in PD-L1 CPS score between the elevated serum IgG4 group and the normal serum IgG4 group in patients with pancreatic malignancies(P < 0.05).There was no significant difference in PD-L1 CPS score between the elevated serum IgG4 group and the normal serum IgG4 group in patients with biliary tract malignant tumor(P > 0.05).All patients were followed up for 23 to 82 months,with a median follow-up time of 37 months.The median survival time was 29 months in the group with normal serum IgG4 and 18 months in the group with elevated serum IgG4,and the difference was statistically significant by Log-Rank test(P < 0.05).Serum IgG4 level(HR=2.733,95%CI: 1.658-4.504)and tumor site(HR=2.494,95%CI: 1.443-4.311)were independent factors influencing poor prognosis in patients with biliary pancreatic malignancy.Conclusions: Pancreatic malignant tumor patients with elevated serum IgG4 have worse prognosis than those with normal serum IgG4.The predictive value of serum IgG4 level for prognosis of biliary malignant tumor is not clear,and larger sample size data is needed for research.The expression of PD-L1 was higher in pancreatic cancer patients with increased serum IgG4 levels,while the expression of PD-L1 was not different in biliary cancer patients with different serum IgG4 levels.It was speculated that pancreatic cancer patients with increased serum IgG4 levels might have a more obvious response to immune checkpoint inhibitors.