Abstract: Objective To predict the effects of preoperative serum interleukin-34 (IL-34) and matrix metalloproteinase-9 (MMP-9) levels on the clinical stage and prognosis of primary liver cancer (PLC) based on mediation effect analysis. Methods 186 patients with PLC were selected as subjects, all of whom were treated in Shanghai Health Medical College Affiliated Chongming Hospital from June 2017 to June 2021. The subjects were divided into stage I group, stage II group and stage III group according to clinical stage. The subjects were followed up after the operation. Those who died from all causes during the follow-up period were included in the poor prognosis group, and the remaining were assigned to the good prognosis group. The clinical data of the subjects were collected and the levels of serum IL-34 and MMP-9 were detected before operation. Univariate and ordered Logistic regression were used to analyze the independent factors affecting the clinical stage of patients. Univariate and multivariate Cox regression were used to analyze the independent risk factors for poor prognosis. The mediating effect was analyzed by screening out variables that affect both clinical analysis and prognosis of patients as covariables. Results Among the 186 patients included in this study, 12 patients were lost to follow up, with a loss rate of 6.45% (12/186). Among the other 174 patients, 45 patients were in stage I, 70 patients in stage II, 59 patients in stage III, and 52 patients died of all causes, with an adverse prognosis rate of 29.89% (52/174). Univariate and multivariate Logistic regression analysis showed that lymph node metastasis, tumor size (>5 cm), Barcelona Clinic Liver Cancer stage (BCLC stage C), low albumin, IL-34 and MMP-9 were all independent risk factors affecting the clinical stage progression of patients with PLC (P<0.05). Univariate and multivariate Cox regression analysis showed that lymph node metastasis, tumor size (>5 cm), BCLC stage (grade C), Child-Pugh grade (grade B), low albumin, IL-34 and MMP-9 were independent risk factors for poor prognosis in patients with PLC (P<0.05). Lymph node metastasis, tumor size, BCLC stage, and low albumin were included in the mediation effect model as covariables. The results showed that preoperative serum IL-34 and MMP-9 had a positive predictive effect on the poor prognosis of patients with primary liver cancer (β=1.853, 2.214, both P<0.001). They also had positive predictive effect on clinical stage (β=0.264, 0.478, P<0.001). After the clinical stage was included in the model, preoperative serum IL-34 and MMP-9 levels had a positive predictive effect on the poor prognosis of patients with primary liver cancer (β=2.436, 3.108, both P<0.001). Direct effect accounted for 78.45% and 82.36% respectively, indirect effect accounted for 21.55% and 17.64% respectively. Conclusion The higher the levels of serum IL-34 and MMP-9 before operation, the higher the risk of poor prognosis in patients with primary liver cancer. The higher the level of serum IL-34 and MMP-9 before operation can directly affect the prognosis of patients, and also indirectly affect the prognosis of patients through affecting the clinical stage.

Key words: Interleukin-34, Matrix metalloproteinase-9, Primary liver cancer, Clinical stage, Prognosis, Mediation analysis