The Correlation Between TLR4,HIF-1α And Inflammatory Indexes And The Clinicopathological Factors Of Cervical Cancer And The Efficacy Of Chemoradiotherapy

Objective : To investigate the correlation between the expression levels of TLR4 and HIF-1α in cervical cancer tissues and peripheral blood and the clinicopathological factors and efficacy of chemoradiotherapy in cervical cancer,and the correlation between the dynamic changes of TLR4,HIF-1α and inflammatory indexes in peripheral blood of cervical cancer and the efficacy of chemoradiotherapy,so as to provide a basis for predicting the efficacy of chemoradiotherapy in cervical cancer.Methods:1.The clinical data of patients with locally advanced cervical cancer who were pathologically confirmed and undertaken concurrent chemoradiotherapy(CCRT)in the Second Hospital of Lanzhou University from January 2019 to January 2023 were collected,including 62 cases of pre-treatment pathological tissue samples and 27 peripheral blood samples,and the expression levels of TLR4 and HIF-1α were detected by immunohistochemical staining(IHC)and enzyme-linked immunosorbent assay(ELISA),and their correlation with clinicopathological factors and the efficacy of chemoradiotherapy was analyzed.2.Peripheral blood specimens were collected before,during and after CCRT,and the dynamic changes of TLR4,HIF-1α and inflammatory indexes(IL-6,IL-8,LMR,NAR,SIRI,etc.)levels during CCRT(<1 week before CCRT;the third weekend during CCRT;<1 weeks After CCRT),and then analyzed its correlation with the sensitivity of chemoradiotherapy for cervical cancer.Results:1.The expression of TLR4 and HIF-1α in cervical cancer tissues before CCRT was significantly correlated with the FIGO stage of locally advanced cervical cancer(P<0.05),while the expression of TLR4 and HIF-1α in cervical cancer tissues was significantly correlated with age(P<0.05)and T stage(P<0.05),respectively.The expression levels of TLR4 and HIF-1α in peripheral blood were significantly correlated with FIGO stage and T stage(P<0.05)before CCRT,while the expression of TLR4 and HIF-1α in cervical cancer tissue and peripheral blood were not correlated with lymphoid metastasis,histological type and recurrence/metastasis of cervical cancer(P>0.05).2.There was a significant positive correlation between TLR4 expression and HIF-1α expression in cervical cancer tissue and peripheral blood(r=0.557,P<0.001;r=0.8702,P<0.001,respectively),and there was a correlation between peripheral blood TLR4 and squamous cell carcinoma antigen(SCC)(r=0.595,P=0.007).3.Logistic univariate analysis showed that FIGO stage,T stage,HIF-1α and SCC were the key factors affecting the efficacy of CCRT in cervical cancer,while multivariate analysis showed that FIGO stage and HIF-1α were key factors affecting the efficacy of CCRT(P<0.05),and there was no significant difference in TLR4 expression between complete response(CR)and partial response(PR)groups(P>0.05).4.Compared with pre-CCRT,the levels of TLR4,HIF-1α and NLR,PLR,SII,FAR,SIRI increased significantly(P<0.05),while the levels of APAR,LMR,NWR,NAR and PAR reduced significantly(P<0.05)at the third weekend during CCRT.After CCRT,the levels of NLR,SII,PLR and SIRI in peripheral blood increased significantly(P<0.05),while LMR,NWR,NAR and PAR decreased significantly(P<0.05).5.Based on the ROC curves of differential peripheral blood indexes between CR group and PR group after CCRT,HIF-1α,LMR,SIRI and NAR before CCRT could predict the efficacy of chemoradiotherapy for cervical cancer,and HIF-1α<0.338ng/ml,LMR≥5.302,SIRI ≤0.8 and NAR≤0.093 had the best predictive performance for CCRT efficacy.Compared with pre-CCRT,patients with a LMR decrease of less than 0.427 times and a HIF-1α increase of no more than 2.38 times were more sensitive to chemoradiotherapy at the third weekend during CCRT,while Patients with a decrease in LMR below 0.489 times had a better response to chemoradiotherapy after CCRT.Conclusions:1.The expression of TLR4 and HIF-1α in tumor tissue and peripheral blood before concurrent chemoradiotherapy for cervical cancer was significantly correlated with FIGO stage of locally advanced cervical cancer,and TLR4 was positively correlated with HIF-1α expression.2.HIF-1α,LMR,SIRI and NAR levels in peripheral blood before concurrent chemoradiotherapy for cervical cancer predicted the efficacy of chemoradiotherapy.3.The dynamic changes of LMR and HIF-1α in peripheral blood during concurrent chemoradiotherapy can predict the efficacy of chemoradiotherapy for cervical cancer.