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Serum levels of HMGB1 might have a predictive role for neoadjuvant radiotherapy combined with chemotherapy in rectal cancer patients
Background
The standard treatment for locally advanced rectal cancer (LARC), is neoadjuvant concurrent chemoradiation (nCCRT), after which total mesorectal excision is performed. The degree of response to combined therapy varies in patients. Tumor repopulation during radiotherapy is an important cause of treatment failure. High mobility group box 1 (HMGB1) is a nuclear protein released during the course of radiotherapy. It is essential for normal cellular function but also regulates the proliferation and migration of tumor cells. HMGB1 is a biomarker for necrotic cell death and its secretion appears to be important in cancer progression. The aim of our study was to evaluate the serum level of HMGB1 in patients with LARC before the start and at the end of the course of nCCRT as well to investigate its correlation with patient`s clinicopathologic characteristics and response rate.
Methods
Patients with adenocarcinoma LARC (n=65) stage II and III were investigated between 2015 and 2021. The cohort included 24 men (37%) and 41 women (63%) with a mean age of 63±10.6 years. All patients were treated with nCCRT (using 45–50.4 Gy in 25–28 fractions) with Capecitabine. The tumor objective response rate (ORR), is the proportion of patients who have a partial or complete response to the treatment. HMGB1 serum levels before and after nCCRT were measured by commercial ELISA kit.
Results
ORR was 52.3%. Serum HMGB1 levels before and after nCCRT course did not correlate with clinical and pathological T and N stages of the patients. Wilcoxon test showed that patients after the nCCRT has significantly higher HMGB1 values than patients before the treatment (9.94 ± 4.60 vs 6.61 ± 2.25, p < 0.0001). Patients who response to treatment had significantly lower serum HMGB1 levels than those who did not response (8.79 ± 4.16 vs 11.21 ± 4.80, p=0.030). ROC analyses revealed that, at the optimal cut-off values for HMGB1 after treatment, the biomarker could significantly and easily distinguish between patients with or without response to nCCRT (AUC=0.657, 95% CI: 0.524–0.790, p=0.034) with a sensitivity of 74% and a specificity of 50%. The increased serum concentration of HMGB1 after treatment could potentially served as negative predictor of poor response to radiotherapy (AUC=0.727, 95% CI: 0.603–0.851, p=0.02) with sensitivity of 77.4% and specificity of 56.9%. Moreover, multiple binary logistic regression analysis showed that higher concentration levels ofHMGB1 after nCCRT are associated with a poor response to therapy (OR=1.129, 95% CI: 1.006-1.267, p=0.039).
Conclusions
Our results indicate that serum levels of HMGB1 after nCCRT and their dynamics might be a potential predictive marker of poor response to nCCRT.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
