Introduction/Background Cervical cancer (CaCx) is the second most common malignancy in women in India. Autophagy is one of the significant hallmarks of cancer in which high mobility group box 1 (HMGB1) plays a crucial role. Aberrant expression of HMGB1 is associated with tumor development, progression and poor prognosis. There are no reports available studying HMGB1, autophagy related molecule in context to clinical significance in cancer cervix. Thus, we aim to investigate the association between HMGB1 and its associated molecules (RAGE, p53 & p62) in CaCx. We have also evaluated the clinical significance of serum HMGB1 in CaCx diagnosis.
Methodology 50 subjects including 20 CaCx patients, 20 healthy women (controls) and 10 controls having gynecological disorder other than malignancy were recruited. Circulatory levels of HMGB1 were measured by ELISA. mRNA and protein levels of HMGB1 and its associated molecules were quantitated using Q-PCR and western blotting, respectively in tissues of patients and controls. HeLa cells were used as positive control for HMGB1. Data was statistically analyzed.
Results Circulatory levels of HMGB1 were significantly higher in patients as compared to controls. mRNA and protein expression of HMGB1 were significantly higher in tumor tissues in comparison to controls. The levels of RAGE, p53 and p62 were also significantly elevated than their expression in controls at mRNA as well as at protein levels. ROC curve analysis showed better sensitivity and specificity for HMGB1 for non-invasive diagnosis of CaCx in liquid biopsy.
Conclusion HMGB1 level could be a useful and specific marker for evaluating the disease and diagnosis in non-invasive liquid biopsy. Autophagy mediated HMGB1/RAGE pathway might play a significant role in the pathogenesis of CaCx. Validation in larger patient cohort might exploit HMGB1 as a novel non-invasive diagnostic marker for CaCx in liquid biopsy in future.
Disclosure Nothing to disclose
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