Proteomic insights in the chemo-radiation therapy resistant cervical cancer patients

Cervical cancer continues to be a significant cause of morbidity and mortality in our patients as most of these patients present in a locally advanced stage. Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer and survival of these patients strongly depends on how the disease responds to treatment. Heterogenous treatment response and resistance occur due to multifactorial events and targeting key molecules involved in treatment resistance could combat treatment resistance. Herein, we profiled global proteomic landscape of the concurrent chemotherapy resistant cervical cancer to identify potential predictive biomarkers. Mass spectrometry based global proteomic was used to identify proteomic signature in chemoradiation resistance. The biopsy tissue samples were collected before the start of the therapy and the protein was extracted, digested from each sample and labelled with 10 plex TMT. The pooled peptides were fractionated by basic pH liquid chromatography analyzed on Orbitrap-Fusion-Tribrid mass spectrometer. Analysis of protein expression led to the identification of dysregulated protein expression between treatment sensitive and resistant patient cohorts. The proteins such as SERPINB7, STX3, LBP, EMILIN2, NQO2 and GPR180 were top five highly expressed proteins and GSTM1, ARPP19, CLCA2, GSDMB and MPC2 exhibited low expression in non-responders. Further analysis and validation experiment revealed the potential of differentially expressed protein syntaxin 3 (STX3) as a predictive biomarker for treatment resistance. We have identified an accurate and reliable biomarker STX3 to predict CCRT resistance in cervical cancer. This discovery will enable the treating oncologist to choose an alternative therapy early which might lead to an increase in the chance of survival in these patients. (author)