31P - Identification of proteins associated with mRNA processing and maturation by quantitative proteomic analysis in Indian cervical cancer patients

Background

Cervical cancer is a major public health concern as it is the fourth leading cause of cancer-related fatalities among women. India has the highest incidence of cervical cancer worldwide. Omics diagnostic tools, particularly proteomics, are helpful in tracking the development of the disease as cancer therapy continues to shift towards precision medicine. The primary objective of this study was to explore the global protein expression patterns of cervical cancer in the Indian population for the first time to encourage the application of current diagnostic and treatment modalities.

Methods

We employed MS-based quantitative global (Label-free quantification or LFQ) and targeted proteomics (multiple reaction monitoring or MRM) in bio-banked tissue samples of cervical cancer and healthy tissue (Control=8, Tumor=7; 6 Paired, 2 unpaired). With a very small amount of starting tissue material (10-12 mg) proteomic biomarker profiling was conducted as pilot research. Finally, a complex set of protein candidates belonging to the mRNA splicing and MTORC1 signaling pathway has been confirmed and refined at the peptide level by MRM assay.

Results

We observed proteins belonging to the mRNA processing and maturation via alternative splicing pathway were overexpressed in cervical tumors. Heterogeneous nuclear ribonucleoproteins (hnRNPs), the components of spliceosome complex regulate both constitutive and alternative splicing in tumors. We found at least 5 hnRNPs and few HSP (heat-shock proteins) to be significantly overexpressed in tumors via global proteomics. Validation of candidate hnRNPs (HNRNPA2, HNRNPA1) and Heat-shock proteins (HSPs) were done by targeted proteomics. Furthermore, we developed a comprehensive panel of peptides which can be investigated to check for the effectiveness of tumour development which pave the way towards a better diagnosis.

Conclusions

This foundation study, for the very first time, facilitated the development of a panel of proteomic biomarkers of Cervical cancer in Indian population. We propose that a set of these markers including HNRNPs can be further useful for the development of a complete biomarker panel for cervical cancer diagnosis.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Indian Institute of Technology, Bombay.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.