Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach

Neetu  Rawal; Gururao  Hariprasad; Sabyasachi  Bandyopadhyay; Nihar  Ranjan Dash; Sunil  Kumar; Prasenjit  Das; Sharmistha  Dey; Maroof  Ahmad Khan; Amar  Ranjan; Anita  Chopra; Sundeep  Saluja; Showket  Hussain; G.K.  Rath; Tanvir Kaur; Pranay Tanwar

doi:10.17305/bb.2024.10704

Authors

Neetu Rawal Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India https://orcid.org/0000-0003-4930-0250
Gururao Hariprasad Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
Sabyasachi Bandyopadhyay Proteomics Laboratory, Centralized Core Research Facility, All India Institute of Medical Sciences, New Delhi, India
Nihar Ranjan Dash Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India
Sunil Kumar Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
Prasenjit Das Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Sharmistha Dey Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India
Maroof Ahmad Khan Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India https://orcid.org/0000-0001-9449-6518
Amar Ranjan Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Anita Chopra Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Sundeep Saluja Department of Gastrointestinal Surgery, Govind Ballabh Pant Hospital, New Delhi, India
Showket Hussain Division of Molecular Oncology, National Institute of Cancer Prevention and Research, Indian Council of Medical Research, New Delhi, India
G.K. Rath Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Tanvir Kaur Division of Non-Communicable Diseases, Indian Council of Medical Research, New Delhi, India
Pranay Tanwar Laboratory Oncology Unit, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India https://orcid.org/0000-0002-2357-976X

DOI:

https://doi.org/10.17305/bb.2024.10704

Keywords:

Liquid chromatography assisted tandem mass spectrometry (LC-MS/MS), biomarker, differentially expressed proteins (DEPs), gallbladder cancer (GBC), enzyme-linked immunosorbent assay (ELISA), real time-polymerase chain reaction (RT-PCR), inflammatory lesion

Abstract

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates. Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan–Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables. Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.