Affinity proteomics led identification of vimentin as a potential biomarker in colon cancers: insights from serological screening and computational modelling

Abstract

Proteomic analysis using multiplex affinity reagents is perhaps the most reliable strategy to capture differentially expressed proteins that are slightly or immensely modified. In addition to expressional variation, it is comprehensively evident that the immunogenicity of a protein can be a deciding factor for instigating an inflammation afflicted-carcinogenesis. Considering both these factors, a simple and systematic strategy was designed to capture the immunogenic cancer biomarkers from sera of colorectal cancer patients. The affinity reagent, in the form of an antibody repertoire against the secretome of the HT29 cell line was used to grade the sera samples on the basis of the degree of immuno-reactivity and to capture differentially expressed antigens from the patient sera. Following affinity based 2DE-MALDI-TOF; the proteins were identified as (1) soluble vimentin; and (2) TGF-beta-inhibited membrane-associated protein (PP16B), in colon cancer sera and (3) keratin, type II cytoskeletal protein in rectal cancer sera. Pathway reconstruction and protein-protein networking of identified proteins predicted only Vimentin to be physically and genetically engaged in close proximity with the most established colorectal cancer associated tumorigenic pathways. Furthermore, our findings suggest that a possible surface stoichiometric shift in the structure of protein could be due to mutations in the coding sequence of Vimentin that may elicit its enhanced secretion possibly due to protein-hyperphosphorylation. Of the three proteins identified, only Vimentin showed higher expression in sera of colon cancer patients alone. Thus, it could be argued that vimentin might help in predicting individuals at higher risk of developing colon cancers. Our data are therefore suggestive of using vimentin as an antigen for tumor vaccination in an autologous set-up for colon cancers.

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients

“…Vimentin is a canonical marker of EMT, and a novel study based on computational modeling recently proposed vimentin as a promising biomarker for CRC [24]. We conducted a retrospective study to validate its clinical significance in patients with stage II CRC.…”

Translational Research and Plasma Proteomic in Cancer

“…Vimentin [Bukhari et al, 2015];N-cadherin [Yan et al, 2015b]; GRObeta [Zheng et al, 2015]; GATA5 and SFRP2 [Zhang et al, 2015c]; kinesin 26B [Wang et al, 2015b]; microRNA-155 ; KRAS [Bruera et al, 2015] Lung cancer Tyrosine kinase-3 [Zhang et al, 2015a]; Annexin A2 [Yang et al, 2015]; osteopontin [Yan et al, 2015a]; SOX4 [Wang et al, 2015a]; GM2-activator protein [Potprommanee et al, 2015]; IL1A [Li et al, 2015b]; alpha-actinin 4 [Wang et al, 2015c] cancer [Brichory et al, 2001]. Humoral immune response against tumor antigens in cancer patients have been used in a serum-based assays to monitor the disease progression or in the development of anticancer vaccines [GuhaThakurta et al, 2015].…”

Molecular dynamics simulation analysis of the effect of T790M mutation on epidermal growth factor receptor protein architecture in non-small cell lung carcinoma

“…Atomic insight into altered architecture due to mutations using molecular dynamic simulation (MDS) is a practice currently in use (15,16). The present study used MDS to investigate the anomalies in the gatekeeper region due to mutation from threonine to methionine.…”