Dataset Information

Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer

ABSTRACT: Tongue squamous cell carcinoma is characterised by poor prognosis and high metastatic events. Patients with unresectable tumors are benefiting from neoadjuvant chemotherapy (NACT) which surgical resection, and controls distant metastasis, and locoregional recurrence. However, resistance to NACT limit the success of the treatment regimen. In this study, we investigated the altered proteome and phosphoproteome of NACT resistant and sensitive cohort using Mass spectrometry-based proteomics. We carried out proteomic as well as phosphoproteomic analysis of treatment naïve tongue cancer patients whose response to NACT is recorded. Proteomic analysis revealed distinct protein expression between the responders and non-responders. The Phosphoproteomic analysis revealed kinases and the pathways associated with NACT resistance in tongue cancer.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Tongue Cancer Cell

DISEASE(S): Tongue Cancer

SUBMITTER: Irene A George

LAB HEAD: Dr. Prashant Kumar

PROVIDER: PXD037356 | Pride | 2023-03-11

REPOSITORIES: Pride

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Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer.

George Irene A IA Sathe Gajanan G Ghose Vivek V Chougule Anuradha A Chandrani Pratik P Patil Vijay V Noronha Vanita V Venkataramanan R R Limaye Sewanti S Pandey Akhilesh A Prabhash Kumar K Kumar Prashant P

Frontiers in cell and developmental biology 20221028

Tongue squamous cell carcinoma is an aggressive oral cancer with a high incidence of metastasis and poor prognosis. Most of the oral cavity cancer patients present in clinics with locally advanced unresectable tumors. Neoadjuvant treatment is beneficial for these individuals as it reduces the tumor size aiding complete resection. However, patients develop therapy resistance to the drug regimen. In this study, we explored the differential expression of proteins and altered phosphorylation in the ...[more]

PMID: 36393868

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Project description:Importance: Neoadjuvant chemoradiotherapy (CRT) is the standard of care for advanced rectal cancer. Yet, predicting response to CRT remains an unmet clinical challenge. Objective: To investigate the transcriptomic determinants to predict response to neoadjuvant CRT and survival in patients with advanced rectal cancer. Design: A single-center, retrospective, cohort study. Setting: A comprehensive cancer center. Participants: Pre-treatment biopsies from 298 patients with rectal cancer, who were later treated with neoadjuvant CRT between 2004 and 2020, were analyzed by RNA sequencing. Main measures and outcomes: Transcriptional subtyping was performed by consensus molecular subtype (CMS) classification. Immune cell infiltration was assessed using MCP-counter scores and single-sample gene set enrichment analysis (ssGSEA). Patients with surgical specimens of tumor regression grade (TRG) 3-4 or who were managed by the watch-and-wait approach for more than 3 years were defined as good responders. Results: Patients classified as CMS1 (6.4%) had a significantly higher rate of good responders; albeit survival was comparable among the four subtypes. Good responders exhibited an enrichment in various immune-related pathways (IFNg and a responses, allograft rejection, IL6 STAT3 signaling during acute phase response, and inflammation), as determined by ssGSEA. MCP-counter scores for cytotoxic lymphocytes were significantly higher for good responders than non-responders (p = 0.0003), and significantly higher for responders than non-responders in GSE109057 (p = 0.0137), GSE87211 (p = 0.0092), and GSE45404 (p = 0.0327) datasets. Cytotoxic lymphocyte MCP-counter score was thus considered an independent predictor of response to CRT, as determined in the multivariable Cox analysis (OR 3.810 [95% CI 1.820-7.970]; p = 0.0004). Multivariable Cox analysis, including post-operative pathological factors, revealed cytotoxic lymphocyte MCP-counter score to be independently associated with recurrence-free survival (HR 0.382 [95% CI 0.158-0.923]; p = 0.0325) and overall survival (HR 0.157 [95% CI 0.030-0.827]; p = 0.0290). ssGSEA showed significantly higher levels of four subpopulations of cytotoxic cells (effector memory CD8 T, natural killer T, natural killer, and activated CD8 T cells) among good responders than non-responders. Conclusions and Relevance: Cytotoxic lymphocyte score, as computed by RNA sequencing, could be a useful marker for predicting response to CRT and survival among patients with rectal cancer.

Dataset Information

Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer

Publications

Integrated proteomics and phosphoproteomics revealed druggable kinases in neoadjuvant chemotherapy resistant tongue cancer.

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