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Prediction of recurrence free survival for esophageal cancer patients using a protein signature based risk model

Raghibul Hasan, Gunjan Srivastava, Akram Alyass, Rinu Sharma, Anoop Saraya, Tushar K. Chattopadhyay, Siddartha DattaGupta, Paul G. Walfish, Shyam S. Chauhan _ and Ranju Ralhan _

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Oncotarget. 2022; 13:1020-1032. https://doi.org/10.18632/oncotarget.10656

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Abstract

Raghibul Hasan1, Gunjan Srivastava2, Akram Alyass2,3, Rinu Sharma4, Anoop Saraya5, Tushar K. Chattopadhyay6, Siddartha DattaGupta7, Paul G. Walfish2,8,9,10, Shyam S. Chauhan1 and Ranju Ralhan1,2,9,10,11

1 Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

2 Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

3 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

4 University School of Biotechnology, Guru Gobind Singh Indraprastha Univesity, Dwarka, New Delhi, India

5 Department of Gastroenterology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

6 Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

7 Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

8 Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada

9 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

10 Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada

11 Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada

Correspondence to:

Ranju Ralhan, email: rralhan@mtsinai.on.ca
Shyam S. Chauhan, email: s_s_chauhan@hotmail.com

Keywords: esophageal cancer; wnt proteins; dishevelled; molecular markers; prognosis

Received: January 15, 2016     Accepted: May 16, 2016     Published: September 14, 2022

Copyright: © 2022 Hasan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Background: Biomarkers to predict the risk of disease recurrence in Esophageal squamous cell carcinoma (ESCC) patients are urgently needed to improve treatment. We developed proteins expression-based risk model to predict recurrence free survival for ESCC patients.

Methods: Alterations in Wnt pathway components expression and subcellular localization were analyzed by immunohistochemistry in 80 ESCCs, 61 esophageal dysplastic and 47 normal tissues; correlated with clinicopathological parameters and clinical outcome over 86 months by survival analysis. Significant prognostic factors were identified by multivariable Cox regression analysis.

Results: Biomarker signature score based on cytoplasmic β-catenin, nuclear c-Myc, nuclear DVL and membrane α-catenin was associated with recurrence free survival [Hazard ratio = 1.11 (95% CI = 1.05, 1.17), p < 0.001, C-index = 0.68] and added significant prognostic value over clinical parameters (p < 0.001). The inclusion of Slug further improved prognostic utility (p < 0.001, C-index = 0.71). Biomarker Signature Scoreslug improved risk classification abilities for clinical outcomes at 3 years, accurately predicting recurrence in 79% patients in 1 year and 97% in 3 years in high risk group; 73% patients within low risk group did not have recurrence in 1 year, with AUC of 0.76.

Conclusions: Our comprehensive risk model predictive for recurrence allowed us to determine the robustness of our biomarker panel in stratification of ESCC patients at high or low risk of disease recurrence; high risk patients are stratified for more rigorous personalized treatment while the low risk patients may be spared from harmful side effects of toxic therapy.


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