title: Prediction of recurrence-free survival using a protein expression-based risk classifier for head and neck cancer.
abstract: Loco-regional recurrence in 50% of oral squamous cell carcinoma (OSCC) patients poses major challenge for oncologists. Lack of biomarkers that can predict disease aggressiveness and recurrence risk makes the scenario more dismal. On the basis of our earlier global proteomic analyses we identified five differentially expressed proteins in OSCC. This study aimed to develop protein biomarkers-based prognostic risk prediction model for OSCC. Sub-cellular expression of five proteins, S100A7, heterogeneous nuclear ribonucleoproteinK (hnRNPK), prothymosin α (PTMA), 14-3-3ζ and 14-3-3σ was analyzed by immunohistochemistry in test set (282 Indian OSCCs and 209 normal tissues), correlated with clinic-pathological parameters and clinical outcome over 12 years to develop a risk model for prediction of recurrence-free survival. This risk classifier was externally validated in 135 Canadian OSCC and 96 normal tissues. Biomarker signature score based on PTMA, S100A7 and hnRNPK was associated with recurrence free survival of OSCC patients (hazard ratio=1.11; 95% confidence interval 1.08, 1.13, P<0.001, optimism-corrected c-statistic=0.69) independent of clinical parameters. Biomarker signature score stratified OSCC patients into high- and low-risk groups with significant difference for disease recurrence. The high-risk group had median survival 14 months, and 3-year survival rate of 30%, whereas low-risk group survival probability did not reach 50%, and had 3-year survival rate of 71%. As a powerful predictor of 3-year recurrence-free survival in OSCC patients, the newly developed biomarkers panel risk classifier will facilitate patient counseling for personalized treatment.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S S
authors.initials: SS
authors.lastname: Chauhan
authors.affiliation: 1] Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India [2] Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Matta
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Srivastava
authors.affiliation: 1] Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada [2] Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Alyass
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Assi
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada [2] Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Leong
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: MacMillan
authors.affiliation: 1] Department of Otolaryngology - Head and Neck Surgery, Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada [2] Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Witterick
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada [2] Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: T J
authors.initials: TJ
authors.lastname: Colgan
authors.affiliation: Department of Surgery, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: N K
authors.initials: NK
authors.lastname: Shukla
authors.affiliation: Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: A
authors.initials: A
authors.lastname: Thakar
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M C
authors.initials: MC
authors.lastname: Sharma
authors.affiliation: Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.
authors.forename: K W M
authors.initials: KW
authors.lastname: Siu
authors.affiliation: 1] Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada [2] Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada [3] Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada [4] Department of Otolaryngology - Head and Neck Surgery, Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada [5] Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada [6] Endocrine Division, Department of Medicine, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
authors.forename: P G
authors.initials: PG
authors.lastname: Walfish
authors.affiliation: 1] Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada [2] Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada [3] Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada [4] Department of Otolaryngology - Head and Neck Surgery, Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada [5] Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Ralhan