Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma
Ajay Matta
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
The first two authors contributed equally to this study.
Search for more papers by this authorSatyendra Chandra Tripathi
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
The first two authors contributed equally to this study.
Search for more papers by this authorLeroi V. DeSouza
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
Search for more papers by this authorJörg Grigull
Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada
Search for more papers by this authorJatinder Kaur
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorShyam Singh Chauhan
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAnurag Srivastava
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAlok Thakar
Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorNootan Kumar Shukla
Department of Surgery, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorRitu Duggal
Department of Dental Surgery, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorSiddhartha DattaGupta
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorCorresponding Author
Ranju Ralhan
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada
RR and KWMS are senior authors in this study.
Fax: +(416)736-5936.
Centre for Research in Mass Spectrometry, Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3Search for more papers by this authorK.W. Michael Siu
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
RR and KWMS are senior authors in this study.
Search for more papers by this authorAjay Matta
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
The first two authors contributed equally to this study.
Search for more papers by this authorSatyendra Chandra Tripathi
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
The first two authors contributed equally to this study.
Search for more papers by this authorLeroi V. DeSouza
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
Search for more papers by this authorJörg Grigull
Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada
Search for more papers by this authorJatinder Kaur
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorShyam Singh Chauhan
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAnurag Srivastava
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorAlok Thakar
Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorNootan Kumar Shukla
Department of Surgery, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorRitu Duggal
Department of Dental Surgery, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorSiddhartha DattaGupta
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
Search for more papers by this authorCorresponding Author
Ranju Ralhan
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada
RR and KWMS are senior authors in this study.
Fax: +(416)736-5936.
Centre for Research in Mass Spectrometry, Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3Search for more papers by this authorK.W. Michael Siu
Department of Chemistry, York University, Toronto, Ontario, Canada
Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada
RR and KWMS are senior authors in this study.
Search for more papers by this authorFax: +(416)736-5936.
Abstract
Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography–mass spectrometry showed overexpression of heterogeneous ribonucleoprotein K (hnRNP K), a transformation-related RNA-binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head-and-neck/oral squamous cell carcinomas (HNOSCCs). Immunohistochemical analysis of hnRNP K was performed in 100 HNOSCCs, 199 leukoplakias and 55 nonmalignant tissues and correlated with clinicopathologic parameters and disease prognosis over 6 years for HNOSCCs. hnRNP K nuclear expression increased from normal tissues to leukoplakia, and frank malignancy (p < 0.001). Cytoplasmic hnRNP K increased significantly from leukoplakia to HNOSCCs (p < 0.001) and was associated with poor prognosis of HNOSCCs (p = 0.011) by Kaplan–Meier analysis. The most important finding of our follow-up study is that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, whereas its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis, suggesting its putative utility in clinical management of HNOSCC. © 2009 UICC
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