Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma.
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.
Matta
Ajay
A
Department of Chemistry, York University, Toronto, Ontario, Canada.
Tripathi
Satyendra Chandra
SC
DeSouza
Leroi V
LV
Grigull
Jörg
J
Kaur
Jatinder
J
Chauhan
Shyam Singh
SS
Srivastava
Anurag
A
Thakar
Alok
A
Shukla
Nootan Kumar
NK
Duggal
Ritu
R
DattaGupta
Siddhartha
S
Ralhan
Ranju
R
Michael Siu
K W
KW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D007124:Immunoenzyme Techniques; D007972:Leukoplakia, Oral / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human