Abstract
ObjectiveLIN28B is a conserved RNA-binding protein critically involved in development, cellular metabolism and tumorigenesis. It is frequently overexpressed in human cancers and correlates with tumor aggressiveness as well as unfavorable prognosis. However, the expression pattern and oncogenic roles of LIN28B during oral squamous cell carcinoma (OSCC) development and progression has not been well established yet. Here, we sought to determine the expression of LIN28B and its clinical significance using chemical-induced OSCC animal model, cell lines and primary specimens.MethodThe OSCC animal model was induced using 7,12-dimethyl-1,2-bezan-tracene (DMBA) painting in the hamster buccal pouch. Buccal lesions from animals were obtained from different time points and subjected to routine histological analyses and immunohistochemical staining of LIN28B. The mRNA, protein abundance and subcellular localization of LIN28B was determined in a panel of OSCC cell lines by real-time RT-PCR, western blot and immunofluorescence. The expression levels of LIN28B in human primary OSCC samples were further evaluated by immunohistochemical staining. Moreover, the relationship between LIN28B and several clinicopathological parameters as well as patients’ prognosis were also assessed.ResultsOur results revealed that negative or low LIN28B expression was commonly observed in normal epithelial, whereas more LIN28B abundance was identified in epithelial dysplasia and invasive SCC in the DMBA-induced OSCC animal model. Overexpression of LIN28B was identified in a major fraction of OSCC samples(39/58) and significantly associated with tumor size (P = 0.049) and advanced clinical stages (P = 0.0286). Patients with increased LIN28B had markedly reduced overall survival as compared to those with low LIN28B. Multivariate survival analyses further indicated that LIN28B abundance served as an independent prognostic factor for patients’ overall survival.ConclusionsOur findings reveal that LIN28B is critically involved in OSCC initiation and progression and aberrantly overexpressed in human OSCC. It might represent a novel diagnostic and prognostic biomarker for oral cancer.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the common solid cancers worldwide with well-known etiologic factors including smoking abuse, alcohol consumption as well as HPV infection, etc. [1]
Our results revealed that negative or low LIN28B expression was commonly observed in normal epithelial, whereas more LIN28B abundance was identified in epithelial dysplasia and invasive SCC in the DMBA-induced OSCC animal model
Our findings reveal that LIN28B is critically involved in OSCC initiation and progression and aberrantly overexpressed in human OSCC
Summary
Oral squamous cell carcinoma (OSCC) is one of the common solid cancers worldwide with well-known etiologic factors including smoking abuse, alcohol consumption as well as HPV infection, etc. [1]. Oral squamous cell carcinoma (OSCC) is one of the common solid cancers worldwide with well-known etiologic factors including smoking abuse, alcohol consumption as well as HPV infection, etc. Despite significant progress in the combined and sequential treatment for OSCC in the last decades, the long-term survival rate has not been remarkably improved [2]. Much efforts have been made to unravel the genetic and epigenetic abnormalities behind OSCC pathogenesis and enable us to capture the mechanistic insights into oral cancer progression [3]. Until now, few biomarkers have been unequivocally established for diagnostic and prognostic management of oral cancer. This unmet challenge significantly impedes the improvement of patients’ treatment outcomes [4]. The novel biomarkers discovery and validation is urgent and of great importance for early detection, novel therapeutics development, leading to improved prognosis
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