Oral squamous cell carcinoma (OSCC), which is typically preceded by oral leukoplakia (OL), is a common malignancy with poor prognosis. However, the signaling molecules governing this progression remain to be defined. Based on microarray analysis of genes expressed in OL and OSCC samples, we discovered that the long non-coding RNA IFITM4P was highly expressed in OSCC, and ectopic expression or knockdown of IFITM4P resulted in increased or decreased cell proliferation in vitro and in xenografted tumors, respectively. Mechanistically, in the cytoplasm IFITM4P acted as a scaffold to facilitate recruiting SASH1 to bind and phosphorylate TAK1 (Thr187), and in turn to increase the phosphorylation of nuclear factor κB (Ser536) and concomitant induction of PD-L1 expression, resulting in activation of an immunosuppressive program that allows OL cells to escape anti-cancer immunity in cytoplasm. In nucleus, IFITM4P reduced Pten transcription by enhancing the binding of KDM5A to the Pten promoter, thereby upregulating PD-L1 in OL cells. Moreover, mice bearing tumors with high IFITM4P expression had notable therapeutic sensitivity to PD-1 monoclonal antibody (mAb) treatment. Collectively, these data demonstrate that IFITM4P may serve as a new therapeutic target in blockage of oral carcinogenesis, and PD-1 mAb can be an effective reagent to treat OSCC.

Background: Current evidence on diagnostic value of aneuploidy with DNA image cytometry (ICM) using brushings for oral potentially malignant disorders (OPMD) is limited by sample size and inconsistent classification criteria of aneuploidy. This study aimed to explore the optimal cut‐off values of DNA content and evaluate the diagnostic accuracy of DNA‐ICM for detecting dysplasia and/or carcinoma in OPMD.Materials and Methods: A total of 401 consecutive patients with OPMD were enrolled in this prospective diagnostic study. Brushing and biopsy sample form each patient was processed by DNA‐ICM and histological examination respectively.Results: When the optimal cut‐off of at least one aneuploid cell with DNA index (DI) ≥2.3, the area under the curves (AUC) was 0.735 and positive predictive value was 92.7% for detecting dysplasia within OPMD. When the optimal cut‐off of at least one aneuploid cell with DI ≥ 3.5, the AUC was 0.851 and negative predictive values was 96.8% for detecting carcinoma within OPMD. Importantly, multivariate analysis revealed that aneuploidy with DI ≥ 2.3 in OPMD was significantly associated with dysplasia risk (adjusted OR, 5.52; 95%CI, 2.90‐10.51; P < .001), and aneuploidy with DI ≥ 3.5 in OPMD was strongly associated with malignant risk (adjusted OR, 21.05; 95%CI, 9.34‐47.41; P < .001).Conclusions: This largest‐scale diagnostic study optimized the criteria of aneuploidy cytology for noninvasive detection of oral dysplasia and carcinoma within OPMD. DNA aneuploidy in OPMD was an independent marker that strongly associated with oral dysplasia/carcinoma. Our findings suggest that DNA‐ICM may serve as a useful noninvasive adjunctive tool for oral cancer and OPMD screening.

Background: Bibliometric analysis highlights the key topics and studies which have shaped the understanding and management of a disease of interest. Here the top-cited articles on oral leukoplakia (OL) were characterized, and research patterns and trends were analyzed. Methods: A comprehensive search was performed and identified in the Scopus database up to 22 February 2019 for the 100 most-cited articles on OL. Results: The number of citations of the 100 selected articles varied from 116 to 1418, with a mean of 226.7 citations per article. Both Journal of Oral Pathology and Medicine and Oral Surgery Oral Medicine Oral Pathology Oral Radiology were journals with the most articles published (n = 10). Both Hong W.K. and Lippman S. were the most frequently contributing authors (n = 9). United States (n = 43) and M.D. Anderson Cancer Center (n = 12) was most contributing country and institution, respectively. Systematic reviews/meta-analysis (n = 3) and randomized controlled trial (n = 7) were study designs with high evidence level. It is noteworthy that the majority of high-quality articles were the research of chemopreventive drugs (n = 21) and molecular markers/targets (n = 10), which may indicate a trend of key topics. Conclusions: The results of this first citation analysis of the most-cited articles on OL provide a historical perspective on scientific evolution, and suggest further research trends and clinical practice in the field of OL.