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Objectives: Mandibular resection for oral cancer is often necessary to achieve an adequate margin of tumor clearance. Mandibular resection has been associated with a poor health-related quality of life (HRQOL), particularly before free fibula flap to reconstruct the defect. The aim of this study was to evaluate health-related quality of life in patients who have had mandibular resections of oral cancer and reconstruction with free fibula flap. Study Designs: There were 115 consecutive patients between 2008 and 2011 who were treated by primary surgery for oral squamous cell carcinoma, 34 patients had a mandibular resection. HRQOL was assessed by means of the 14-item Oral Health Impact Profile (OHIP-14) and University of Washington Quality of Life (UW-QOL) questionnaires after 12 months postoperatively. Results: In the UW-QOL the best-scoring domain was mood, whereas the lowest scores were for chewing and saliva. In the OHIP-14 the lowest-scoring domain was social disability, followed by handicap, and psychological disability. Conclusions: Mandible reconstruction with free fibula flap would have significantly influenced on patients’quality of life and oral functions. The socio-cultural data show a fairly low level of education for the majority of patients. Key words:Health-related quality of life, free fibula flap, mandibulectomy, UW-QOL, OHIP-14.

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Oct4 and Sox2 are pluripotent stem cell factors but the interplay between them in tumorigenesis is unclear. The aim of the present study was to investigate the roles of Oct4 and Sox2 in the reprogramming of oral cancer stem cells. One or both Oct4 and Sox2 were overexpressed in immortalized oral epithelial (hTERT+-OME) cells by lentivirus transduction. In addition, Oct4 and Sox2 proteins in two oral squamous cell carcinoma cell (OSCC) lines (Cal27 and primary cultured OSCC from a T2N2M0 patient) were individually or combinedly knocked down by shRNA. The results showed that the doubly transduced (Oct4+Sox2+) cells could trigger neoplasms in immunodeficient mice after lentivirus transduction, but single transduced (Oct4+ or Sox2+) cells had no tumor formation ability. The knockdown Sox2low and knockdown Oct4lowSox2low cells resulted in decreased tumor size in the immunodeficient mice but the single knockdown Oct4low cancer cells acquired more aggressive xenografts. Our findings suggest that Oct4+Sox2+ cells may be reprogrammed cancer stem cells inducing oral carcinogenesis.

Oral cancer is the most common malignant tumor in the oral and maxillofacial region, of which more than 90% is squamous cell carcinoma. The incidence of oral cancer is on the rise worldwide. An imbalance between the microorganism composition and its host may lead to the occurrence of oral malignant tumors. Accumulating evidence suggests that the oral microbiota plays an important role in oral cancer; however, the association between oral microbiota and oral cancer has not yet been comprehensively studied. In this study, metagenomic sequencing was used to compare the microbial composition of three groups of samples from Chinese patients with oral cancer, patients with precancerous lesion, and normal individuals. In terms of microbiota richness, the oral microbiota of patients with precancerous lesions was richer than that of oral cancer patients and healthy controls, whereas in terms of microbiota diversity, there was little difference between the three groups. The three groups of samples exhibited statistically significant differences in microbiota composition and metabolic function at the family, genus, and species levels (P < 0.05). The differentially enriched phylum in oral cancer samples was Bacteroidetes (P < 0.05). At the genus level, the main differentially enriched taxa were Prevotella, Peptostreptococcus, Carnobacterium, and Diastella (P < 0.05). The species level was differentially enriched in Prevotella intermedia and Peptostreptococcus stomatis (p < 0.05). The prediction of microbiota function shows that oral cancer is mainly associated with coenzyme A biosynthesis, phosphopantothenic acid biosynthesis, inosine 5’-phosphate degradation, and riboflavin biosynthesis. Furthermore, the increase in C-reactive protein level in oral cancer patients was found to be closely related to P. intermedia. Overall, oral bacterial profiles showed significant differences between the oral cancer group and normal group. Hence, microbes can be employed as diagnostic markers and treatment targets for oral cancer.

Objective: Accurate predictors for occult metastasis in cT1-2N0 tongue squamous cell carcinoma (SCC) remains scarce, the main goal in current study was to evaluate whether there is significant association between lingual lymph node (LLN) metastasis and occult lymph node metastasis as well as whether there is prognostic value of LLN metastasis in early stage tongue SCC. Methods: Patients with surgically treated primary cT1-2N0 tongue SCC were prospectively enrolled from January 2010 to December 2018. LLNs were dissected independently for pathologic analysis. The main study endpoints were locoregional control survival (LRC) and disease-specific survival (DSS). The Chi-square test and multivariate regression analysis were used to assess the predictors for occult metastasis. The Kaplan-Meier approach and Cox model were used to analyze the potential prognostic factors. Results: A total of 317 patients were enrolled for analysis. Eighty-eight patients had occult metastasis with a prevalence of 27.8%. LLNs presented in 89 patients, in which 43 patients had LLN metastasis. In the 43 patients with positive LLNs, 20 patients had occult metastasis, in 274 patients with negative LLNs or no LLNs, 68 patients had occult metastasis, the difference was significant (p = 0.012). Further multivariate regression analysis confirmed the independence of LLN metastasis in predicting the occult metastasis. In patients without LLNs, the 5-year LRC rate was 79%, in patients with negative LLNs, the 5-year LRC rate was 78%, in patients with positive LLNs, the 5-year LRC rate was 62%, the difference was significant (p = 0.024). In patients without LLNs, the 5-year DSS rate was 84%, in patients with negative LLNs, the 5-year DSS rate was 74%, in patients with positive LLNs, the 5-year DSS rate was 51%, the difference was significant (p < 0.001), further Cox model confirmed the independence of LLN metastasis in affecting the LRC and DSS. Conclusions: LLN metastasis is significantly associated with occult neck lymph node metastasis, and decrease the LRC and DSS in early stage tongue SCC.

The aim of this study was to explore the functions and associated mechanisms of long noncoding RNA LINC02487 in oral squamous cell carcinoma (OSCC). Methods:The relative expression levels of LINC02487 in OSCC cell lines and tissue samples were examined by RT-qPCR. Intracellular localization was determined using RNA fluorescence in situ hybridization. LINC02487 was cloned into the pCMV-puro vector and then introduced into OSCC cells using lentiviral transfection. Cell processes, such as proliferation, apoptosis, migration, and invasion, were subsequently examined. LINC02487-binding proteins were identified by ChIRP-MS and confirmed by RNA immunoprecipitation. Protein expression was determined by western blotting assay.Results: LINC02487 has been reported to be downregulated in OSCC. Here, we confirmed that the expression of LINC02487 was reduced in 6 OSCC cell lines compared with that in immortalized normal oral epithelial cells and in 50 OSCC samples compared with paired adjacent normal tissue in a Chinese population and that LINC02487 expression levels were associated with cancer metastasis. We further identified that LINC02487 was localized to the cytoplasm, aggregated around the nuclear membrane. Functional studies demonstrate that overexpression of LINC02487 significantly suppresses cell migration and invasion and also inhibits cell proliferation. For the mechanism, we reveal that LINC02487 directly binds to USP17, a deubiquitinating enzyme, and regulates cell migration and invasion through the USP17-SNAI1 axis in a process that involves epithelial-mesenchymal transition (EMT). Conclusion:Our results confirm that long noncoding RNA LINC02487 is downregulated in OSCC tissue samples and cell lines. We also find that LINC02487 acts as a tumor suppressor through the USP17-SNAI1 axis.

BackgroundPiwi-interacting RNAs (piRNAs) are thought to silence transposable genetic elements. However, the functional roles of piRNAs in oral squamous cell carcinoma (OSCC) remain unelucidated. In the present study, we aimed to investigate the role of Piwi-interacting RNA 1037 (piR-1037) in chemoresistance to cisplatin (CDDP)-based chemotherapy and the oncogenic role of piR-1037 in OSCC cells.MethodsRT-PCR was used to evaluate the levels of piR-1037 and X-linked Inhibitor of apoptosis protein (XIAP) mRNA in OSCC cell lines or tumor xenografts. Transfection of piR-1037 DNA antisense and piR-1037 RNA oligonucleotides was performed to suppress and overexpress piR-1037 in OSCC cells, respectively. A CCK8 assay was used to measure the viability or proliferation of OSCC cells. Apoptosis in OSCC cells and xenografts was determined using a TUNEL assay kit. The activity of caspase-3, caspase-8 and caspase-1 in OSCC cells was measured with colorimetric caspase assay kits. Western blot analysis was conducted to analyze XIAP expression in OSCC cells and xenograft samples. Immunoprecipitation (IP) and RNA pull-down assays were utilized to analyze the piR-1037 - XIAP interaction. Transwell assays were performed to evaluate migration and invasion of OSCC cells.ResultsCDDP treatment upregulated piR-1037 expression in OSCC cells and OSCC xenografts. Suppression of the CDDP-induced upregulation of piR-1037 expression enhanced the sensitivity of OSCC cells to CDDP. piR-1037 promoted protein expression and directly bound XIAP, a key apoptotic inhibitor that is implicated in chemoresistance. The relationship between piR-1037 and XIAP suggested that piR-1037 enhanced OSCC cell chemoresistance to CDDP at least partially through XIAP. Moreover, targeting the basal expression of piR-1037 inhibited cell motility by affecting epithelial–mesenchymal transition (EMT).ConclusionpiR-1037 enhances the chemoresistance and motility of OSCC cells. piR-1037 promotes chemoresistance by interacting with XIAP and regulates the motility of OSCC cells by driving EMT.