Preoperative Serum Selenium Concentrations and Disease-Specific Survival in Patients With Oral Cancer: A Long-Term Follow-Up Study.

BACKGROUND: Serum selenium (Se) concentration has been reported to be associated with the incidence of oral cancer. The association between serum Se and long-term survival in oral cancer patients is still unclear. PURPOSE: The purpose of this study is to measure the association between serum Se and disease-specific survival (DSS). STUDY DESIGN, SETTING, AND SAMPLE: This was a single-center, prospective cohort study conducted at the First Affiliated Hospital of Fujian Medical University (Fujian Province, China) from September 2011 to December 2018. The inclusion criteria were patients with newly diagnosed primary oral cancer confirmed by histology. The exclusion criteria were patients with recurrent oral cancer or metastatic cancer. PREDICTOR VARIABLE: The predictor variable is the preoperative serum Se concentration measured using inductively coupled plasma-mass spectrometry. MAIN OUTCOME VARIABLE(S): The primary outcome variable is DSS calculated from the date of diagnosis to the date of death due to oral cancer or the end of follow-up, whichever occurred first. COVARIATES: The covariates were age, sex, occupation, education level, body mass index, surgery therapy, adjuvant therapy, tumor node metastasis stage, and pathological grading. ANALYSES: Kaplan-Meier survival analysis, Cox proportional hazards regression, and restricted cubic spline regression were utilized. P value < .05 was significant. RESULTS: The sample was composed of 235 subjects with a median age of 59 years (ranged from 20 to 80 years) and 142 (60.43%) were male. The median follow-up was 54.90 months (interquartile range: 35.47). Se levels were associated with DSS (unadjusted hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.54-0.91) suggesting that higher levels of Se are associated with longer or improved DSS. After adjustment of age, sex, occupation, education level, residence, tumor node metastasis stage, pathological grading, surgery therapy, radiotherapy, and chemotherapy, patients with higher serum Se had a better DSS (aHR = 0.67; 95% CI: 0.49-0.92). Of note, we found that the association between serum Se and DSS was observed only in patients with radiotherapy (aHR = 0.49; 95% CI: 0.33-0.73). And the protective effect of radiotherapy on survival was only observed in patients with higher Se concentrations (aHR = 0.36; 95% CI: 0.20-0.63). Additionally, there was a multiplicative interaction between Se and radiotherapy on the prognosis of oral cancer patients (Pinteraction<0.01). CONCLUSION AND RELEVANCE: Our findings suggest that a high Se concentration might contribute to better DSS among oral cancer patients, and the effect may partly depend on radiotherapy treatment. Given these findings, additional research should focus on the role of Se in DSS among oral cancer patients and the interaction with radiotherapy.

Computed tomography/magnetic resonance imaging for mandibular boundary invasion of oral squamous cell carcinoma assessment.

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

Exosomal hsa_circRNA_047733 integrated with clinical features for preoperative prediction of lymph node metastasis risk in oral squamous cell carcinoma.

BACKGROUND: To evaluate whether exosomal circRNAs could serve as diagnostic biomarkers for the accurate preoperative prediction of lymph node metastasis (LNM) risk in oral squamous cell carcinoma (OSCC) patients. METHODS: A combinative strategy of exosomal circRNAs microarray and qRT-PCR verification was employed to dig LNM-related circRNA signatures. Then, a dynamic nomogram was developed based on candidate circRNAs and preoperative clinical features and the calibration, discrimination, and clinical use of the nomogram were evaluated. RESULTS: According to the microarray, three circRNAs derived from the tumor were associated with preoperative LNM risk, including hsa_circRNA_047733, hsa_circRNA_024144 and hsa_circRNA_403472. The hsa_circRNA_047733 was further verified to be significantly downregulated in patients with LNM (+) as compared with those with LNM (-) (p = 0.007). Patients with the higher expression of hsa_circRNA_047733 showed a lower risk of LNM (multivariate-adjusted OR = 0.22, 95%CI: 0.06-0.83). The bioinformatics prediction showed that hsa_circRNA_047733 might sponge miR-4464/miR-4748 to regulate RPS21 expression. A dynamic nomogram integrating exosomal hsa_circRNA_047733 with five clinicopathological characteristics (tumor site, leukocyte level, maximum tumor diameter, and LNM reported by MRI and preoperative biopsy differentiation) was developed. The model displayed an excellent discrimination ability (AUC = 0.868, 95%CI: 0.781-0.955) and great calibration. The decision curve revealed a higher net benefit superior to the baseline model at an 80% threshold probability. CONCLUSION: The data provide preliminary evidence that exosomal hsa_circRNA_047733 might be a novel biomarker for the LNM of OSCC. The hsa_circRNA_047733-based dynamic nomogram could serve as a convenient preoperative assessment tool to predict the risk of LNM for OSCC patients.

Prognostic value of pretreatment lymphocyte percentage in oral cancer: A prospective cohort study.

OBJECTIVE: To assess the prognostic role of pretreatment lymphocyte percentage (LY%) for patients with oral squamous cell carcinoma (OSCC). METHODS: A large-scale prospective cohort study between July 2002 and March 2021 was conducted. Propensity score-matched (PSM) analysis and inverse probability of treatment weighting (IPTW) analysis were performed to adjust for potential confounders. Using random survival forest (RSF), the relative importance of pretreatment LY% in prognosis prediction was also assessed. RESULTS: A total of 743 patients were enrolled and followed up (median: 2.75 years, interquartile range: 1.25-4.42 years). A high pretreatment LY% was significantly associated with better disease-specific survival of patients with OSCC (Hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.42, 0.84). The same tendency was observed in PSM (HR = 0.57, 95% CI: 0.38, 0.85) and IPTW analysis (HR = 0.57, 95% CI: 0.40, 0.82). RSF showed that LY% ranked the fifth among importance ranking of all prognostic factors. CONCLUSION: Pretreatment LY% showed a moderate predictive ability, suggesting it might be a valuable tool to predict prognosis for patients with OSCC.

Development and validation of a model for the prediction of disease-specific survival in patients with oral squamous cell carcinoma: based on random survival forest analysis.

OBJECTIVE: To establish a model for predicting the disease-specific survival (DSS) of patients with oral squamous cell carcinoma (OSCC). METHODS: Patients diagnosed with OSCC from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled and randomly divided into development (n = 14,495) and internal validation cohort (n = 9625). Additionally, a cohort from a hospital located in Southeastern China was utilized for external validation (n = 582). RESULTS: TNM stage, adjuvant treatment, surgery, tumor sites, age, grade, and gender were used for RSF model construction based on the development cohort. The effectiveness of the model was confirmed through time-dependent ROC curves in different cohorts. The risk score exhibited an almost exponential increase in the hazard ratio of death due to OSCC. In development, internal, and external validation cohorts, the prognosis was significantly worse for patients in groups with higher risk scores (all log-rank P < 0.05). CONCLUSION: Based on RSF, a high-performance prediction model for OSCC prognosis was created and verified in this study.

Antitumor effect of toosendanin on oral squamous cell carcinoma via suppression of p-STAT3.

BACKGROUND: Toosendanin (TSN) exhibits potent antitumor activity against various tumor cell lines. However, its efficacy against oral squamous cell carcinoma (OSCC) remains unknown. Here, we investigated the effects of TSN on OSCC cells in vitro and verified them in vivo using a patient-derived xenograft (PDX) model. METHODS: The effect of TSN on OSCC cells was investigated by cytotoxicity assays and flow cytometry. The expression of proteins was detected by western blotting. An OSCC PDX model was constructed to further investigate the role of TSN in regulating the function of OSCC. RESULTS: The cell viability of CAL27 and HN6 cells decreased as the concentration of TSN increased within the experimental range. Compared with controls, TSN at lower doses inhibited cell proliferation and induced apoptosis through S-phase cell cycle arrest. TSN inhibited OSCC cell proliferation by downregulating the STAT3 pathway through the inhibition of STAT3 phosphorylation. After successful construction of the OSCC PDX model with high pathological homology to the primary tumor and treatment with an intraperitoneal injection of TSN, we showed that TSN significantly reduced the tumor size of the PDX model mice without obvious toxicity. CONCLUSIONS: Both in vitro and in vivo, TSN significantly inhibits the proliferation and promoted apoptosis of OSCC cells. Furthermore, TSN demonstrates potent inhibition of STAT3 phosphorylation, indicating its potential as a promising therapeutic agent for OSCC. Therefore, TSN holds great promise as a viable drug candidate for the treatment of OSCC.

Expression of cartilage oligomeric matrix protein (COMP) associates with capsular invasion in salivary gland pleomorphic adenoma.

BACKGROUND: Accumulating evidence shows that pleomorphic adenoma (PA) exhibits a unique capsular invasion and with a crucial role in recurrence. This study was designed to explore RNA expression profiles in salivary gland PA in an attempt to further analyse genes associate with capsule invasion. METHODS: We evaluated the expression profiles of 4 salivary gland PA patients by RNA-sequencing. The principal functions of the differentially expressed mRNAs (DEGs) were explored using GO and KEGG analysis. Then, RT-qPCR and correlation analyses were performed to verify the candidate DEGs in 59 PA patients, and immunohistochemical examinations were conducted to validate candidate DEGs. Finally, the COMP-related genes were screened using correlation and biological pathway enrichment analysis, and further validated by RT-qPCR. RESULTS: A total of 974 DEGs were significantly upregulated, and 1464 were downregulated (fold change ≥2.0; p < 0.05). Based on GO and KEGG analyses, extracellular matrix organization and the PI3K-Akt signalling pathway might play pivotal roles in the tumorigenesis of PA. 40 DEGs were screened and validated by RT-qPCR, 11 upregulated and 5 downregulated DEGs were consistent with the sequencing results. Cartilage oligomeric matrix protein (COMP) was identified to have a significant correlation with the capsular invasion of PA and expression of COMP in patients with invasive capsular PA was significantly stronger than PA. Finally, further results could reveal that 5 highest scoring genes were screened as hub genes for COMP. CONCLUSIONS: These findings suggested that COMP may be a prognostic target for PA and might contribute to its capsular invasion.

High expression of Notch2 drives tongue squamous cell carcinoma carcinogenesis.

Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC.

Mediation analysis of erythrocyte lipophilic index on the association between BMI and risk of oral cancer.

AIMS: To explore the relationship between the fatty acid lipophilic index (LI) of the erythrocyte membrane and oral cancer risk, as well as to evaluate the possibility of LI acting as a mediator of the association between body mass index (BMI) and oral cancer. METHOD: Twenty-three fatty acids (FAs) of the erythrocyte membrane were measured using gas chromatography in 380 patients with oral cancer and 387 control subjects. The LI was calculated based on the FA proportion and FA melting points. The association of BMI and erythrocyte LI with oral cancer risk was analysed using logistic regression. The mediation effect of LI on the association between BMI and oral cancer risk was evaluated using mediation analysis. RESULTS: Among the control group, 46.0% were overweight or obese, which was significantly higher than that of oral cancer patients (29.5%). Significant differences in erythrocyte membrane saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were observed between the patient and control groups. The proportion of C18:1 n-9 from the MUFA family increased in oral cancer patients (12.67%) compared with controls (12.21%). While the total proportion of n-3 PUFAs decreased in oral cancer patients compared with controls, with C20:5 n-3 decreasing from 0.66 to 0.47%, and C22:6 n-3 decreasing from 5.82 to 4.86%. The LI was lower in the control participants (M = 27.6, IQR: 27.3-27.9) than in the oral cancer patients (M = 28.2, IQR: 27.9-28.5). BMI was inversely associated with oral cancer risk with a fully adjusted OR of 0.59 (95% CI: 0.43-0.83), while LI was positively associated with oral cancer risk with a fully adjusted OR of 1.99 (95% CI:1.36-2.94). LI explained 7% of the variance in the relationship between BMI and oral cancer risk. CONCLUSIONS: The distribution of the FA profile in erythrocyte membranes differed between the oral cancer patients and the control group. The LI derived from the profile of FAs was positively associated with the risk of oral cancer, and the associations between BMI and oral cancer risk can be explained, at least in part, by LI.

A novel nutritional risk score and prognosis of oral cancer patients: A prospective study.

OBJECTIVES: To evaluate the prognostic performance of a novel nutritional risk score based on serum iron, hemoglobin, and body mass index (BMI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: X-tile analysis was performed to determine the optimal cutoff values of serum iron, hemoglobin, and BMI. A nutritional risk score was established by using the HR values of serum iron, hemoglobin, and BMI. Kaplan-Meier curve and multivariable Cox proportional hazards models were used to evaluate the prognostic value of the nutritional risk score in overall survival (OS) and oral cancer-specific survival (OCSS). RESULTS: Serum iron, hemoglobin, and body mass index were all inversely related to the prognosis of oral cancer. The adjusted HR of serum iron, hemoglobin, and BMI were 1.562, 1.886, and 1.465 for OS, and 1.653, 1.865, and 1.443 for OCSS. Patients with higher nutritional risk score had a poorer OS and OCSS. Additionally, chemotherapy was only associated with improved OCSS in patients with the lowest nutritional risk score, but not in patients with higher one. CONCLUSIONS: Nutritional risk score is of prognostic value in oral cancer patients. Favorable response to chemotherapy may only be observed in well-nourished oral cancer patients with lower nutritional risk score.

A novel prognostic score based on systemic inflammatory biomarkers for patients with oral squamous cell carcinoma.

OBJECTIVE: To explore the prognostic value of systemic inflammatory biomarkers (albumin/globulin ratio [AGR], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR]) in patients with oral squamous cell carcinoma (OSCC), and further develop a novel prognostic score (AGR-NLR). METHODS: A large-scale prospective study enrolling 792 eligible patients from December 2002 to June 2018 was carried out at the First Affiliated Hospital of Fujian Medical University. Three multivariate Cox regression models were performed to assess the association of overall survival (OS) with systemic inflammatory biomarkers, quantified by Akaike information criterion (AIC). Then, a novel AGR-NLR score was established and incorporated into a prognostic nomogram. RESULTS: In the univariate analysis, the increased AGR was associated with a reduced risk of death. Conversely, the higher NLR and PLR, the worse the OS. In the multivariate Cox regression models, AGR and NLR were stably independent prognostic indicators in all models, with Model 2 showing a lowest AIC (AGR: HR = 0.56, 95%CI: 0.41-0.78; NLR: HR = 1.80, 95%CI: 1.07-3.04). Then, a novel AGR-NLR score was established, which showed a more excellent performance than either AGR or NLR alone (area under curve [AUC]: 0.589, 0.559, and 0.556, respectively). The C-index of the nomogram based on AGR-NLR was superior to that of traditional TNM staging system (C-index: 0.658 versus. 0.596, p < .001). Similar results were also showed by decision curve analysis, indicating the nomogram had more positive net benefit compared to TNM staging system. CONCLUSION: The novel AGR-NLR score is strongly associated with outcome in patients with OSCC and could be serve as a useful tool to accurately predict the OS of OSCC patients.

A composite oral hygiene score and the risk of oral cancer and its subtypes: a large-scale propensity score-based study.

OBJECTIVE: This study aimed to investigate the potential relationship between oral hygiene and the risk of oral cancer and its subtypes after controlling the effects of several confounding factors. MATERIALS AND METHODS: A large-scale case-control study was conducted from January 2010 to August 2019, recruiting a total of 1,288 oral cancer cases with newly diagnosed and 4,234 healthy controls. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to minimize confounding effects. Conditional logistic regression was used to evaluate the effects of oral hygiene indicators on oral cancer. RESULTS: A composite oral hygiene score was developed based on five indicators selected based on PSM and IPTW analysis (including tooth loss, dentures wearing, the frequency of tooth brushing, regular dental visits, and recurrent dental ulcer). Participants with a higher score, compared with their lower counterparts, showed a 49% increased risk (the odds ratio (OR) was 1.49 (95% confidence interval (CI): 1.26-1.75). A similar association pattern was found following IPTW analyses (OR = 1.32; 95% CI: 1.22-1.42). Of note, the adverse effects of poor oral hygiene were more evident among the sites of gingival and buccal (PSM analysis: 2.03-fold and 2.68-fold increased risk; IPTW analysis: 1.57-fold and 2.07-fold increased risk, respectively). Additionally, a greater positive association was observed between poor oral hygiene and oral squamous cell carcinoma, compared with other pathological types. CONCLUSION: This study establishes a composite oral hygiene score and provides supportive evidence of poor oral hygiene associated with a higher risk of oral cancer, particularly in the gingival and buccal mucosa sites and in the squamous cell carcinoma. CLINICAL RELEVANCE: The data highlights the importance of improving poor oral hygiene habits, which has public health implications for the prevention of oral cancer.

Prognostic value of preoperative lymphocyte-to-monocyte ratio in oral cancer patients and establishment of a dynamic nomogram.

OBJECTIVE: To assess the association of preoperative lymphocyte-to-monocyte ratio (LMR) and overall survival (OS) in patients with oral cancer and develop a dynamic nomogram for individualized survival prediction. METHOD: The prognostic value of LMR was evaluated in a large-scale cohort with 651 postoperative patients with oral cancer between January 2010 and December 2017. Propensity score-matched (PSM) analysis and inverse probability of treatment weighting (IPTW) analysis were performed to further verify the prognostic value of LMR. A dynamic nomogram was then developed based on the LMR and clinicopathological features, and its predictive performance and clinical utility were evaluated. RESULTS: A high LMR was significantly associated with better OS of patients with oral cancer (HR = 0.65; 95% CI = 0.44-0.98). The similar association was also observed in the PSM and IPTW analyses. Moreover, compared with TNM staging system, the dynamic nomogram based on the LMR exhibited more excellent predictive performance (0.72 versus 0.64, p < .001), with calibration curves (1,000 bootstrap resamples) suggesting good match between the actual and predicted probabilities. Decision curve analyses (DCAs) showed a more significant positive net benefit in the practical ranges of threshold probabilities using the dynamic nomogram. CONCLUSION: Preoperative LMR may serve as an easily accessible and non-invasive prognostic biomarker for predicting the prognosis of patients with oral cancer. A dynamic nomogram based on the LMR may show more convenience in survival prediction for patients with oral cancer. Further future studies are warranted to confirm our findings.

Analysis of Maxillofacial Fractures Based on the Etiology in Southeast China: A 10-Year, Multi-Center Study.

BACKGROUND: The aim of this study was to explore the characteristics and correlation of maxillofacial fractures and concurrent injuries with different injury causes. METHODS: In this retrospective study, data were collected from patients treated for maxillofacial fractures in 3 oral and maxillofacial surgery departments in Southeast China, from January 2010 to December 2019. The information was obtained from clinical notes and surgical records using a standardized data collection form, and some causes of injuries were confirmed by telephone follow-ups and police records. These patients were divided into 7 groups according to the etiology: bicycle accident, electric bicycle accident, motorcycle accident, automobile accident, fall at ground level, fall from a height, and assault-related accident. Statistical tests were performed using R software (version 3.1.1), and all P-values were computed based on Chi-square tests and set at 0.05. RESULTS: During this 10-year retrospective study, a total of 1772 patients with definite causes were analyzed. The average age was approximately 35.04 years (9 months-94 years). All patients were treated with open reduction and rigidly internal fixation, and the average duration was approximately 6.51 days (range 0 day-50 days), that from the time of the injury to the time of treatment. Traffic accidents were identified as the main cause of maxillofacial fracture (57.62%; n = 1021 of 1772 cases). In different etiology groups, there were statistically significant differences in the distribution of age, sex, maxillofacial fracture type, and concurrent injuries (all P < 0.001). However, the main cause of maxillofacial injuries was falls (fall at ground level and fall from a height) in children, and the highest incidence of the cause of maxillofacial injuries was bicycle accident in adolescents. Compared with the other groups, zygomatic complex fracture was more common in the electric bicycle accident group, panfacial fracture was more common in the automobile accident group, and mandible fracture was more common in the other groups. CONCLUSION: The results of this study suggest that patients with maxillofacial fractures caused by different injuries had their own unique characteristics. These findings may assist us in avoiding misdiagnosis and treatment delays, and may make treatment plans faster.

The effect of formal statistical courses attitudes on learning outcomes in a cohort of undergraduate dental students.

INTRODUCTION: Whilst statistical knowledge is essential for dental students' academic or professional careers, only a few studies have measured the attitudes of these students towards statistics courses. This study aimed to investigate the attitudes of a cohort of dental students towards a formal statistical course and explore the factors that are potentially related to these attitudes. METHODS: A survey was performed amongst dental students of 2017 entry at Fujian Medical University, China. The questionnaire covers three aspects: demographic characteristics, educational background and attitudes towards formal statistics courses. RESULTS: A total of 103 dental students enrolled for the survey, and the response rate was 100.0%. 44.7% of dental students had positive attitudes towards formal statistics courses with an overall average of 25.7 (SD = 2.2, out of 30). Students' computer skills, expectations of course achievement, attention in class and learning atmosphere of the class were significantly associated with the attitudes towards formal statistics courses. Moreover, students with positive attitudes experienced a greater improvement in the statistical cognition and application ability of statistical methods after the course than those with negative/neutral attitudes. Additionally, a positive correlation was observed between students' attitudes and achievement in the examination. CONCLUSION: These results suggest that attitudes are critical to the learning effectiveness in formal statistics courses amongst undergraduate dental students. All the educators involved should monitor the students' attitudes in the teaching process and make effective interventions to improve students' attitudes towards formal statistics courses.

[Correlation between serum iron level and overall survival of oral cancer].

OBJECTIVE: To explore the correlation between serum iron(Fe) and the overall survival of oral cancer. METHODS: Patients with oral cancer who met the inclusion criteria in the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Fujian Medical University from January 2010 to April 2017 were collected. The average age was(57.12±13.94) years old, including 489 males(65.46%), 258 females(34.54%) and 564 cases of squamous cell carcinoma(77.90%). Overall survival rates were calculated by Kaplan-Meier method. Survival difference was compared by log-rank test. Cox regression model was used to estimate the hazard ratio(HRs) and 95% confidence intervals(95%CIs). RESULTS: The distributions of serum iron level were non-normal distribution(P<0.001), and the serum iron level is expressed as 13.9(10.3, 17.8)µmol/L in M(P25, P75). According to X-tile, the optimal cut-off value of serum iron was 15.3 µmol/L, used as a criterion to group patients. The result showed that the mortality risk of patients with oral cancer in high serum iron level(Fe>15.3 µmol/L) was 0.72 times of patients in lower one(Fe≤15.3 µmol/L)(95%CI 0.52-0.99). Stratified analysis suggested that serum iron was a good predictor of patients with oral cancer aged 60 years(HR=0.62, 95%CI 0.39-0.99), male(HR=0.66, 95%CI 0.44-0.98), with TNM stage I-II(HR=0.42, 95%CI 0.20-0.88) and squamous cell of pathological type(HR=0.69, 95%CI 0.49-0.97). CONCLUSION: Serum iron is closely related to the overall survival of oral cancer, patients with high serum iron have a lower risk of death.

[Association between hypertension and oral cancer prognosis in non-smoking and non-drinking women].

OBJECTIVE: To explore the association between hypertension and prognosis of oral cancer patients in non-smoking and non-drinking women. METHODS: From September 2010 to February 2019, 362 non-smoking and non-drinking female patients with pathologically confirmed oral cancer were recruited and followed up in the First Affiliated Hospital of Fujian Medical University. The patients were divided into hypertension group and non-hypertensive group, and the Kaplan-Meier method was performed to calculate the cumulative survival rate. The survival curve was tested by the log-rank method for differences between the two groups. Cox proportional regression model was utilized to explore the prognostic factors. 1∶1 propensity score matching was applied in order to verify the above findings. Stratified analysis was used to explore the prognosis of oral cancer treated by different method and fish intake between two groups respectively. RESULTS: The Cox proportional hazards model showed that the risk of death of hypertension patients was 1.976 times than nonhypertensive patients(95%CI 1.003-3.890), the risk of death for patients with lymph node metastasis was 2.938 times than patients without metastasis(95%CI 1.318-6.551), the risk of death for patients underwent surgery combined with adjuvant therapy was 0.454 times than surgery alone(95%CI 0.236-0.875). After propensity score matching, the Cox proportional hazard model showed that the risk of death for patients with hypertension was 2.987 times than non-hypertensive patients(95%CI 1.050-8.497). The result of stratified analysis showed that the risk of death for non-hypertensive patients with surgery combined with adjuvant therapy was 0.233 times than patients with surgery alone(95%CI 0.085-0.643) and the risk of death in patients with hypertension who consumed fish ≥3 times/week was 0.020 times higher than that in women with oral cancer who consumed fish<3 times/week(95%CI 0.001-0.392). CONCLUSION: Hypertension is an independent prognostic factor for oral cancer in non-smoking and non-drinking women. Non-hypertensive patients underwent surgery combined with adjuvant therapy can reduce the risk of death and the increase of fish intake can improve the prognosis of hypertensive female oral cancer patients.

Nutritional assessment and prognosis of oral cancer patients: a large-scale prospective study.

BACKGROUND: To evaluate and compare the prognostic performance of four nutritional indicators body mass index (BMI), serum albumin (ALB), prognostic nutritional index (PNI) and nutritional risk index (NRI) in oral cancer patients, and to predict the response to chemotherapy in patients with different nutritional status. METHODS: This prospective study which involved 1395 oral cancer patients was conducted in Fujian, China from September 2007 to November 2018. The BMI, PNI and NRI were calculated according to the following formulas: BMI = weight / height2 (kg/m2), PNI = albumin (g/l) + 0.005 × lymphocyte (count/µl) and NRI = (1.519 × albumin, g/l) + (41.7× present/ideal body weight), respectively. The univariate and multivariate Cox proportional hazards models were used to compare the prognostic value of BMI, ALB, PNI and NRI in overall survival (OS) in oral cancer. RESULTS: Patients with BMI < 18.5 kg/m2 (VS 18.5 kg/m2 ≤ BMI < 24 kg/m2) had a poor survival outcome (HR = 1.585; 95% CI: 1.207-2.082 ). ALB, PNI, NRI were inversely correlated with OS of oral cancer (HR = 0.716; 95% CI: 0.575-0.891; HR = 0.793; 95% CI: 0.633-0.992; HR = 0.588; 95% CI: 0.469-0.738, respectively). In addition, the prognostic predictive performance of NRI was superior to BMI or ALB or PNI. Interestingly, compared with patients with better nutritional status, chemotherapy was significantly associated with poorer OS in malnourished oral cancer patients. CONCLUSIONS: BMI, ALB, PNI and NRI are of prognostic value in patients with oral cancer and the prognostic performance of NRI was superior to BMI or ALB or PNI. Malnutrition (BMI < 18.5 kg/m2 or ALB< 40 g/l or PNI < 49.3 or NRI < 97.5) could predict an unfavorable response to chemotherapy in oral cancer patients.

Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma.

BACKGROUND: Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear. METHODS: The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model. RESULTS: We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo. CONCLUSIONS: MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.

Prognostic value of transforming growth factor beta receptor 1 polymorphisms in patients with oral cancer.

OBJECTIVE: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1). METHODS: Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer. RESULTS: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed. CONCLUSIONS: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings.