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.

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.

Scientific creativity and innovation ability and its determinants among medical postgraduate students in Fujian province of China: a cross sectional study.

BACKGROUND: Graduate education is the main approach to training high-level innovative elites. With the expansion of the scale of graduate education in China, it has gradually emerged that the lack of innovation ability of graduate students is recognized as the primary problem in graduate education. How to comprehensively improve the quality of postgraduate teaching has become the core task of educational reform and development. However, data about the current cultivation and development of the innovative ability of graduate students in China is limited. METHODS: A questionnaire survey was conducted among medical postgraduate students. Descriptive statistics and multiple regression analysis methods were used to analyze the data to describe the current innovation ability in advanced medical education and potential influence factors. RESULTS: A total of 1241 medical students were surveyed, according to the results of questionnaire data analysis. The proportion of subjects who participated in the College Student's Entrepreneurship and Innovation program or any other scientific research programs are fairly high which are 46.82% and 29.20% respectively. Most of the participants are observed with high levels of self-motivation and active learning and have good performance in creative thinking. However, only a small number of participants (16.6%) reported academic achievements such as publications. Most of the students are satisfied with the current scientific research environment and think that the current postgraduate training system is qualified for the cultivation of innovation ability, and expects the inclusion of course specialized in systemic medicine and medical informatics in the curricula. Multiple logistic regression results showed that among the factors studied, gender, medical specialties, and types of master's degrees are associated with cognition & skills, academic performance, and creativity. CONCLUSIONS: It will be important to incorporate more techniques for creating and improving creativity in the curricula of the current postgraduate education, especially for courses such as systemic medicine and informatics. Guidance in earlier school life can stimulate creativity and an early introduction to scientific research work will facilitate innovative thinking and behavior. Scientific research programs such as the National Innovation and Entrepreneurship Training for the universities of PRC have been widely implemented in the undergraduate education system throughout the country. However, the training effectiveness of the current scientific research programs is worth improving.

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.

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.

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.

Selenoprotein genetic variants may modify the association between serum selenium and oral cancer risk.

OBJECTIVE: The relationship between selenium (Se) and oral cancer is still controversial, and the selenoprotein genes play crucial roles in selenium metabolism. We aim to investigate the potential effect of selenoprotein genes (including GPx and TXNRD) in the association of serum Se with oral cancer risk. METHODS: A case-control study including 235 oral cancer cases and 406 controls from September 2011 to December 2018 was conducted in Fujian, China. The peripheral blood samples were obtained from each participant. Genotyping was performed by MassARRAY system, and serum Se levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Compared with the lowest tertile of Se concentration, those with Se levels in the third tertile were associated with the lower risk of oral cancer (OR = 0.228; 95% CI: 0.135, 0.384). After additional adjustment for genetic risk score (GRS, derived from selenoprotein genetic variants), the model demonstrated the superior goodness of fit. When stratified by GRS, the negative correlation of serum Se was more pronounced among those with low risk (i.e., lower GRS). Moreover, there is a multiplicative interaction between serum Se and GRS for the risk of oral cancer (p = .001). CONCLUSIONS: The present study suggests that serum Se levels may be significantly associated with oral cancer risk, yet the association may be modified by the effects of selenoprotein genetic variants.

Postoperative dynamic survival of gastric cancer patients: A multi-institutional, international analysis of 22 265 patients.

BACKGROUND: How to best evaluate the disease-specific survival (DSS) of gastric cancer (GC) survivors over time is unclear. METHODS: Clinicopathological data from 22 265 patients who underwent curative intend resection for GC were retrospectively analyzed. Changes in the patients' 3-year conditional disease-specific survival (CS3) were analyzed. We used time-dependent Cox regression to analyze which variables had long-term effects on DSS and devised a dynamic predictive model based on the length of survival. RESULTS: Based on 1-, 3-, and 5-year survivorships, the CS3 of the population increased gradually from 62% to 68.1%, 83.7%, and 90.6%, respectively. Subgroup analysis showed that the CS3 of patients who had poor prognostic factors initially demonstrated the greatest increase in postoperative survival time (eg, N3b: 26.6%-84.1%, Δ57.5% vs N0: 84.1%-93.3%, Δ9.2%). Time-dependent Cox regression analysis showed the following predictor variables constantly affecting DSS: age, the number of examined lymph nodes (LNs), T stage, N stage, and site (P < .05). These variables served as the basis for a dynamic prediction model. CONCLUSIONS: The influence of prognostic factors on DSS and CS3 changed dramatically over time. We developed an effective model for predicting the DSS of patients with GC based on the length of survival time.

Serum copper and zinc levels and the risk of oral cancer: A new insight based on large-scale case-control study.

OBJECTIVE: Limited evidence exists on the roles of serum copper (Cu) and zinc (Zn) in oral cancer risk. We aimed to preliminarily explore the association between serum Cu and Zn levels and oral cancer risk with relatively large-scale samples. METHODS: Serum Cu and Zn levels of 344 oral cancer patients and 1,122 matched healthy controls in this case-control study were measured by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Restricted cubic spline revealed the U-shaped relationship between serum Cu or Zn levels and the risk of oral cancer. Serum deficient or elevated levels of Cu were significantly associated with the risk of oral cancer: The ORs were 1.38 (95% CI: 1.01-1.89) and 2.82 (95% CI: 1.60-4.98), respectively. The positive association of serum low or high levels of Zn with oral cancer risk was also observed: The ORs were 2.72 (95% CI: 1.60-4.62) and 12.41 (95% CI: 9.09-16.93), respectively. Additionally, there were multiplicative interactions between the aforementioned trace elements and smoking. CONCLUSIONS: This preliminary study suggests that both serum excess and deficient levels of Cu or Zn were significant correlation with oral cancer risk, which may provide a new insight on the roles of serum Cu and Zn in oral cancer.

TUSC2P suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and correlates with disease prognosis.

BACKGROUND: Pseudogenes are RNA transcripts with high homology with its parent protein-coding genes. Although pseudogenes lost the ability to produce protein, it still exert import biological function, and play important role in the pathogenesis of a wide varity of tumors; However, the role of pseudogenes in esophageal squamous cell carcinoma (ESCC) is poorly understood. METHODS: TUSC2P function in ESCC were explored using both in vitro and in vivo experiments cell proliferation, invasion and apoptosis assay was performed to evaluated the effect of TUSC2P on the tumor biology of ESCC. Expression of relative genes was assessed by quantitative real-time PCR (qRT-PCR) and western blotting in EC109 and TE-1 cell, as well as ESCC patients. 3'UTR luciferase assay was used to confirm the direct binding of miRNAs with TUSC2 and TUSC2P 3'UTR. Relation betweenTUSC2P, TUSC2 and ESCC prognosis was predicted by survival analysis (n = 56). RESULTS: Pseudogene TUSC2P was down regulated in ESCC tissues compared with paired normal adjacent tissues, and the expression of TUSC2P was significantly correlated with survivalof ESCC patients. Over expression of TUSC2P in EC109 and TE-1 cells resulted in altered expression of TUSC2, thus inhibited proliferation, invasion and promoted apoptosis. Dual luciferase assay demonstrated that TUSC2P 3'UTR decoyed miR-17-5p, miR-520a-3p, miR-608, miR-661 from binding to TUSC2. CONCLUSIONS: TUSC2P can suppresses the tumor function of esophageal squamous cell carcinoma by regulating TUSC2 expression and may also serve as a prognostic factor for ESCC patients.

MiRNA-17 encoded by the miR-17-92 cluster increases the potential for steatosis in hepatoma cells by targeting CYP7A1.

BACKGROUND: The miRNA cluster miR-17-92 is known to act as an oncogene in various cancers. Members of this cluster were also found to be involved in some other pathological process, such as steatosis, which is a pivotal event in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether miR-17, one of the most functional miRNAs in the miR-17-92 family, participates in the process of steatosis in hepatoma cells. METHODS: We developed both a miR-17-expressing transgenic mouse model and a miR-17-expressing HepG2 cell model, the latter was established via stable transfection. Real-time PCR and western blot were applied to measure the expression levels of miR-17 and the potential target gene CYP7A1. The luciferase assay was used to confirm direct binding of miR-17 and CYP7A1. The oleic acid induction assay and Oil-Red-O staining were performed to support the determination of steatotic changes in HepG2 cell. RESULTS: Extensive steatotic changes were observed in the livers of transgenic mice. Fewer were seen in the wild-type animals. CYP7A1 was confirmed as a target gene of miR-17, and the expression of CYP7A1 was found to be negatively regulated in both the transgenic mice liver cells and the miR-17-expressing HepG2 cells. CYP7A1 was found to participate in miR-17-induced steatosis, as its repressed expression in miR-17 HepG2 cells exacerbated steatotic change. Re-introduction of CYP7A1 into miR-17 HepG2 cell partially alleviated steatosis. CONCLUSIONS: miR-17 is a novel regulator of CYP7A1 signaling in hepatic lipid metabolism, suggesting a potential therapeutic approach for fatty liver.