Tetrastigma hemsleyanum polysaccharide ameliorates cytokine storm syndrome via the IFN-γ-JAK2/STAT pathway.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an disease characterized by pulmonary edema and widespread inflammation, leading to a notably high mortality rate. The dysregulation of both pro-inflammatory and anti-inflammatory systems, results in cytokine storm (CS), is intricately associated with the development of ALI/ARDS. Tetrastigma hemsleyanum polysaccharide (THP) exerts remarkable anti-inflammatory and immunomodulatory effects against the disease, although its precise role in pathogenesis remains unclear. In the present study, an ALI/ARDS model was established using bacterial lipopolysaccharides. THP administration via aerosol inhalation significantly mitigated lung injury, reduced the number of inflammatory cells, and ameliorated glycerophospholipid metabolism. Furthermore, specific CS-related pathways were investigated by examining the synergy between tumor necrosis factor-α and interferon-γ used to establish CS models. The results indicated that THP effectively decreased inflammatory damage and cell death. The RNA sequencing revealed the involvement of the Janus kinase (JAK) 2-signal transducers and activators of transcription (STAT) signaling pathway in exerting the mentioned effects. Additionally, THP inhibited the activation of the JAK-STAT pathway, thereby alleviating the CS both in vivo and in vitro. Overall, THP exhibited marked therapeutic potential against ALI/ARDS and CS, primarily by targeting the IFN-γ-JAK2/STAT signaling pathway.

Tetrastigma hemsleyanum polysaccharide ameliorated ulcerative colitis by remodeling intestinal mucosal barrier function via regulating the SOCS1/JAK2/STAT3 pathway.

Ulcerative colitis (UC) is characterized by a chronic and protracted course and often leads to a poor prognosis. Patients with this condition often experience postoperative complications, further complicating the management of their condition. Tetrastigma hemsleyanum polysaccharide (THP) has demonstrated considerable potential as a treatment for inflammatory bowel disease. However, its underlying mechanism in the treatment of UC remains unclear. This study systematically and comprehensively investigated the effects of THP on dextran sulfate-induced UC mice and illustrated its specific mechanism of action. The colon and spleen in UC mice were restored after THP treatment. The levels of key markers, such as secretory immunoglobulin A, ß-defensin, and mucin-2 were increased, collagen deposition and epithelial cell apoptosis were decreased. Notably, THP administration led to increased levels of Ki67 and tight junction proteins in colon tissue and reduced colon tissue permeability. THP contributed to the restored balance of intestinal flora. Furthermore, THP downregulated the expressions of the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17 and promoted those of the regulatory factors forkhead box protein P3. It also exerted anti-inflammatory effects by promoting suppressor of cytokine signaling (SOCS1) expression and inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results demonstrated that THP had an efficacy comparable to that of JAK inhibitor in treating UC. In addition, THP might play a role in UC therapy through modulation of the SOCS1/JAK2/STAT3 signaling pathway and remodeling of the intestinal mucosal barrier.

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.

Antipyretic effect of inhaled Tetrastigma hemsleyanum polysaccharide on substance and energy metabolism in yeast-induced pyrexia mice via TLR4/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.

Ameliorating role of Tetrastigma hemsleyanum polysaccharides in antibiotic-induced intestinal mucosal barrier dysfunction in mice based on microbiome and metabolome analyses.

The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and maintains intestinal homeostasis. The possible mechanisms were related to sphingolipid metabolism, linoleic acid metabolism, and D-glutamine and D-glutamate metabolism. Our results demonstrated the potential therapeutic effect of THP against intestinal flora disorders and intestinal barrier function impairment caused by antibiotics.

Coelonin protects against PM2 .5 -induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro.

One of the important monitoring indicators of the air pollution is atmospheric fine particulate matter (PM2.5 ), which can induce lung inflammation after inhalation. Coelonin can alleviate PM2.5 -induced macrophage damage through anti-inflammation. However, its molecular mechanism remains unclear. We hypothesized that macrophage damage may involve the release of inflammatory cytokines, activation of inflammatory pathways, and pyrosis induced by inflammasome. In this study, we evaluated the anti-inflammation activity of coelonin in PM2.5 -induced macrophage and its mechanism of action. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured by NO Assay kit and dichlorofluorescein-diacetate (DCFH-DA), and apoptosis were measured by Flow cytometry and TUNEL staining. The concentration of inflammatory cytokines production was measured with cytometric bead arrays and ELISA kits. The activation of NF-κB signaling pathway and NLRP3 inflammasome were measured by immunofluorescence, quantitative reverse transcription-polymerase chain reaction and western blot. As expected, coelonin pretreatment reduced NO production significantly as well as alleviated cell damage by decreasing ROS and apoptosis. It decreased generation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in PM2.5 -induced RAW264.7 and J774A.1 cells. Moreover, coelonin markedly inhibited upregulating the expression of toll-like receptor (TLR)4 and cyclo-oxygenase (COX)-2, blocked activation of p-nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed expression of NLRP3 inflammasome, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, the results showed that coelonin could protect against PM2.5 -induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro.

Association between serum arsenic and oral cancer risk: A case-control study in southeast China.

OBJECTIVES: Evidence on serum arsenic and oral cancer risk was limited. We aimed to evaluate the association between serum arsenic and the risk of oral cancer in a southeast China population. METHODS: Serum arsenic was determined for 325 oral cancer patients and 648 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Logistic regression and restricted cubic spline were analysed the association between serum arsenic level and oral cancer risk, and crude and adjusted odds ratios (aOR) with 95% confidence interval (95% CI) were calculated. Factors adjusted for included age, gender, BMI, smoking, drinking, education, residence, marital status and dietary factors. Stratification analysis was further performed according to drinking, smoking and dietary characteristics. RESULTS: Serum arsenic level was lower in the case group (P50  = 19.2µg/L, IQR = 11.6 ~ 26.4µg/L) than in the control group (P50  = 30.2 µg/L, IQR = 25.0 ~ 36.4 µg/L). An inverse but nonlinear association was observed between arsenic level and oral cancer risk by restricted cubic spline. These with moderate serum arsenic levels had a lower risk of oral cancer than those with low levels (OR = 0.11; 95%CI: 0.07-0.18), after adjusting for demographic and dietary intake factors. We also kept serum arsenic as a continuous variable in a regression model, where a similar inverse association between arsenic and oral cancer was observed, with OR = 0.86 (95%CI: 0.84-0.88). Stratification analysis revealed no significant multiplicative interactions between serum arsenic and smoking, drinking or dietary intake. CONCLUSION: Serum arsenic is inversely related to oral cancer risk. Relative to those with low levels of arsenic, people with moderate serum arsenic levels had a lower risk of oral cancer. If confirmed, serum arsenic level may be a useful predictive marker for oral cancer risk.

[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.

Prognostic value of preoperative systemic inflammation response index in patients with oral squamous cell carcinoma: Propensity score-based analysis.

BACKGROUND: The aim of the study was to elucidate the relationship between systemic inflammation response index (SIRI) and the prognosis of postoperative oral squamous cell carcinoma (OSCC) patients. METHODS: The prognostic value of SIRI was evaluated in a prospective cohort consisting of 535 OSCC patients with surgical resection. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses were used to further verify the prognostic value of SIRI. RESULTS: Patients with a higher SIRI had a significantly increased risk of mortality compared with those with a low SIRI (HR [hazard ratio]: 1.60, 95% CI [confidence interval]: 1.04-2.47). The similar association pattern was observed following PSM (HR: 1.97, 95% CI: 1.14-3.40) and IPTW (HR: 1.70, 95% CI: 1.29-2.24) analyses. Of note, receiving postoperative chemotherapy resulted in a 72% of decreased risk of death among patients with a higher SIRI (HR: 0.28, 95% CI: 0.08-0.95). Additionally, a novel prognostic nomogram, based on TNM stage, tumor differentiation, and SIRI, demonstrated superior accuracy for the prediction of overall survival than that of the seventh edition of the AJCC staging system. CONCLUSION: Preoperative SIRI may be a valuable tool for prediction of survival of OSCC patients.

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.

Dynamic evaluation of conditional survival in patients with oral squamous cell carcinoma after surgical resection: A large-scale prospective study.

OBJECTIVE: To dynamically estimate conditional survival (CS) probabilities for patients with oral squamous cell carcinoma (OSCC) after surgical resection. METHOD: A large-scale prospective study was performed involving 1147 eligible OSCC patients from December 2002 to June 2018. Follow-up was completed on January 8, 2019. Cox proportional hazards models were utilized to assess prognostic factors related to overall survival (OS). Three-year CS (CS3) of patients who had already survived x years was calculated as the formula CS3 = OS(x+3)/OS(x). RESULTS: CS3 estimates at the time of 0, 1, 3, 5-year survival demonstrated a tendency increase over time, and improved from 78.47% to 82.25%, while the postoperative actuarial OS decreased from 78.47% at 3 years to 57.12% at 8 years. Moreover, the differences between CS3 and actuarial OS were more obvious among patients with unfavorable tumor characteristics. Disparities in CS3 across all subgroups of tumor features illustrated more prominent at baseline (d range: 0.24 to 0.40), while the gaps would narrow if those patients have already survived 5 years (d range: -0.01 to 0.18). CONCLUSION: Our findings suggest that survival profiles of OSCC patients evolve and increase over time following resection, especially for those with unfavorable tumor features at initial diagnosis. CS estimates may provide more accurate prediction and guide surveillance schedules.

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.

Propensity score analysis exploring the impact of smoking and drinking on the prognosis of patients with oral cancer.

BACKGROUND: To explore the effect of smoking and drinking on survival of patients with oral cancer by comparing the characteristics and survival of nonsmoking and nondrinking (NSND) patients in contrast to smoking and/or drinking (SD) patients. METHODS: This prospective study including 1165 patients with oral cancer was conducted in Fujian, China from January 2005 to January 2019. The patients were categorized to two groups, the NSND group and SD group. We compared overall survival and disease-specific survival between the two groups using the Kaplan-Meier method and Cox proportional hazards regression before and after propensity score matching (PSM) to explore the effect of smoking and drinking on the prognosis of patients with oral cancer. RESULTS: NSND patients accounted for 55.45% (646 patients) of all the patients with oral cancer. SD patients with oral cancer tended to be older and mainly are male (98.46%) and with more advanced disease status. There are trends toward both higher risk of all-cause death (HR = 1.678; 95% CI: 1.086-2.594) and oral cancer specific death (HR = 1.632; 95% CI: 1.044-2.552) in SD patients with oral cancer before PSM. After PSM, the association is still significant, with adjusted HR of 1.897 (95% CI: 1.138-3.165) for all-cause death and adjusted HR of 1.764 (95% CI: 1.043-2.983) for oral cancer-specific death. Additionally, PSM can improve the HR value and result in a stronger association. CONCLUSIONS: Social and clinical characteristics of NSND patients differed from SD patients with oral cancer. SD patients with oral cancer have higher all-cause mortality and oral cancer-specific mortality than NSND patients.

Association between dietary inflammatory index and the risk of oral cancer in the southeast of China.

BACKGROUND/OBJECTIVES: To evaluate the role of the potential inflammatory effects of diet using the Energy adjusted Dietary Inflammatory Index (E-DII) for oral cancer. SUBJECTS/METHODS: A case-control study including 295 oral cancer cases and 425 controls from September 2010 to June 2018 was performed in Fujian Province, China. The E-DII was calculated based on the food frequency questionnaire (FFQ) and adjusted by total energy intake. The association between E-DII and the risk of oral cancer was estimated with unconditional logistic regression model. RESULTS: Compared with E-DII score in the lowest quartile, those with E-DII score in the fourth quartile were at the higher risk of oral cancer (OR = 2.57; 95% CI: 1.54, 4.29, Ptrend = 0.013). When analyses were carried out using E-DII as a continuous variable, one-unit increase in E-DII increased the odds of having oral cancer by 3% (95% CI: 1.00, 1.06). Moreover, there was a significant interaction between the E-DII and oral hygiene for oral cancer (Pinteraction < 0.001, in those without and with poor hygiene, the OR (95% CI) were 1.96 (0.96, 4.00) and 4.23 (1.83, 9.81), respectively). CONCLUSIONS: The present study suggests that the higher E-DII score, indicated a pro-inflammatory diet, may be a risk factor for oral cancer in southeast of China. More large samples and prospective studies need to validate our results and explore the prevention strategies of oral cancer via changing dietary habits.

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.

Log Odds of Positive Lymph Nodes is Not Superior to the Number of Positive Lymph Nodes in Predicting Overall Survival in Patients With Oral Squamous Cell Carcinomas.

PURPOSE: It is unclear whether the log odds of positive lymph nodes (LODDS) outperforms the number of positive lymph nodes (LN+) in predicting the overall survival (OS) of oral squamous cell carcinoma (OSCC) patients. The specific aim of this study was to compare the prognostic predictive performance of LN+ with LODDS in OSCC patients. MATERIALS AND METHODS: This prospective cohort study was conducted in Fujian, China, from December 2005 to January 2017. Patients' characteristics and clinicopathologic data were obtained through medical records, and follow-up data were obtained by telephone interviews. Cox proportional hazards models were used to evaluate the association between LN+ or LODDS and OS in OSCC. Finally, the Harrell concordance index, Akaike information criterion, and area under the receiver operating characteristic curve were adopted as criteria for assessing the predictive performance of lymph node models. RESULTS: For all 706 patients, the 5-year survival rate was 65.69% (95% confidence interval, 0.61 to 0.70) and the mean age at diagnosis was 57.32 ± 11.80 years. Of the patients, 456 were men and 250 were women (ratio of 1.82:1). LN+ and LODDS were significantly associated with a poor prognosis of OSCC patients (all P values for trend < .001). Furthermore, the prognostic value of LODDS was not better than that of LN+. An interesting finding was that there was a J-shaped relationship between the number of negative lymph nodes and OS. The hazard ratio was reduced with each additional negative lymph node dissected up to 24 negative lymph nodes, with no improvement in prognosis beyond this number. Moreover, when the number of negative lymph nodes was greater than 40, the negative lymph nodes suggested a worse prognosis for OSCC patients. CONCLUSIONS: Our study suggests that the discriminatory capability of LODDS was not superior to that of LN+. An interesting finding was that, when the number of negative lymph nodes was greater than 40, the predictive power of LODDS was reduced tremendously.

Upregulated long noncoding RNA ENST00000470447.1 inhibits cell migration and invasion and predicts better disease-free survival of oral cancer.

BACKGROUND: The aim of the present study was to assess the long noncoding RNA (lncRNA) expression profile of oral cancer and clarify the biological functions and clinical value of a novel lncRNA ENST00000470447.1. METHOD: Microarray assay was used to explore lncRNA expression profiles in three paired oral cancer and adjacent normal tissue samples. The expression of targeted lncRNA (ENST00000545372.1, ENST00000470447.1, and ENST00000412353.1) was validated by quantitative real-time polymerase chain reaction. Then we evaluated the biological and clinical roles of ENST00000470447.1 in oral cancer by in vitro assays and multivariable Cox regression analysis. RESULTS: LncRNAs were aberrantly expressed in oral cancer tissues. The expression levels of ENST00000470447.1 and ENST00000412353.1 in oral cancer tissues were significantly lower than those in matched adjacent noncancerous tissues (P < .001). in vitro assays indicated that overexpression of ENST00000470447.1 significantly inhibited the proliferation, migration, and invasion ability of Tca-8113 cells, whereas promoted the apoptosis of Tca-8113 cells. Furthermore, ENST00000470447.1 expression was significantly correlated with tumor differentiation (P = .030). Cox regression analyses demonstrated that high ENST00000470447.1 expression was associated with better disease-free survival for patients with oral cancer (hazard ratio: 0.25, 95% CI: 0.06-0.95; P = .041). CONCLUSION: Our findings suggest that ENST00000470447.1 can be served as a potential novel marker for recurrence and metastasis prediction of patients with oral cancer, which may provide a potential therapeutic target for oral cancer.

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.

Three prognostic indexes as predictors of response to adjuvant chemoradiotherapy in patients with oral squamous cell carcinoma after radical surgery: A large-scale prospective study.

BACKGROUND: To develop and validate practical prognostic indexes (PIs) for predicting the prognosis and response to postoperative adjuvant therapy in patients with oral squamous cell carcinoma (OSCC). METHODS: A large cohort of 1071 OSCC patients were randomized to either training set (N = 708) or validation set (N = 363). Three types of PIs were developed according to the nomogram scores, ß coefficients and excess hazard ratios, respectively. Restricted cubic spline was used to demonstrate the relationship between PIs and the risks of death. RESULTS: First, a nomogram was developed incorporating age at diagnosis, smoking status, clinical stage, tumor differentiation, lymph node status, comorbidity, and neutrophil to lymphocyte ratio levels. Then, three PIs were established with high survival predictive ability, and were superior to AJCC staging system (all P < .05). The risks of death were escalated continuously with the increasing number of PIs. Interestingly, adjuvant chemoradiotherapy was positively associated with poor overall survival in patients with low PIs, but exerted a beneficial effect on patients with high PIs. CONCLUSION: Combined nomogram with further established PIs not only predicts the survival probability of OSCC patients, but also continuously quantifies the risk of death. High PIs could predict a beneficial response to adjuvant chemoradiotherapy, whereas low PIs indicate an unfavorable response.

Nomograms and risk scores for predicting the risk of oral cancer in different sexes: a large-scale case-control study.

Background: Although previous studies have explored the associations of modifiable lifestyle factors with oral cancer risk, few studies integrated these factors and established predictive tools for oral cancer risk in different sexes. Methods: Using a case-control study design, a total of 978 oral cancer cases and 2646 healthy controls were recruited in this study. Nomograms were constructed according to significant factors in multivariable logistic regression. Risk scores were calculated based on the nomograms and quantified the risk of oral cancer using restricted cubic spline. Results: Multivariate analyses demonstrated that smoking, alcohol drinking, tea, intake of fish, seafood, vegetables, fruits, teeth loss, regular dental visits and repetitive dental ulcer were independent factors for male oral cancer. Passive smoking, age at first intercourse, cooking oil fumes exposure, tea, intake of beans, vegetables, fruits, teeth loss, regular dental visits and repetitive dental ulcer were associated with female oral cancer. Then, two nomograms were developed for predicting the probability of oral cancer in men and women with the C-index of 0.768 (95% CI: 0.723-0.813) and 0.700 (95% CI: 0.635-0.765), respectively. Restricted cubic splines graphically revealed the risk of oral cancer in individuals with different risk scores. Moreover, the risk escalated continuously with the increasing number of the risk scores among both sexes. Conclusions: Combining nomograms with risk scores developed in this study could precisely predict oral cancer occurrence and provide an accurate risk assessment.