Radiomic biomarkers for platinum-refractory head and neck cancer in the era of immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

Correlation between coronary heart disease severity and subsequent chronic rhinosinusitis severity: A retrospective cohort study.

Coronary heart disease (CHD) is associated with the development of several diseases. This retrospective population-based cohort study investigated the association between CHD severity and subsequent chronic rhinosinusitis (CRS) of varying severity. We used data from Taiwan's National Health Insurance Research Database. CHD was categorized as severe if treated using a coronary artery bypass graft (CABG) and as mild if treated with percutaneous coronary intervention (PCI). The primary outcome of this study was the development of CRS or severe CRS treated using functional endoscopic sinus surgery. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CRS and severe CRS in different patient groups. We included 31,784 patients who received PCI surgery (the CHD-PCI group) and 15,892 patients who received CABG surgery (the CHD-CABG group). A total of 813 and 482 episodes of CRS occurred in the CHD-PCI and CHD-CABG groups, respectively, and 45 and 16 severe CRS events occurred in the CHD-PCI and CHD-CABG groups, respectively. Our multivariable analysis demonstrated that the incidence of CRS in the CHD-CABG group was significantly higher than that in the CHD-PCI group (aHR: 1.196, 95% CI: 1.064-1.280, P = 0.0402), but the two groups had similar incidence rates of severe CRS (aHR: 0.795, 95% CI: 0.456-1.388, P = 0.5534). Subgroup analyses revealed that the association between CHD severity and CRS development was more significant among men (P = 0.0016). In conclusion, we determined that severe CHD treated with CABG was associated with a higher incidence of subsequent CRS, and this association was more prominent among men.

Association of the nasopharyngeal carcinoma and the subsequent open glaucoma development: a nationwide cohort study.

This study aimed to investigate the possible association between nasopharyngeal carcinoma (NPC) and following open angle glaucoma (OAG). A retrospective research applying the National Health Insurance Research Database (NHIRD) of Taiwan was conducted with a follow up period from January 1, 2000 to December 31, 2016. There were 4184 and 16736 participants that selected and categorized into the NPC and non-NPC groups after exclusion. The major outcome of our study was the development of OAG according to diagnostic codes, exam and managements. The Cox proportional hazard regression was employed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the two groups. In this study, a numbers of 151 and 513 OAG episodes occurred in the NPC and non-NPC groups and the NPC population showed a significantly higher incidence of OAG compared to the non-NPC population in multivariable analysis (aHR: 1.293, 95% CI: 1.077-1.551, p = 0.0057). Besides, the cumulative probability of OAG was significantly higher in the NPC group than that in the non-NPC population (p = 0.0041). About other risk factor for OAG, age older than 40 years old, diabetes mellitus and persistent steroid usage were related to OAG occurrence (all p < 0.05). In conclusion, the NPC may be an independent risk factor of following OAG development.

EF-24, a Curcumin Analog, Inhibits Cancer Cell Invasion in Human Nasopharyngeal Carcinoma through Transcriptional Suppression of Matrix Metalloproteinase-9 Gene Expression.

Cancer metastasis is a main cause of failure in treating subjects with nasopharyngeal carcinoma (NPC) and is frequently linked to high death rates. EF-24, an analog of curcumin, has exhibited many anti-cancer properties and enhanced bioavailability over curcumin. Nevertheless, the effects of EF-24 on the invasiveness of NPC are poorly understood. In this study, we demonstrated that EF-24 effectively inhibited TPA-induced motility and invasion responses of human NPC cells but elicited very limited cytotoxicity. In addition, the TPA-induced activity and expression of matrix metalloproteinase-9 (MMP-9), a crucial mediator of cancer dissemination, were found to be reduced in EF-24-treated cells. Our reporter assays revealed that such a reduction in MMP-9 expression by EF-24 was transcriptionally mediated by NF-κB via impeding its nuclear translocation. Further chromatin immunoprecipitation assays displayed that the EF-24 treatment decreased the TPA-induced interaction of NF-κB with the MMP-9 promoter in NPC cells. Moreover, EF-24 inhibited the activation of JNK in TPA-treated NPC cells, and the treatment of EF-24 together with a JNK inhibitor showed a synergistic effect on suppressing TPA-induced invasion responses and MMP-9 activities in NPC cells. Taken together, our data demonstrated that EF-24 restrained the invasiveness of NPC cells through the transcriptional suppression of MMP-9 gene expression, implicating the usefulness of curcumin or its analogs in controlling the spread of NPC.

Microbiota dysbiosis in odontogenic rhinosinusitis and its association with anaerobic bacteria.

Odontogenic rhinosinusitis is a subtype of rhinosinusitis associated with dental infection or dental procedures and has special bacteriologic features. Previous research on the bacteriologic features of odontogenic rhinosinusitis has mainly used culture-dependent methods. The variation of microbiota between odontogenic and nonodontogenic rhinosinusitis as well as the interplay between the involved bacteria have not been explored. Therefore, we enrolled eight odontogenic rhinosinusitis cases and twenty nonodontogenic rhinosinusitis cases to analyze bacterial microbiota through 16S rRNA sequencing. Significant differences were revealed by the Shannon diversity index (Wilcoxon test p = 0.0003) and PERMANOVA test based on weighted UniFrac distance (Wilcoxon test p = 0.001) between odontogenic and nonodontogenic samples. Anaerobic bacteria such as Porphyromonas, Fusobacterium, and Prevotella were significantly dominant in the odontogenic rhinosinusitis group. Remarkably, a correlation between different bacteria was also revealed by Pearson's correlation. Staphylococcus was highly positively associated with Corynebacterium, whereas Fusobacterium was highly negatively correlated with Prophyromonas. According to our results, the microbiota in odontogenic rhinosinusitis, predominantly anaerobic bacteria, was significantly different from that in nonodontogenic rhinosinusitis, and the interplay between specific bacteria may a major cause of this subtype of rhinosinusitis.

Lipocalin 2 Reduces MET Levels by Inhibiting MEK/ERK Signaling to Inhibit Nasopharyngeal Carcinoma Cell Migration.

Nasopharyngeal carcinoma (NPC) is the most common cancer that occurs in the nasopharynx, and it is difficult to detect early. The main cause of death of NPC patients is cancer metastasis. Lipocalin 2 (LCN2) has been shown to be involved in a variety of carcinogenesis processes. Here, we aimed to study the role of LCN2 in NPC cells and determine its underlying mechanism. We found that LCN2 was expressed differently in NPC cell lines, namely HONE-1, NPC-39, and NPC-BM. The down-regulation of LCN2 levels by siRNA targeting LCN2 (siLCN2) increased cell migration and invasion in HONE-1 cells, while the up-regulation of LCN2 levels by transfection with the LCN2 expression plasmid decreased cell migration and invasion in NPC-BM cells. Furthermore, LCN2 levels negatively regulated the phosphorylation of MEK/ERK pathways. The treatment of the specific MEK/ERK inhibitor, U0126, reduced cell migration in HONE-1 cells, whereas the treatment of tBHQ, an ERK activator, enhanced cell migration in NPC-BM cells. Based on the bioinformatics data, there was a moderately negative correlation between LCN2 and MET in metastatic NPC tissues (r = -0.5946, p = 0.0022). Indeed, the manipulation of LCN2 levels negatively regulated MET levels in these NPC cells. The treatment of U0126 reduced siLCN2-increased MET levels, while the treatment of tBHQ enhanced LCN2-enhanced MET levels. Interestingly, the down-regulation of MET levels by siMET further decreased siLCN2-enhanced MET levels and cell migration. Therefore, LCN2 inhibits NPC cell migration by reducing MET levels through MEK/ERK signaling.

Preoperative prediction model to evaluate salvage surgery in patients with recurrent or second primary oral cavity squamous cell carcinoma.

OBJECTIVE: In approximately 50% of patients with oral cavity squamous cell carcinoma (OCSCC), the disease progresses after curative surgery. However, the role of salvage surgery (SS) is controversial, and life expectancy after SS is unknown. METHODS: In this study, 262 patients with OCSCC with locoregional recurrence and second primary OCSCC were retrospectively enrolled and divided into a resectable (55.0%, 144/262) and unresectable (45.0%, 118/262) groups. After excluding neck recurrence only, SS had been performed 195 times in the resectable group. The corresponding preoperative clinicopathologic factors and postsurgery survival (PSS) of each SS were pooled for analysis. RESULTS: Median survival after disease progression was 64.2 and 10.4 months for the resectable and unresectable groups, respectively. In the resectable group, one-fifth (19.5%, 37/190) of the patients died within 1 year of SS (PSS < 1 year), and one-third (32.8%, 64/195) of the patients had undergone SS two or more times. The interval from the last surgery ≤ 12 months, depth of invasion of the last surgery > 1 cm, and clinical evidence of nodal disease at the preoperative evaluation were independent predictors of poor PSS. A scoring prediction model was established with 1 point for each factor. The results revealed 1-year postsurgery death rates of 10.3% in the low-risk group (score: 0-1) and 48.6% in the high-risk group (score: 2 or 3) (P < 0.001). CONCLUSIONS: In conclusion, an effective scoring model predicting life expectancy after SS for patients with OCSCC was established.

Dihydromyricetin inhibits cancer cell migration and matrix metalloproteinases-2 expression in human nasopharyngeal carcinoma through extracellular signal-regulated kinase signaling pathway.

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.

Risk of head and neck cancer in patients with peptic ulcers and the effect of Helicobacter pylori treatment.

It remained inconclusive whether patients with peptic ulcer disease had a higher risk of head and neck cancer (HNC). Therefore, we enrolled 109,360 patients with peptic ulcer disease and matched for age and sex with 218,720 controls from the Taiwan National Health Insurance Research Database between January 1, 1997 and December 31, 2013.The HNC incidence rate was 1.33-fold higher in the peptic ulcer group than in the control group (7.52 vs. 5.68 per 100,00 person-years; crude relative risk: 1.33; 95% confidence interval [CI]: 1.08-1.63) after > 6 years of follow-up. However, in the peptic ulcer subgroup with H. pylori treatment, HNC risk was not significantly different from that of the control group (crude relative risk: 1.12; 95% CI: 0.86-1.46). Moreover, the population with peptic ulcers had the highest risk of laryngeal and hypopharyngeal cancer (adjusted HR: 2.27 [95% CI: 1.16-4.44] and 2.00 [95% CI, 1.13-3.55]), respectively. This observational study suggested that peptic ulcer disease is associated with an increased incidence of laryngeal and hypopharyngeal cancer and H. pylori treatment may have a role in preventing HNC in patients with peptic ulcer disease.

Prediction Model of Distant Metastasis in Oral Cavity Squamous Cell Carcinoma With or Without Regional Lymphatic Metastasis.

Patients with oral cavity squamous cell carcinoma (OCSCC) who develop distant metastasis (DM) face poor outcomes, and effective prediction models of DM are rare. A total of 595 patients with OCSCC were retrospectively enrolled in this study. Because pathological N staging significantly influences the development and mechanisms of DM, the patients were divided into nodal-negative (pN-) and -positive (pN+) groups. Clinical outcomes, prognoses, and prediction models were analyzed separately for both groups. Overall, 8.9% (53/595) of these patients developed DM. Among the DM cases, 84.9% (45/53) of them developed DM within the first 3 years. The median overall survival, locoregional recurrence-free survival, time until DM development, and postmetastatic survival were 19.8, 12.7, 14.6, and 4.1 months, respectively. Distinguishing patients who only developed locoregional recurrence from those with DM according to locoregional conditions was difficult. Age, surgical margin, and early locoregional recurrence were predictors of DM that were independent of time until DM in the pN- group; the lymphocyte-to-monocyte ratio, presence of lymphovascular invasion, and early locoregional recurrence in the pN+ group were determined. If one point was scored for each factor, then two scoring systems were used to classify the patients into low- (score = 0), intermittent- (score = 1), or high- (score = 2 or 3) risk for the pN- and pN+ groups. According to this scoring system, the 3-year DM rates for the low, intermittent, and high risk subgroups were 0.0%, 5.9%, and 17.8% for the pN- group and 7.1%, 44.9%, and 82.5% for the pN+ group, respectively. These systems also effectively predicted DM, and the areas under the curve predicted DM occurring within the first 3 years were 0.744 and 0.820 for the pN- and pN+ groups, respectively. In conclusion, effective scoring models were established for predicting DM.

Predictors of early progression after curative resection followed by platinum-based adjuvant chemoradiotherapy in oral cavity squamous cell carcinoma.

OBJECTIVES: Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown. METHODS: In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical-pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for DFIs. Survival was estimated using the Kaplan-Meier method and log-rank tests, and a scoring system for predicting early progression was established. RESULTS: One-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0-1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or <2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively. CONCLUSIONS: The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC.

Tricetin Suppresses Migration and Presenilin-1 Expression of Nasopharyngeal Carcinoma through Akt/GSK-3ß Pathway.

Lymph node migration results in poor prognoses for nasopharyngeal carcinoma (NPC) patients. Tricetin, a flavonoid derivative, regulates tumorigenesis activity through its antiproliferative and antimetastatic properties. However, the molecular mechanism of tricetin affecting the migration and invasion of NPC cells remains poorly understood. In this paper, we examined the antimetastatic properties of tricetin in human NPC cells. Our results demonstrated that tricetin at noncytotoxic concentrations (0-80 3M) noticeably reduced the migration and invasion of NPC cells (HONE-1, NPC-39, and NPC-BM). Moreover, tricetin suppressed the indicative protease, presenilin-1 (PS-1), as indicated by protease array. PS-1 was transcriptionally inhibited via the Akt signaling pathway but not mitogen-activated protein kinase pathways, such as the JNK, p38, and ERK1/2 pathways. In addition to upregulating GSK-3[Formula: see text] phosphorylation through Akt suppression, tricetin may downregulate the activity of PS-1. Overall, our study provides new insight into the role of tricetin-induced molecular regulation in the suppression of NPC metastasis and suggests that tricetin has prospective therapeutic applications for patients with NPC.

Chronic rhinosinusitis after radiotherapy in patients with head and neck cancer: a population-based cohort study in Taiwan.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common post-radiotherapy (RT) side effect in patients with nasopharyngeal cancer (NPC). However, whether RT is a risk factor for CRS in patients with other types of head and neck cancer remains unclear. This study investigated the association, if any, between CRS and RT in patients with head and neck cancer. METHODS: This retrospective cohort study included the data of patients newly diagnosed as having head and neck cancer between January 1, 2005, and December 31, 2008, from the 2005 Longitudinal Health Insurance Database. Patients were categorized into the following groups according to the treatment regimens received: RT alone (RT-alone), RT combined with other treatments (any-RT), and treatments without RT (no-RT). The outcome was the occurrence of CRS after treatment. RESULTS: Of the 701 patients, 7% experienced CRS within 5 years after initial treatment. Patients were divided into subgroups according to different treatment policies, and the RT-alone group, any-RT group, and no-RT group had 5-year incidence of CRS of 12%, 9.3%, and 4.5%, respectively. Patients in the RT-alone and any-RT groups exhibited an increased risk of CRS compared with patients in the no-RT group (hazard ratio: 6.76 and 2.91; 95% confidence interval: 2.60 to 17.5 and 1.60 to 5.31, respectively). CONCLUSION: This is the first nationwide population-based cohort study to evaluate the risk of posttreatment CRS in patients with head and neck cancer. Our findings indicate that RT is a major risk factor for CRS. Thus, physicians should consider this potential risk in patients with head and neck cancer after RT.

Microbiota Dysbiosis in Fungal Rhinosinusitis.

Fungal rhinosinusitis is a unique phenotype of chronic rhinosinusitis with unique clinical and histological characteristics. The role of bacterial microbiota in various phenotypes chronic rhinosinusitis is not thoroughly understood. Therefore, we conducted 16s rRNA amplification sequencing to determine differences in bacterial communities between phenotypes (fungal vs. non- fungal) and anatomical sites (middle meatus vs. nasopharynx). Endoscope-guided swabs were used to collect samples from the middle meatus and nasopharynx of seven consecutive patients with fungal and 18 consecutive patients with non-fungal rhinosinusitis. DNA was extracted and investigated through 16S rRNA amplification. Among samples from the middle meatus, Shannon diversity was significantly lower in those from the fungal rhinosinusitis group (p = 0.029). However, no significant differences in diversity were noted between nasopharynx samples (p = 0.85). Fungal rhinosinusitis samples exhibited a distinct distribution of taxon relative abundance, which involved not only the absence of rhinosinusitis-associated commensal Corynebacterium and Fusobacterium in the middle meatus but also a significant increase in Haemophilus prevalence and abundance. This is the first study to compare bacterial communities in fungal and non-fungal rhinosinusitis samples. Our findings demonstrated that bacterial community dysbiosis was more apparent in fungal rhinosinusitis samples and was limited to the middle meatus.

Epigallocatechin-3-gallate inhibits migration of human nasopharyngeal carcinoma cells by repressing MMP-2 expression.

Metastasis of the cancer cells to the regional lymph nodes parts of the body remains an important cause of treatment failure in nasopharyngeal carcinoma (NPC) patients. Epigallocatechin-3-gallate (EGCG), the most important ingredient in the green tea, has been reported to possess antioxidant and anticancer activities. However, the effects of EGCG on NPC cell metastasis are still unclear. In the present study, we examined the in vitro antimetastatic properties of EGCG on human NPC cells, NPC-39, HONE-1 and NPC-BM. The results revealed that EGCG considerably inhibited the migration abilities of three NPC cells. The matrix metalloproteinases-2 (MMP-2) activity and expression were also significantly inhibited by EGCG treatment. Furthermore, EGCG suppressed the phosphorylation of the Src signaling pathway. Moreover, blocking the Src pathway also inhibits MMP-2 expression and migration in the NPC cells. In conclusion, this study revealed that EGCG could inhibit the metastatic activity of human NPC cells by downregulating the protein expression of MMP-2 through modulation of the Src signaling pathway, suggesting that EGCG may be a potential candidate for chemoprevention of NPC.

Licochalcone A induces apoptotic cell death via JNK/p38 activation in human nasopharyngeal carcinoma cells.

Licochalcone A is widely studied in different fields and possesses antiasthmatic, antibacterial, anti-inflammatory, antioxidative, and anticancer properties. Its antimalignancy activity on renal, liver, lung, and oral cancer has been explored. However, limited studies have been conducted on the inhibitory effects of licochalcone A in human nasopharyngeal carcinoma cells. We determined cell viability using MTT assay. Cell cycle distribution and apoptotic cell death were measured via flow cytometry. Caspase activation and mitogen-activated protein kinase-related proteins in nasopharyngeal cancer cells in response to licochalcone A were identified by Western blot analysis. Results indicated that licochalcone A reduces cell viability and induces apoptosis, as evidenced by the upregulation of caspase-8 and caspase-9, caspase-3 activation, and cleaved-poly ADP-ribose polymerase expression. Treatment with licochalcone A significantly increases ERK1/2, p38, and JNK1/2 activation. Co-administration of a JNK inhibitor (JNK-IN-8) or p38 inhibitor (SB203580) abolishes the activation of caspase-9, caspase-8, and caspase-3 protein expression during licochalcone A treatment. These findings indicate that licochalcone A exerts a cytostatic effect through apoptosis by targeting the JNK/p38 pathway in human nasopharyngeal carcinoma cells. Therefore, licochalcone A is a promising therapeutic agent for the treatment of human nasopharyngeal cancer cells.

Bacterial alterations in salivary microbiota and their association in oral cancer.

Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity and the fourth leading malignancy and cause of cancer-related death in the male population of Taiwan. Most cases are detected at advanced stages, resulting in poor prognosis. Therefore, improved detection of early oral health disorders is indispensable. The involvement of oral bacteria in inflammation and their association with OSCC progression provide a feasible target for diagnosis. Due to the nature of oral neoplasms, the diagnosis of epithelial precursor lesions is relatively easy compared with that of other types of cancer. However, the transition from an epithelial precursor lesion to cancer is slow and requires further and continuous follow-up. In this study, we investigated microbiota differences between normal individuals, epithelial precursor lesion patients, and cancer patients with different lifestyle habits, such as betel chewing and smoking, using next-generation sequencing. Overall, the oral microbiome compositions of five genera, Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia, revealed significant differences between epithelial precursor lesion and cancer patients and correlated with their classification into two clusters. These composition changes might have the potential to constitute a biomarker to help in monitoring the oral carcinogenesis transition from epithelial precursor lesion to cancer.

Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

MMP-11 promoted the oral cancer migration and Fak/Src activation.

Matrix metalloproteinase-11 (MMP-11) has been observed in most invasive human carcinomas. The current study investigated the association between the clinicopathological characteristics and MMP-11 expression in oral squamous cell carcinoma (OSCC) patients. Immunohistochemistry (IHC) staining was performed to assess MMP-11 expression in 279 patients with OSCC. In addition, the metastatic effects of the MMP-11 overexpression on the OSCC cells were also investigated. We found that MMP-11 expression was present in 118/279 (42.3%) cases and expression of MMP-11 was associated with higher incidence of lymph node metastasis and worse grade of tumor differentiation. Importantly, OSCC patients with strong expression of MMP-11 had a significantly lower survival rate (p=0.010). Furthermore, MMP-11 overexpression in OSCC cells increased in vitro cell migration. Mechanistically, MMP-11 increased the cell motility of OSCC cells through focal adhesion kinase/Src kinase (FAK/Src) pathway. In conclusion, our results revealed that the MMP-11 expression in OSCC samples can predict the progression, especially lymph node metastasis, and the survival of OSCC patients in Taiwan.