GPRASP1 is a candidate anti-oncogene and correlates with immune microenvironment and immunotherapeutic efficiency in head and neck cancer.

BACKGROUND: G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) plays an important role in tumorigenesis. However, GPRASP1 specific role has not been clarified in head and neck cancer (HNC). METHODS: HNC RNA sequencing (RNA-seq) datasets, DNA methylation data, somatic mutation data, copy number variation (CNV) data, and corresponding clinicopathologic information were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive evaluation was performed to explore the relationship of GPRASP1 expression with clinicopathologic characteristics, CNV, and DNA methylation. Additionally, we employed HNC tissue microarray (TMA) to further confirm the relation between GPRASP1 expression and clinical features. Then, we systematically associated the GPRASP1 with immunological properties from numerous perspectives, such as immune cell infiltration, immune-related pathways, immune checkpoint inhibitors (ICIs), immunomodulators, immunogenicity, and immunotherapy. RESULTS: Analyzing TCGA, GEO, and TMA datasets, GPRASP1 is significantly down-regulated in HNC compared to normal tissues. The expression of GPRASP1 is significantly negatively correlated with clinical features (perineural invasion, histologic grade, T stage, and TNM stage), and is an independent predictor of favorable prognosis, regardless of other clinicopathological features (HR: 0.42, 95% CI 0.20-0.91, p = 0.028). The etiological investigation found that the abnormal expression of GPRASP1 was related to DNA methylation, not CMV. Subsequently, the high expression of GPRASP1 was significantly correlated with immune cell infiltration (CD8+  T cell, tumor infiltrating lymphocyte), immune-related pathways (cytolytic activity, check-point, human leukocyte antigen), ICIs (CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT), immunomodulators (CCR4/5, CXCL9, CXCR3/4/5), and immunogenicity (immune score, neoantigen, tumor mutation burden). Finally, immunophenoscore and tumor immune dysfunction and exclusion analysis demonstrated that GPRASP1 expression levels can accurately predict the immunotherapeutic response. CONCLUSION: GPRASP1 is a promising candidate biomarker that plays a role in the occurrence, development, and prognosis of HNC. Evaluating GPRASP1 expression will aid in the characterization of tumor microenvironment infiltration and orient more efficient immunotherapy strategies.

Genome-Wide Identification and Expression Analysis of C3H Zinc Finger Family in Potato (Solanum tuberosum L.).

Transcription factors containing a CCCH structure (C3H) play important roles in plant growth and development, and their stress response, but research on the C3H gene family in potato has not been reported yet. In this study, we used bioinformatics to identify 50 C3H genes in potato and named them StC3H-1 to StC3H-50 according to their location on chromosomes, and we analyzed their physical and chemical properties, chromosome location, phylogenetic relationship, gene structure, collinearity relationship, and cis-regulatory element. The gene expression pattern analysis showed that many StC3H genes are involved in potato growth and development, and their response to diverse environmental stresses. Furthermore, RT-qPCR data showed that the expression of many StC3H genes was induced by high temperatures, indicating that StC3H genes may play important roles in potato response to heat stress. In addition, Some StC3H genes were predominantly expressed in the stolon and developing tubers, suggesting that these StC3H genes may be involved in the regulation of tuber development. Together, these results provide new information on StC3H genes and will be helpful for further revealing the function of StC3H genes in the heat stress response and tuber development in potato.

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection.

PURPOSE: The aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples. METHODS: Samples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry. RESULTS: Five-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers. CONCLUSIONS: The 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.

Is there a higher prevalence of human papillomavirus infection in Chinese laryngeal cancer patients? A systematic review and meta-analysis.

Accumulating evidence suggests that persistent human papillomavirus (HPV) infection is closely related to the risk of certain types of head and neck squamous cell carcinoma types, including laryngeal cancer (LC). Some reports indicated a higher HPV prevalence in Chinese LC patients, which remains to be established due to small study sample sizes. The aim of this study was to estimate the HPV infection rate in Chinese LC patients and assess the LC risk conferred by high-risk subtype HPV infection by meta-analysis. We searched MEDLINE, the Embase Database, Chinese National Knowledge Infrastructure, Wanfang Database, and VIP Database for studies published in either English or Chinese up to October 2013, and systematically reviewed 28 original research articles that met the inclusion criteria. Both the HPV infection rate in the LC group (all 28 studies) and the LC risk from high-risk HPV infection (a subgroup of 12 case-control studies) were analyzed by R 3.0 software. Overall HPV, HPV-16/18, and HPV-6/11 infection rates were 32 % (95 % CI 22-44 %), 30 % (95 % CI 24-37 %), and 12 % (95 % CI 9-17 %), respectively. There was a strong association between high-risk HPV-16/18 infection and LC (P < 0.01; OR = 8.07, 95 % CI 5.67-11.48). Our research indicates that there is a higher HPV prevalence in Chinese LC patients compared to LC patients outside of China and that HPV infection significantly increases LC risk.

[Infection rate of human papillomavirus and its association with laryngeal cancer in Chinese: a meta-analysis].

OBJECTIVE: To systematically explore the prevalence of human papillomavirus (HPV) in laryngeal cancer (LC) in Chinese and evaluate the association between HPV infection and laryngeal cancer risk. METHODS: The databases both in English and Chinese were searched. And the studies met the inclusion criteria were included. The prevalence of HPV in LC group and in subgroups, stratified by publishing years and sample storage methods, were analyzed by the R 3.0 software respectively. The cancer risk of HPV infection was estimated by odds ratio (OR) generated by comparisons with the control group. RESULTS: The overall prevalence of HPV was 32% [95% confidence interval (CI): 22%-44%] and the prevalence of high-risk HPV-16/18 and low-risk HPV-6/11 was 30% (95%CI: 24%-37%) and 12% (95%CI: 9%-17%) respectively in Chinese LC patients. The HPV-16/18 infection rate was 24% (95%CI: 15%-35%) in the subgroup between 1992 and 2000 and 32% (95%CI: 24%-41%) in the subgroup from 2001 to 2012 respectively. And no significant difference existed between two subgroups (P = 0.07). The HPV-16/18 infection rate in formalin-fixed paraffin-embedded sample cohort was not significantly different from the fresh-frozen sample cohort [31% (95%CI: 24%-39%) and 28% (95%CI: 18%-42%); P = 0.06]. Meta-analysis showed the overall HPV infection rate in the LC group was significantly higher than in the control group (OR = 15.87 (95%CI: 9.25-27.24); P < 0.01). Moreover, as compared with the control group, the patients in the LC group had a higher infection rate of HPV-16/18 (OR = 8.07 (95%CI: 5.67-11.48); P < 0.01). CONCLUSIONS: HPV infection rates in Chinese LC patients stay at a relatively high level and tend to increase over time. And HPV infection may increase LC risk in Chinese.

Evaluation of sinonasal-related quality of life of 49 patients undergoing endoscopic skull base surgery.

OBJECTIVE: This study aimed to evaluate the sinonasal-related Quality of Life (QoL) in patients undergoing endoscopic skull base surgery. METHODS: A retrospective study was performed, including patients with benign and malignant tumors at a single institution. Each patient completed the 22-Item Sino-Nasal Outcome Test (SNOT-22) and the Empty Nose Syndrome 6 Item Questionnaires (ENS6Q) to assess their perceived QoL at least 2-months after treatment. RESULTS: Forty-nine patients were enrolled in this study. The average score was 25.1 (Stander Deviation [SD] 14.99) for SNOT-22 and 6.51 (SD=5.58) for ENS6Q. Analysis of the overall results for the SNOT-22 showed that olfactory damage was the most serious syndrome. The most frequently reported high-severity sub-domains in SNOT-22 were nasal symptoms and sleep symptoms. Nasal crusting was the most severe item in ENS6Q according to the report. Nine patients (18.4%) had a score higher than 10.5 which indicates the high risk of Empty Nose Syndrome (ENS). SNOT-22 score was related to the history of radiotherapy (p< 0.05), while the ENS6Q score was not. CONCLUSIONS: The possibility of patients suffering from ENS after nasal endoscopic skull base surgery is at a low level, although the nasal cavity structure is damaged to varying degrees. Meanwhile, patients undergoing endoscopic skull base surgery were likely to suffer nasal problems and sleep disorders. Patients who had received radiotherapy have a worse QoL than those without a history of radiotherapy. LEVEL OF EVIDENCE: Level 3.

Electrophysiological Changes on Laryngeal Motor Neuropathways Cause Voice Disorders for Postradiotherapy Patients with Nasopharyngeal Carcinoma.

OBJECTIVE: This study explored electrophysiological changes in the laryngeal motor neuropathway and determined whether lesions in the laryngeal motor cortex (LMC) and its descending tract contribute to voice deterioration and peripheral nerve palsy in patients with nasopharyngeal carcinoma (NPC) postradiotherapy (RT). STUDY DESIGNS: Prospective cohort study. METHODS: Twenty-two patients with NPC at 2 to 4years post-RT (8 female and 14 male), 22 patients with NPC at 8 to 10years post-RT (8 female and 14 male), and 22 healthy individuals (9 female and 13 male) were selected to test their magnetic evoked potentials (MEP), motor nerve conduction, and voice quality using transcranial magnetic stimulation, laryngeal electromyography, and the XION DiVAS acoustic analysis software. Three groups were matched according to approximate age. Multiple comparisons were performed among the three groups. RESULTS: The voice quality of post-RT patients with NPC deteriorated compared to that of healthy individuals. Bilateral LMC and their corticonuclear tracts to the bilateral ambiguous nuclei of post-RT patients with NPC were impaired according to multigroup comparisons of MEP amplitudes, latencies, and resting motor thresholds. The vagus and recurrent laryngeal nerves (RLN) of post-RT patients with NPC were impaired according to multigroup comparisons of the amplitude and latencies of the compound muscle action potential and latencies of f-waves. CONCLUSIONS: The voice quality of patients with NPC deteriorated after RT. The pathogenesis of post-RT voice deterioration may involve radiation-induced injuries to the vagus, RLN, and bilateral LMC. Furthermore, radiation-induced injuries to the bilateral LMC may contribute to vagus and RLN palsies. These findings support the use of transcranial approaches to treating voice disorders and peripheral nerve palsies in post-RT patients with NPC. TRIAL REGISTRATION: ChiCTR2100054425; Electrophysiological Study of Vocal-Fold Mobility Disorders After Radiotherapy for NPC Patients via Magnetic Evoked Potential and Their Correlation with Voice Quality Assessment; https://www.chictr.org.cn/bin/project/edit?pid=144429.

Voice Changes of Patients With Nasopharyngeal Carcinoma in Eleven Years After Radiotherapy: A Cross-Sectional Study.

OBJECTIVES: The objective of this study was to assess voice changes in patients with nasopharyngeal carcinoma (NPC) using subjective and objective assessment tools and to make inferences regarding the underlying pathological causes for different phases of radiotherapy (RT). METHODS: A total of 187 (123 males and 64 females) patients with post-RT NPC with no recurrence of malignancy or other voice diseases and 17 (11 males and 6 females) healthy individuals were included in this study. The patients were equally divided into 11 groups according to the number of years after RT. The acoustic analyses, GRBAS (grade, roughness, breathiness, asthenia, and strain) scales, and Voice Handicap Index (VHI)-10 scores were collected and analyzed. RESULTS: The fundamental frequency (F0) parameters in years 1 and 2 and year 11 were significantly lower in patients with NPC than in healthy individuals. The maximum phonation times in years 1 and 11 were significantly shorter than those in healthy individuals. The jitter parameters were significantly different between year 1 and from years 8 to 11 and the healthy individuals. The shimmer parameters were significantly different between years 1, from years 9 to 11, and healthy individuals. Hoarseness was the most prominent problem compared to other items of the GRBAS. The VHI-10 scores were significantly different between years 1 and 2 and year 11 after RT in patients with NPC. CONCLUSIONS: Voice quality was worse in the first 2 years and from years 8 to 11 but remained relatively normal from years 3 to 7 after RT. Patient-reported voice handicaps began during year 3 after RT. The most prominent problem was perceived hoarseness, which was evident in the first 2 years and from years 9 to 11 after RT. The radiation-induced mucous edema, laryngeal intrinsic muscle fibrosis, nerve injuries, upper respiratory tract changes, and decreased lung capacity might be the pathological reasons for voice changes in post-RT patients with NPC.

Prognostic value of human papillomavirus and squamous cell carcinoma antigen in head and neck squamous cell carcinoma.

To clarify the synergistic influence of human papillomavirus (HPV) status and squamous cell carcinoma antigen (SCCA) mRNA expression on head and neck squamous cell carcinoma (HNSCC) prognosis, HPV DNA presence and SCCA1 and SCCA2 mRNA expression were determined by PCR and quantitative real-time RT-PCR, respectively, in 121 patients with primary HNSCC who were receiving curative treatment. HPV DNA was detected in 28.1% (34/121) of HNSCC cases, and only high-risk types (HPV-16, HPV-33, HPV-35 and HPV-58) were observed. Positive HPV status showed a significantly better prognosis than negative HPV status (P = 0.022). An elevated SCCA2/SCCA1 mRNA ratio was an independent predictor of disease recurrence (P = 0.004). In addition, HPV-negative patients with a high SCCA2/SCCA1 ratio (>0.27) had a significantly lower recurrence-free survival rate than HPV-negative patients with a low SCCA2/SCCA1 ratio (P < 0.011). Our findings revealed that both HPV status and the SCCA2/SCCA1 mRNA ratio are independently associated with prognosis in HNSCC. Patients with both a HPV-negative status and a high SCCA2/SCCA1 ratio might need intensified treatment and rigorous follow up after treatment because of the high risk of recurrence.

Human papillomavirus load and physical status in sinonasal inverted papilloma and squamous cell carcinoma.

BACKGROUND: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP). METHODS: HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group). RESULTS: The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration. CONCLUSIONS: HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.

Prevalence and clinical features of human papillomavirus in head and neck squamous cell carcinoma in Okinawa, southern Japan.

Previous studies from Okinawa, a subtropical island in southern Japan, demonstrated a higher prevalence of human papillomavirus (HPV) in oral carcinoma and a higher incidence of oral and pharyngeal carcinoma than those for mainland Japan. The present study aims to investigate epidemiologic and clinical features of HPV in head and neck squamous cell carcinoma (HNSCC) in Okinawa. A total of 150 DNA samples from 150 Okinawan patients with head and neck squamous cell carcinoma (HNSCC) were screened for HPV sequences by PCR using three consensus primer sets, and HPV types were determined by direct sequencing. The samples were consisted of 46 cases from the hypopharynx, 44 from the oropharynx, 16 from the larynx, 25 from the oral cavity, 10 from the maxillary sinus, and 9 from the nasopharynx. HPV DNA was detected in 45 (30.0%) HNSCCs, and HPV-16 was identified in 86.7% of positive specimens. The highest prevalence of the HPV sequence was found in oropharyngeal carcinomas (50.0%), especially in tonsillar cancer (63.6%). Multivariate analysis showed that oropharyngeal carcinoma (P = 0.002; OR = 5.34; 95% CI = 1.83-15.58), oral cavity carcinoma (P = 0.012; OR = 4.94; 95% CI = 1.43-17.10), and histological poor differentiation (P = 0.011; OR = 4.25; 95% CI = 1.39-13.04) each independently increased the prevalence of HPV infection. The present study reveals that patients with HNSCC, e.g., oropharyngeal and oral cavity carcinomas, in Okinawa have relatively high HPV-16 positive rates and low HPV-18 positive rates comparing with mainland Japan.

HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignant cancer type worldwide. Radiosensitivity has been shown to be significantly increased in patients with human papillomavirus (HPV)-positive HNSCC compared with HPV-negative patients. However, the clinical significance of HPV and its regulatory mechanisms in HNSCC are largely unknown. The aim of our study was to explore the regulatory mechanism of miR-27a-3p in the radiosensitivity of HPV-positive HNSCC cells. METHODS: E6-overexpressing and E6-knockdown HNSCC cell lines were generated and the transfection efficiencies were evaluated by quantitative real-time PCR (RT-qPCR) and western blotting. The expression of miR-27a-3p and DiGeorge syndrome critical region 8 (DGCR8) was examined by RT-qPCR after transfection with E6 overexpressing plasmid or E6 siRNA. The effects of miR-27a-3p on the radiosensitivity of HNSCC cells were explored by a colony formation and TUNEL staining assays. Bioinformatic tools and luciferase reporter assays were used to identify that SMG1 is the direct target of miR-27a-3p. Furthermore, the effect of E6 overexpression on the regulation of the miR-27a-3p/SMG1 axis was investigated. RESULTS: In our study, we found overexpression of HPV E6 upregulated the expression of DGCR8 and miR-27a-3p in HNSCC cells. We next confirmed that DGCR8 positively regulated the expression of miR-27a-3p in HNSCC cells. The luciferase reporter gene results verified that miR-27a-3p targeted the 3'UTR of SMG1 mRNA. MiR-27a-3p mimics transfection resulted in a decrease in SMG1 expression and miR-27a-3p inhibitor transfection increased SMG1 expression. Apoptotic activity of HNSCC cells was significantly increased in miR-27a-3p mimics HNSCC cells compared with control HNSCC cells. After treatment with 4 Gy irradiation, UM-SCC47 cells transfected with miR-27a-3p inhibitor or SMG1 overexpressing plasmid formed more colonies than the corresponding control cells. Furthermore, the rescue experiments demonstrated that HPV16 E6 improved the radiosensitivity of HNSCC cells by targeting miR-27a-3p/SMG1. CONCLUSION: Our study demonstrated that HPV16 E6 activated the DGCR8/miR-27a-3p/SMG1 axis to enhance the radiosensitivity. Our findings might provide a novel therapeutic target to improve the response of HNSCC to radiotherapy.

IAP-1 promoted cisplatin resistance in nasopharyngeal carcinoma via inhibition of caspase-3-mediated apoptosis.

Recurrent/metastatic nasopharyngeal carcinoma (NPC) is known for having a poor prognosis due to its unfavorable response to chemoradiotherapy. However, the specific processes involved remain poorly understood. This study focused on the cisplatin-resistance mechanism in NPC to help understand the occurrence of advanced NPC and aims to explore the potential therapeutic target for cisplatin-resistant NPC. Two cisplatin-resistant NPC cell lines, HNE-1/DDP and CNE-2/DDP, were established and the differentially expressed genes (DEGs) between parental and cisplatin-resistance cell lines, filtering from high-throughput sequencing results, were analyzed. Next, the effects of IAP-1 on cisplatin-resistant nasopharyngeal cancer cell proliferation, apoptosis, drug resistance and associated cell signaling were evaluated in vitro and in vitro. From our bioinformatic results, more than 15,000 differentially expressed genes (DEGs) were found between parental and resistant cell lines. Nine related DEGs were found in the classic platinum resistance pathway, three of which (ATM, IAP-1, and IAP-2) also appeared in the top five differentially expressed pathways, with elevated IAP-1 showing the highest fold change. Further studies revealed that high IAP-1 expression can lead to an increased cisplatin inhibitory concentration and apoptosis inhibition. IAP-1 silencing can induce upregulation of the caspase-3 and enhance the antiproliferation and proapoptotic effects of cisplatin. Clinical data also showed that IAP-1 overexpression was associated with a worse survival status. In summary, in vitro and in vivo experiments demonstrated that IAP-1 plays a vital role in cisplatin resistance by regulating caspase induced apoptosis and serve as a potential novel therapeutic target and a prognostic indicator for advanced NPC.

DGCR8/miR-106 Axis Enhances Radiosensitivity of Head and Neck Squamous Cell Carcinomas by Downregulating RUNX3.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant tumor worldwide, and the radiotherapy effect is strongly associated with human papillomavirus (HPV) infection. Therefore, the aim of our study was to analyze the mechanism of HPV E7 and its effects on radiosensitivity in HNSCC cells. Methods: The mRNA expression of DiGeorge syndrome critical region gene 8 (DGCR8), has-miR-106a, and Runt-related transcription factor 3 (RUNX3) was examined by quantitative real-time PCR (RT-qPCR). The protein expression of DGCR8, E7, RUNX3, caspase-3/cleaved caspase-3, poly(ADP-ribose) polymerase (PARP)/cleaved PARP, and γH2AX was measured by Western blot. The expression level of DGCR8 was measured by immunofluorescence assay. Starbase database (http://starbase.sysu.edu.cn/) was used to analyze the correlation between has-miR-106a-5p and DGCR8. TargetScan database (http://www.targetscan.org/vert_72/) was adopted to calculate the prediction of binding sites. Radiosensitivity was evaluated through clone formation assays and Cell Counting Kit-8 (CCK-8) assays. Results: In our study, we found that the mRNA and protein expression levels of HPV E7 and DGCR8 in HPV-positive HNSCC cells were higher than those in HPV-negative cells. The expression of DGCR8 was increased in FaDu and UM-SCC-4 with E7 overexpression, while the expression of DGCR8 was decreased in UM-SCC-47 and UPCI-SCC-090 with E7 silence. The miR-106a expression was increased after DGCR8 overexpression in FaDu and UM-SCC-4. However, the miR-106a expression was decreased in UM-SCC-47 and UPCI-SCC-090 with E7 silence. In radiation conditions, clone formation assays found that less clones formed in FaDu and UM-SCC-4 cells subsequent to silencing DGCR8 or miR-106a than that in the control group, and more clones were formed in UM-SCC-47 and UPCI-SCC-090 cells overexpressing DGCR8 or miR-106a than that in the control group. Luciferase reporter gene assays verified that miR-106a targeted the 3' untranslated region (UTR) of RUNX3 mRNA. MiR-106a overexpression resulted in a decrease in RUNX3 expression, and miR-106a silence increased RUNX3 expression. Rescue experiments conducted with miR-106a inhibitor restored radiation resistance and reduced DNA damage in radiation condition. Conclusions: Our study indicated that HPV E7 activated DGCR8/miR-106a/RUNX3 axis to enhance radiation sensitivity and provided directions for targeted therapeutic interventions.

DNMT1 Enhances the Radiosensitivity of HPV-Positive Head and Neck Squamous Cell Carcinomas via Downregulating SMG1.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC), which rank the 7th malignant tumors worldwide, is closely related to methylation and HPV infection. Ionizing radiation therapy is the main strategy for HNSCC patients in advanced stage. Previously, HPV-positive HNSCC predict better prognosis than HPV-negative HNSCCs under radiotherapy, however its molecular mechanism is unresolved. SMG1 serves as a potential tumor suppressor in various cancers, including HNSCC. METHODS: The mRNAs and proteins expression of HPV E6/E7, p16, p53, DNMT1, SMG1 were detected after different treatments by qPCR and Western blot. The clone formation ability was measured in radiation dose after different treatments. RESULTS: In our study, the expression of HPV16 E6, DNA Methyltransferase 1(DNMT1) and SMG1 in head and neck carcinomas cell lines was detected by RT-qPCR and Western blot. Forced E6 level in HPV-negative cells by overexpression plasmid promoted the expression of DNMT1, which resulted in decreased SMG1 expression. Silenced SMG1 in HPV-negative HNSCC cells elicited increased radiation sensitivity, suggesting that SMG1 may be an effective switch to regulate the effect of radiotherapy in HNSCC. CONCLUSION: Our study indicated that DNMT1 enhances the radiosensitivity of HPV-positive head and neck squamous cell carcinomas via downregulating SMG1.

Bacteriology of postradiotherapy chronic rhinosinusitis in nasopharyngeal carcinoma patients and chronic rhinosinusitis.

The purpose of this study was to investigate and compare the bacteriology of postradiotherapy chronic rhinosinusitis (postRT-CRS) and chronic rhinosinusitis (CRS) by evaluating the aspiration materials of the maxillary sinus of patients with postRT-CRS and patients with CRS. We collected the secretions of the maxillary sinus from 30 nasopharyngeal carcinoma patients with postRT-CRS and 30 patients with CRS for aerobe/facultative anaerobe bacteria culture. The most common isolates in the postRT-CRS group were Streptococcus viridans, Staphylococcus aureus and Haemophilus influenzae, while those in the CRS group were Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus. Isolated gram-positive coccus rate in postRT-CRS patients was significantly higher than in CRS patients (62.50% compared with 30.00%, respectively; P < 0.05), and isolated gram-negative bacilli rate in postRT-CRS patients was significantly lower than in CRS patients (31.25% compared with 70.00%, respectively; P < 0.05). However, the incidence of positive cultures was not significantly different between the postRT-CRS group and the CRS group (P > 0.05). This study found that there were some differences in bacteriology between postRT-CRS and CRS. Gram-positive coccus was the predominant aerobic/facultative anaerobe pathogenic bacterium in patients with postRT-CRS, and gram-negative bacilli was predominant in CRS patients.

Evaluation of sinonasal-related quality of life of 49 patients undergoing endoscopic skull base surgery

Abstract Objective This study aimed to evaluate the sinonasal-related Quality of Life (QoL) in patients undergoing endoscopic skull base surgery. Methods A retrospective study was performed, including patients with benign and malignant tumors at a single institution. Each patient completed the 22-Item Sino-Nasal Outcome Test (SNOT-22) and the Empty Nose Syndrome 6 Item Questionnaires (ENS6Q) to assess their perceived QoL at least 2-months after treatment. Results Forty-nine patients were enrolled in this study. The average score was 25.1 (Stander Deviation [SD] 14.99) for SNOT-22 and 6.51 (SD = 5.58) for ENS6Q. Analysis of the overall results for the SNOT-22 showed that olfactory damage was the most serious syndrome. The most frequently reported high-severity sub-domains in SNOT-22 were nasal symptoms and sleep symptoms. Nasal crusting was the most severe item in ENS6Q according to the report. Nine patients (18.4%) had a score higher than 10.5 which indicates the high risk of Empty Nose Syndrome (ENS). SNOT-22 score was related to the history of radiotherapy (p < 0.05), while the ENS6Q score was not. Conclusions The possibility of patients suffering from ENS after nasal endoscopic skull base surgery is at a low level, although the nasal cavity structure is damaged to varying degrees. Meanwhile, patients undergoing endoscopic skull base surgery were likely to suffer nasal problems and sleep disorders. Patients who had received radiotherapy have a worse QoL than those without a history of radiotherapy. Level of evidence Level 3.

High-risk type human papillomavirus infection and p16 expression in laryngeal cancer.

BACKGROUND: Oropharyngeal cancers associated with high-risk type human papillomavirus (HR-HPV) infection have better prognosis than virus negative cancers. Similarly, the HPV status in laryngeal cancer (LC) may be associated with better outcome. METHODS: Samples from 88 patients with LC were investigated using the polymerase chain reaction (PCR) and p16 immunohistochemistry for HR-HPV analysis. The cut-off point for p16 overexpression was diffuse (≥75%) tumor expression with at least moderate (+ 2/3) staining intensity. RESULTS: The 5-year cumulative survival (CS) rate was 80.7% in all patients with LC. According to a combination of HR-HPV DNA status and p16 overexpression, subjects with LC were divided into four groups: HR-HPV DNA-positive/p16 overexpression-positive (n = 5, 5.7%; CS = 100%), HR-HPV DNA-positive/p16 overexpression-negative (n = 11, 12.5%; CS =81.8%), HR-HPV DNA-negative/p16 overexpression-positive (n = 0), and HR-HPV DNA-negative/p16 overexpression-negative (n = 72, 81.8%; CS = 79.5%). HR-HPV DNA-positive/p16-positive cases tended to have integrated HPV infection and high viral load, compared with HR-HPV DNA-positive/p16 overexpression-negative cases. CONCLUSIONS: LC patients with HPV infection and high levels of p16 expression might have an improved survival outcome; however, it is necessary to recruit additional LC cases with HPV infection to determine the definitive characteristics of HPV-mediated LC and estimate survival outcome. These results may contribute to the development of a useful method for selecting patients with a potentially fair response to treatment and ensure laryngeal preservation.

Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens.

BACKGROUND: Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries. PATIENTS AND METHODS: This hospital-based case-control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel-Haenszel method. RESULTS: The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC. CONCLUSIONS: ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.