C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2.

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48's function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

Upregulated YTHDF1 associates with tumor immune microenvironment in head and neck squamous cell carcinomas.

Background: The nature of the tumor immune microenvironment (TME) is essential for the head and neck squamous cell carcinomas (HNSCC) initiation, prognosis, and response to immunotherapy. However, its gene regulatory network remains to be elucidated. Methods: To identify N6-methyladenosine (m6A) regulators that are involved in regulating the HNSCC TME, a computational screen was applied to The Cancer Genome Atlas (TCGA) HNSCC patient samples. The effects of mutation, copy number variation (CNV), and transcriptional regulation on YTHDF1 expression were analyzed. We analyzed the TME infiltration, cancer-immunity cycle activities, and YTHDF1-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: Among the 24 m6A regulators, 3 factors (YTHDF1, ELAVL1, and METTL3) were highly correlated with TME infiltration. As the top candidate, YTHDF1 was up-regulated and amplified in HNSCC. YTHDF1 promoter gains active histone marks and high chromatin accessibility, which might be transcriptionally activated by SOX2 and TP63. Moreover, YTHDF1 expression significantly associates with tumor malignant phenotype in HNSCC, which has a positive correlation with CD4+ T cells and a negative correlation with CD8+ T cells infiltration. Specifically, YTHDF1 expression is negatively associated with the cancer-immunity cycle and immune checkpoint inhibitors. In terms of the underlying biological mechanisms, YTHDF1 may interact with YTHDF2/3 to regulate several vital immune-related pathways. Conclusions: We identify YTHDF1 associated with TME and elucidate an underlying mechanism of immune escape in HNSCC, which might be used as a predictive marker in guiding immunotherapy.

A 25-gene panel predicting the benefits of immunotherapy in head and neck squamous cell carcinoma.

Tumor mutation burden high (TMB-H) is widely used in the guidance of immune checkpoint blocking (ICB) therapy for head and neck squamous cell carcinoma (HNSCC) patients. However, a few patients still had a poor response. Therefore, it is necessary to investigate a better model to guide ICB therapy. We constructed a genomic mutation model conducive to ICB therapy using an available HNSCC dataset. Moreover, treatment procedures for patients with HNSCC from our internal cohort confirmed this model. Here, a genomic mutation signature based on a list of 25 candidate genes that are favorable for immunotherapy was established. Patients with combined mutation had a respectable clinical outcome under ICB treatment. Notably, compared with patients who obtained TMB-H (TMB ≥ 10, but did not have combined mutation), those patients with TMB-L (TMB < 10) and combined mutation acquired remarkably beneficial overall survival. Moreover, the combined mutation signature predicting the survival status of patients was superior to TMB, with a Youden index of 0.55. Furthermore, higher immune cell infiltration levels, more active cancer-immunity cycle activities and immune response pathways were observed in patients with combined mutation. Finally, our internal cohort further confirmed that combined mutated patients can benefit from ICB therapy rather than any other patients.

Characteristics of 43 multiple auricular deformity case families and auricle morphology in 463 microtia patients in South China.

BACKGROUND: Earlier studies have suggested that microtia is a genetic disease with a worldwide incidence of microtia is between 0.83/10,000 and 17.40/10,000. For microtia, auricle morphology is the most crucial characteristic. However, no studies have been performed to characterize the genetic similarity of microtia and auricle morphology similarity. For the sporadic patients, the relationship between the gestational age of parents and the incidence of microtia is unclear. To obtain the characteristics of auricular deformity multiple case family (AD-MCF) and clarify the relationship between genetic similarity and auricle morphology similarity in AD-MCF. METHODS: This study included 463 AD patients who were diagnosed by Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from 2013 to 2019. Among these patients, 116 are from 43 MCF and the other 347 patients are sporadic. For the patients from families, the disease status of the four generations of immediate family members and the family tree map were collected to analyze the similarity of auricle shape in family members. A score evaluated the similarity of auricle shape according to the structure of the residual ear and the similarity in the morphology of each auricle. Moreover, the population distribution of AD and the gestational age of patients were further analyzed. RESULTS: From 2013 to 2019, a total of 463 patients were diagnosed as microtia in our hospital. There were 427 patients with unilateral disease and 36 patients with bilateral disease. Among them, 116 patients were from 34 families and 9 de novo families. The total scores of patients in different genetic difference levels were compared and were found significantly different (P<0.001). Moreover, 58.14% of families were consistent with the law of chromosomal recessive genetic diseases. Importantly, we found that the gestational age of father in microtia de novo families is 30.94±0.75, and mother in de novo is 28.39±0.73 that is significantly higher than the gestational ages of parents from microtia families with P value =0.0001. CONCLUSIONS: The auricle similarity between family members is positively related to the genetic distance between family members. The microtia patients are potentially associated with the gestational ages of parents.

Local Versus General Anesthesia for Balloon Dilation of the Eustachian Tube: A Single-Center Retrospective Study in a Chinese Population.

OBJECTIVE: To compare local anesthesia (LA) versus general anesthesia (GA) for balloon dilation of the Eustachian tube (BDET) using the Bielefeld Dilation System in a Chinese population with obstructive Eustachian tube dysfunction (OETD). METHODS: A total of 49 patients with OETD undergoing BDET under either LA or GA were included in the present study. Intraoperative blood pressure, heart rate, and pain sensation were recorded. The surgical outcome was assessed by Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) symptom scores and positive Valsalva maneuver at baseline, 1 day, 2-, 4-, 12-, 24-, and 52-week follow-up. RESULTS: Balloon dilation of the Eustachian tube procedures were successfully completed in all patients without adverse effects. The visual analog scale score for maximal pain during the surgical procedure in the LA group was 6.1 ± 1.0. Intraoperative blood pressure and heart rate were higher in the LA group compared with the GA group. The duration and costs of surgery were significantly reduced in the LA group compared with the GA group. Normalization of ETDQ-7 scores at 12-week and 52-week follow-up was observed in 71.9% (23/32) and 63.3% (19/30) of patients in the LA group, respectively, which was comparable to that of the GA group. Although improvement in positive Valsalva maneuver was observed in both groups after BDET, more patients reported positive Valsalva maneuver in the GA group compared with the LA group at 12-week and 52-week follow-up. In total, 96.0% (24/25) of patients in the LA group and 95.8% (23/24) of patients in the GA group would choose LA if BDET was needed again. CONCLUSION: Balloon dilation of the Eustachian tube under LA is safe and feasible in a Chinese population. The surgical outcome of BDET is comparable between under LA and GA during 52-week follow-up. Further studies are needed to address management of intraoperative pain and determine longer follow-up outcome for BDET under LA.

Modified Postauricular Incision for Preservation of the Lesser Occipital Nerve and the Great Auricular Nerve in Ear Surgery.

OBJECTIVE: To describe the feasibility of preserving the lesser occipital nerve (LON) and the great auricular nerve (GAN) in postauricular incision in ear surgery. METHODS: The distribution of the LON and the GAN was first identified in human cadavers. Then a clinical study was performed in 34 patients who underwent middle ear surgery between September 2016 and January 2017. Patients were divided into the conventional incision group and the modified incision group, according to incision types, and underwent sensory testing and subjective evaluation of auricular numbness after surgery at different times. RESULTS: Most frequently, the auricular branches of the LON went into the postauricular groove at the same height of inferior crus of antihelix. The vertical dimension from the intersection of the highest auricular branch of the GAN and postauricular groove to intertragic notch ranged from 5.7 to -4.2 mm. Preservation of the LON and the GAN reduced sensory loss in the modified incision group compared to the conventional incision group. CONCLUSION: Preservation of the LON and the GAN with modified postauricular incision can reduce postoperative auricular numbness.

Buteyko breathing technique for obstructive Eustachian tube dysfunction: Preliminary results from a randomized controlled trial.

PURPOSE: To assess the effectiveness of Buteyko breathing technique in patients with obstructive Eustachian tube dysfunction (ETD). MATERIALS AND METHODS: Fifty-one patients (77 ears) aged between 21 and 62 years were randomized to Buteyko breathing in conjunction with medical management (nasal steroid) group or medical management alone group. The Eustachian Tube Dysfunction Questionnaire (ETDQ-7) symptom scores, tympanogram, positive Valsalva maneuver were evaluated at baseline, 6-week and 12-week follow-up. RESULTS: Normalization of ETDQ-7 symptom scores at 6-week follow-up was observed in 30.0% (12/40) of the Buteyko breathing group versus 16.2% (6/37) of the controls (P > 0.05). At 12-week follow-up, the ratio rose to 50.0% (20/40) in the Buteyko breathing group and 24.3% (9/37) in the controls (P < 0.05). Tympanogram normalization at 12-week follow-up was observed in 53.6% (15/28) of the Buteyko breathing group versus 26.9% (7/26) of the controls (P < 0.05). The Buteyko breathing group showed slight improvement in positive Valsalva maneuver at 6- and 12-week follow-up (P > 0.05). CONCLUSIONS: Our study shows that Buteyko breathing technique might be an effective adjunctive intervention in treatment of obstructive ETD, especially for those patients who are refractory to medical treatment and cannot afford Eustachian tube balloon dilation surgery.