Head Carcinoma Research Articles

243 Sarcomatoid carcinoma in Head and Neck cancers: Clinical features and prognosis

243 Sarcomatoid carcinoma in Head and Neck cancers: Clinical features and prognosis

Exploring the Squamous Cell Carcinoma in Head and Neck: A Literature Review on Pathogenesis, Clinical Symptoms, and Management

Exploring the Squamous Cell Carcinoma in Head and Neck: A Literature Review on Pathogenesis, Clinical Symptoms, and Management

NUT carcinoma in head and neck region: Case report with literature review

Abstract Squamous cell carcinoma (SCC) has several variants based on its histopathological features. Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive variant of SCC, previously described exclusively in midline sites. The histopathological features of NC are similar to poorly differentiated carcinoma or undifferentiated carcinoma. Abrupt keratinization in an otherwise undifferentiated carcinoma is an important diagnostic clue. The confirmatory diagnosis is dependent on molecular techniques such as Immunohistochemistry, Fluorescent in situ hybridization technique or RT-PCR to detect mutations in NUT gene. It is most commonly found in middle aged, in lungs and head and neck regions. Since NC features overlap with poorly differentiated and undifferentiated carcinomas, these cases need to be suspected and evaluated for NUT gene mutations thoroughly. Due to their rarity and less known facts, NC cases are required to be reported on large scale. Here, we report a middle-aged woman with a mass on the forehead diagnosed as NC based on molecular evaluation, with a review of the literature emphasizing the rarity of NUT carcinoma and the importance of careful histopathology as well as immunohistochemistry evaluation.

Myoepithelial Carcinoma of Sinonasal Cavity: Peculiar Diagnosis, Conventional Treatment

Myoepithelial carcinoma is a morphologically diverse tumor which either arises de novo or from the malignant transformation of its benign counterpart i.e. myoepithelioma. These are relatively lesser known entities and are rarely found in head and neck region. Although rare, their first presentation is usually a painless growing mass as seen in our case presentation as well and are infamous for lymph node recurrence and distant metastasis. Due to their clinical presentation and varied morphology these become tedious to diagnose and pose difficulty for a surgeon when presented at a later date due to their effect on the adjacent vital structures. We report a case of myoepithelial carcinoma in head and neck region arising from the nasal cavity, it’s mass effect on the adjacent vital organs and the diagnosis and treatment plan to render the patient free of this tumor, preservation of the vision and keeping the recurrence of the tumor at bay.

PREVALENCE OF OSTEORADIONECROSIS IN HEAD AND NECK IRRADIATED PATIENTS AND ASSOCIATED FACTORS

Objective To assess the association between the prevalence of osteoradionecrosis (ORN) and the time elapsed since the end of head and neck radiotherapy, as well as to assess whether there was difference in the prevalence of ORN related to dental extractions performed before or after radiotherapy. Study Design This cross-sectional observational study evaluated patients who had squamous cell carcinoma in head and neck region, were treated with 3D conformal radiotherapy, and had completed treatment at least 3 months prior to data collection. Data were collected from the patients´ medical records. Results The sample consisted of 90 patients, with a mean age of 62.33 (±9.70) years, who had tumors in mouth/oropharynx (60.00%), larynx (34.44%) or hypopharynx (5.56%), most in advanced stages (69.66%). Patients received a mean radiation dose of 62.99 (±9.74) Gy. The prevalence of ORN was 4.44% and the mean time elapsed since the end of radiotherapy was significantly higher in patients who had ORN (59.75±19.74 months), compared to patients who did not have ORN (34.47±37.91 months) (p=0.036). There was an association between the higher prevalence of ORN and extractions performed after radiotherapy (p=0.005). Conclusion ORN was associated with longer elapsed time after radiotherapy and with extractions performed after radiotherapy. To assess the association between the prevalence of osteoradionecrosis (ORN) and the time elapsed since the end of head and neck radiotherapy, as well as to assess whether there was difference in the prevalence of ORN related to dental extractions performed before or after radiotherapy. This cross-sectional observational study evaluated patients who had squamous cell carcinoma in head and neck region, were treated with 3D conformal radiotherapy, and had completed treatment at least 3 months prior to data collection. Data were collected from the patients´ medical records. The sample consisted of 90 patients, with a mean age of 62.33 (±9.70) years, who had tumors in mouth/oropharynx (60.00%), larynx (34.44%) or hypopharynx (5.56%), most in advanced stages (69.66%). Patients received a mean radiation dose of 62.99 (±9.74) Gy. The prevalence of ORN was 4.44% and the mean time elapsed since the end of radiotherapy was significantly higher in patients who had ORN (59.75±19.74 months), compared to patients who did not have ORN (34.47±37.91 months) (p=0.036). There was an association between the higher prevalence of ORN and extractions performed after radiotherapy (p=0.005). ORN was associated with longer elapsed time after radiotherapy and with extractions performed after radiotherapy.

Salivary protein candidates for biomarkers of oral disorders in people with a crack cocaine use disorder

The use of cocaine and its main derivative, crack, can cause some systemic effects that may lead to the development of some oral disorders. To assess the oral health of people with a crack cocaine use disorder and identify salivary protein candidates for biomarkers of oral disorders. A total of 40 volunteers hospitalized for rehabilitation for crack cocaine addiction were enrolled; nine were randomly selected for proteomic analysis. Intraoral examination, report of DMFT, gingival and plaque index, xerostomia, and non-stimulated saliva collection were performed. A list of proteins identified was generated from the UniProt database and manually revised. The mean age (n=40) was 32 (±8.88; 18-51) years; the mean DMFT index was 16±7.70; the mean plaque and gingival index were 2.07±0.65 and 2.12±0.64, respectively; and 20 (50%) volunteers reported xerostomia. We identified 305 salivary proteins (n=9), of which 23 were classified as candidate for biomarkers associated with 14 oral disorders. The highest number of candidates for biomarkers was associated with carcinoma of head and neck (n=7) and nasopharyngeal carcinoma (n=7), followed by periodontitis (n=6). People with a crack cocaine use disorder had an increased risk of dental caries and gingival inflammation; less than half had oral mucosal alterations, and half experienced xerostomia. As possible biomarkers for 14 oral disorders, 23 salivary proteins were identified. Oral cancer and periodontal disease were the most often associated disorders with biomarkers.

A rare localization of small-cell carcinoma in head and neck area: case report

BackgroundSmall-cell carcinoma (SMCC) of hypopharynx is an extreme rare entity in the head and neck region. It is commonly arising from pulmonary in origin. We report a rare case of small-cell carcinoma of hypopharynx that caused upper airway obstruction in an elderly gentleman.Case presentationA 67-year-old man is presented to otorhinolaryngology clinic with a 4-month history of worsening shortness of breath and stridor. He was heavy tobacco smoker for 60 pack-years. Flexible nasopharyngolaryngoscopy revealed a large mass at the right pyriform fossa extending superiorly and obstructing the laryngeal inlet. He underwent tracheostomy, examination under general anesthesia with tissue biopsy. Histology from tissue biopsy revealed small-cell carcinoma. The positron emission tomography-CT showed exophytic mass from right pyriform sinus with regional and lung pleural metastasis as well. There was the absence of formal staging system for SMCC due to its limited and rare incidence. He was treated with combination of carboplatin and etoposide, similar to the regime for cell carcinoma of lung. The tumor regressed loco-regionally, and his pleural metastasis had shrunk to sub-centimeter in size.ConclusionsTo date, there is very limited data available on head and neck small cell carcinomas to guide treatment recommendations as well as staging system. Paucity of clinical data and outcome about this rare malignancy makes this report a valuable piece of experience to be shared together with existing literature.

Prognosis of adenoid cystic carcinoma in head and neck region treated with different regimens-A single-centre study.

No study has evaluated the impact of regimen on recurrence, metastasis and survival in patients with adenoid cystic carcinoma (ACC). The present study aimed to compare the efficacy of radioactive seed implantation and other regimens in treating ACC, so as to investigate the clinical applicability of radioactive seed implantation and determine the indications for this regimen. A total of 188 patients with ACC in oromaxillofacial region were allocated to four groups according to the treatment regimen: group 1 was treated with a combination of surgery and 125 I seed therapy, group 2 with a combination of surgery and external radiotherapy, group 3 with surgery, whereas group 4 was untreated. The Kaplan-Meier method was used to assess the survival rates, and the Cox regression analyses were used to identify the associated prognostic factors. The overall survival rates of 188 patients and groups 1, 2, 3 and 4 were 85.7%, 75%, 68.2% and 37.5%, respectively. Cox regression analysis revealed that age, T stage, N stage and regimen were independent prognostic factors of survival. Amongst patients with primary ACC, the efficacy of radioactive seed implantation was higher in those with perineural invasion than in those without. Patient age, T stage, N stage and regimen are independent prognostic factors of survival in patients with ACC. Patients treated with surgery combined with postoperative 125 I seed radiotherapy have a higher overall survival rate, and those with perineural invasion are more suitable for radioactive seed implantation therapy.

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort

BackgroundImmune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model.MethodsA single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction.Results201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79.ConclusionsOur updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

Methodology for the development of National Multidisciplinary Management Recommendations using a multi-stage meta-consensus initiative

BackgroundMethods for developing national recommendations vary widely. The successful adoption of new guidance into routine practice is dependent on buy-in from the clinicians delivering day-to-day patient care and must be considerate of existing resource constraints, as well as being aspirational in its scope. This initiative aimed to produce guidelines for the management of head and neck squamous cell carcinoma of unknown primary (HNSCCUP) using a novel methodology to maximise the likelihood of national adoption.MethodsA voluntary steering committee oversaw 3 phases of development: 1) clarification of topic areas, data collection and assimilation, including systematic reviews and a National Audit of Practice; 2) a National Consensus Day, presenting data from the above to generate candidate consensus statements for indicative voting by attendees; and 3) a National Delphi Exercise seeking agreement on the candidate consensus statements, including representatives from all 58 UK Head and Neck Multidisciplinary Teams (MDT). Methodology was published online in advance of the Consensus Day and Delphi exercise.ResultsFour topic areas were identified to frame guideline development. The National Consensus Day was attended by 227 participants (54 in-person and 173 virtual). Results from 7 new systematic reviews were presented, alongside 7 expert stakeholder presentations and interim data from the National Audit and from relevant ongoing Clinical Trials. This resulted in the generation of 35 statements for indicative voting by attendees which, following steering committee ratification, led to 30 statements entering the National Delphi exercise.After 3 rounds (with a further statement added after round 1), 27 statements had reached ‘strong agreement’ (n = 25, 2, 0 for each round, respectively), a single statement achieved ‘agreement’ only (round 3), and ‘no agreement’ could be reached for 3 statements (response rate 98% for each round). Subsequently, 28 statements were adopted into the National MDT Guidelines for HNSCCUP.ConclusionsThe described methodology demonstrated an effective multi-phase strategy for the development of national practice recommendations. It may serve as a cost-effective model for future guideline development for controversial or rare conditions where there is a paucity of available evidence or where there is significant variability in management practices across a healthcare service.

Bioinformatics analysis of the role of aldolase A in tumor prognosis and immunity

Aldolase A (ALDOA) is an enzyme that plays an important role in glycolysis and gluconeogenesis, which is closely related to tumor metabolism. In this study, the overall roles of ALDOA in pan-cancer have been investigated from several aspects using databases and online analysis tools. Using the ONCOMINE database, the expression of ALDOA in various cancers was analyzed. The prognostic role of ALDOA was explored by PrognoScan, GEPIA, and Kaplan–Meier Plotter. The immune-related role of ALDOA and its downstream substrates was decided by TIMER, cBioPortal and String. Our data indicate that ALDOA expression level in lung adenocarcinoma, liver hepatocellular carcinoma, head and neck squamous cell carcinoma is higher than that in normal tissues. Increased expression of ALDOA often indicates a poor prognosis for patients. The correlation between ALDOA and immune infiltration among different tumors is very different. We also investigate the relationship between ALDOA and its upstream/downstream proteins. Our results showed that ALDOA could be used as a biomarker for the tumor prognosis, and could be correlated with the infiltrating levels of macrophages, CD4+ T cells and CD8+ T cells.

A novel CREB5/TOP1MT axis confers cisplatin resistance through inhibiting mitochondrial apoptosis in head and neck squamous cell carcinoma

BackgroundCisplatin resistance is one of the main causes of treatment failure and death in head and neck squamous cell carcinoma (HNSCC). A more comprehensive understanding of the cisplatin resistance mechanism and the development of effective treatment strategies are urgent.MethodsRNA sequencing, RT-PCR, and immunoblotting were used to identify differentially expressed genes associated with cisplatin resistance. Gain- and loss-of-function experiments were performed to detect the effect of CREB5 on cisplatin resistance and mitochondrial apoptosis in HNSCC. Chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay, and immunoblotting experiments were performed to explore the underlying mechanisms of CREB5.ResultsCREB5 was significantly upregulated in cisplatin-resistant HNSCC (CR-HNSCC) patients, which was correlated with poor prognosis. CREB5 overexpression strikingly facilitated the cisplatin resistance of HNSCC cells in vitro and in vivo, while CREB5 knockdown enhanced cisplatin sensitivity in CR-HNSCC cells. Interestingly, the activation of AKT signaling induced by cisplatin promoted nucleus translocation of CREB5 in CR-HNSCC cells. Furthermore, CREB5 transcriptionally activated TOP1MT expression depending on the canonical motif. Moreover, CREB5 silencing could trigger mitochondrial apoptosis and overcome cisplatin resistance in CR-HNSCC cells, which could be reversed by TOP1MT overexpression. Additionally, double-targeting of CREB5 and TOP1MT could combat cisplatin resistance of HNSCC in vivo.ConclusionsOur findings reveal a novel CREB5/TOP1MT axis conferring cisplatin resistance in HNSCC, which provides a new basis to develop effective strategies for overcoming cisplatin resistance.

Survival-related indicators ALOX12B and SPRR1A are associated with DNA damage repair and tumor microenvironment status in HPV 16-negative head and neck squamous cell carcinoma patients

ObjectivesTo investigate prognostic-related gene signature based on DNA damage repair and tumor microenvironment statue in human papillomavirus 16 negative (HPV16-) head and neck squamous cell carcinoma (HNSCC).MethodsFor the RNA-sequence matrix in HPV16- HNSCC in the Cancer Genome Atlas (TCGA) cohort, the DNA damage response (DDR) and tumor microenvironment (TM) status of each patient sample was estimated by using the ssGSEA algorithm. Through bioinformatics analysis in DDR_high/TM_high (n = 311) and DDR_high/TM_low (n = 53) groups, a survival-related gene signature was selected in the TCGA cohort. Two independent external validation cohorts (GSE65858 (n = 210) and GSE41613 (n = 97)) with HPV16- HNSCC patients validated the gene signature. Correlations among the clinical-related hub differentially expressed genes (DEGs) and infiltrated immunocytes were explored with the TIMER2.0 server. Drug screening based on hub DEGs was performed using the CellMiner and GSCALite databases. The loss-of-function studies were used to evaluate the effect of screened survival-related gene on the motility of HPV- HNSCC cells in vitro.ResultsA high DDR level (P = 0.025) and low TM score (P = 0.012) were independent risk factors for HPV16- HNSCC. Downregulated expression of ALOX12B or SPRR1A was associated with poor survival rate and advanced cancer stages. The pathway enrichment analysis showed the DDR_high/TM_low samples were enriched in glycosphingolipid biosynthesis-lacto and neolacto series, glutathione metabolism, platinum drug resistance, and ferroptosis pathways, while the DDR_high/TM_low samples were enriched in Th17 cell differentiation, Neutrophil extracellular trap formation, PD − L1 expression and PD − 1 checkpoint pathway in cancer. Notably, the expression of ALOX12B and SPRR1A were negatively correlated with cancer-associated fibroblasts (CAFs) infiltration and CAFs downstream effectors. Sensitivity to specific chemotherapy regimens can be derived from gene expressions. In addition, ALOX12B and SPRR1A expression was associated with the mRNA expression of insulin like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), mammalian target of rapamycin (MTOR), and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) in HPV negative HNSCC. Down-regulation of ALOX12B promoted HPV- HNSCC cells migration and invasion in vitro.ConclusionsALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs. The specific drug pattern was determined by the gene signature.

Comprehensive Analysis of LINC01615 in Head and Neck Squamous Cell Carcinoma: A Hub Biomarker Identified by Machine Learning and Experimental Validation.

Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients. Methods We downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and p value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration. Results Cox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells. Conclusion LINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.

A Cell Component-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma Based on the Tumor Microenvironment.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with a high mortality rate. The tumor microenvironment (TME) is composed of numerous noncancerous cells that contribute to tumorigenesis and prediction of therapeutic effects. In this study, we aimed to develop a cell component-related prognostic model based on TME. We screened cell component enrichments from samples in The Cancer Genome Atlas (TCGA) HNSCC cohort using the xCell algorithm. Univariate Cox and multivariate Cox regression analyses were performed to establish an optimal independent risk model. The prognostic value of the model was further validated using Gene Expression Omnibus datasets. We found that patients in the low-risk group had a better outcome and activated immunity and may benefit more from the immune checkpoint inhibitor therapy. We also explored microRNAs (miRNAs) that may regulate these identified cell components, and 11 miRNA expression levels influenced the overall survival time. Moreover, their target mRNAs were differentially expressed in TCGA cohort and enriched in pathways of cell cycle pathways, extracellular matrix receptor interaction, human papillomavirus infection, and cancer. In summary, our cell component-related signature was a promising prognostic biomarker that provides new insights into the predictive value of nontumor components in the TME.

Treatment-Interval Changes in Serum Levels of Albumin and Histidine Correlated with Treatment Interruption in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma Completing Chemoradiotherapy under Recommended Calorie and Protein Provision.

Simple SummaryTreatment interruption during concurrent chemoradiotherapy (CCRT) jeopardizes the outcomes of patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC), which is associated with increased toxicity during CCRT. Nonetheless, we found that under the provision of recommended calories (25 kcal/kg/day) and protein (1 g/kg/day) throughout the treatment course, treatment-interval changes in serum albumin and histidine levels—not treatment toxicity—greatly contributed to the interruption of treatment in patients with LAHNSCC. We believe that serum levels of albumin and histidine should be integrated into the routine nutritional assessment of patients undergoing CCRT.We investigated risk factors for treatment interruption (TI) in patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC) following concurrent chemoradiotherapy (CCRT), under the provision of recommended calorie and protein intake; we also evaluated the associations between clinicopathological variables, calorie and protein supply, nutrition–inflammation biomarkers (NIBs), total body composition change (TBC), and a four-serum-amino-acid metabolite panel (histidine, leucine, ornithine, and phenylalanine) among these patients. Patients with LAHNSCC who completed the entire planned CCRT course and received at least 25 kcal/kg/day and 1 g of protein/kg/day during CCRT were prospectively recruited. Clinicopathological variables, anthropometric data, blood NIBs, CCRT-related factors, TBC data, and metabolite panels before and after treatment were collected; 44 patients with LAHNSCC were enrolled. Nine patients (20.4%) experienced TIs. Patients with TIs experienced greater reductions in hemoglobin, serum levels of albumin, uric acid, histidine, and appendicular skeletal mass, and suffered from more grade 3/4 toxicities than those with no TI. Neither increased daily calorie supply (≥30 kcal/kg/day) nor feeding tube placement was correlated with TI. Multivariate analysis showed that treatment-interval changes in serum albumin and histidine levels, but not treatment toxicity, were independently associated with TI. Thus, changes in serum levels of albumin and histidine over the treatment course could cause TI in patients with LAHNSCC following CCRT.

Plac1 Remodels the Tumor Immune Evasion Microenvironment and Predicts Therapeutic Response in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC or HNSC) is the sixth most common cancer worldwide. Placenta-specific 1 (Plac1) belongs to the cancer testis antigen family and is highly expressed in malignant cells in HNSC. However, the biological function and prognostic value of plac1 in HNSC are still unclear. In the current research, we performed a comprehensive analysis of plac1 using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) bulk RNA sequencing databases as well as a single-cell sequencing dataset. We constructed a 15-gene prognostic signature through screening plac1-related immunomodulators and validated its efficiency and accuracy in immunotherapy cohorts and a pancancer database. We found that plac1 expression level is a prognostic predictor of poor overall survival in patients with HNSC. Plac1 is associated with epithelial–mesenchymal transition and tumor invasion. Plac1 has a “dual immunosuppressive function” on tumor microenvironment. On one hand, plac1-positive cells promote extracellular matrix formation and suppress immune cell infiltration. On the other hand, plac1-positive cells enhance the interaction between dendritic cells and macrophages, which further suppresses antitumor immunity. Finally, we constructed a 15-gene prognostic signature, the efficiency and accuracy of which were validated in immunotherapy cohorts and a pancancer database. In conclusion, plac1 is a promising candidate biomarker for prognosis, a potential target for immunotherapy, and a novel point for studying the immunosuppressive mechanisms of the tumor microenvironment in HNSC.

Postoperative radiotherapy may not be necessary for locally advanced head and neck squamous cell carcinoma: a case-match multicentre study

BackgroundSome head and neck cancer surgeons found that many patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) without postoperative radiotherapy (PORT) also have a good prognosis. The purpose of this study was to determine the effect of PORT on survival in patients with LA-HNSCC.MethodsA case-match cohort analysis was performed at two institutions on patients with LA-HNSCC. Patients who received surgery alone were case-matched 1: 1 with patients treated by surgery plus PORT based on pT, pN, tumor subsite etc.Results114 patients were matched into 57 pairs, with a median follow-up period of 40.2 months. No difference in overall survival (OS, HR 0.88; 95% CI 0.50–1.58; P = 0.79) or disease-specific survival (DFS, 0.86; 95% CI 0.50–1.50; P = 0.76) was observed with no PORT.ConclusionsPORT isn’t necessary for patients with LA-HNSCC who are treated for the first time as long as the head and neck cancer surgeon adhere to appropriate surgical concepts. The indications of PORT for patients with LA-HNSCC need to be further discussed.

Prediction of Necroptosis-Related Markers in Head and Neck Carcinoma by Bioinformatics.

Necroptosis is a form of programmed cell death that has recently been shown to be important in the progression of head and neck cancer (HNC). Noncoding RNAs (ncRNAs) are known to function in cell death and tumor formation. In this study, we focused on microRNAs (miRNA) that play roles in necroptosis and the progression of HNC. We collected miRNA expression data, related clinical data of patients with HNC, and miRNA data related to necroptosis. A prognostic multimiRNA molecular marker was generated based on differential expression analysis and univariate and multivariate Cox regression analyses. Target genes of the prognosis-related miRNAs were identified, and their functions were evaluated by Gene Ontology Enrichment Analysis to reveal the processes the miRNAs may be involved in. Eight potentially prognostic miRNAs were identified through differential expression analysis: miR-331-3p, miR-181d-5p, miR-181b-5p, miR-500a-3p, miR-425-5p, miR-181a-5p, miR-141-3p, and miR-200a-5p. Multivariate Cox regression identified the risk score as an independent prognostic factor (univariate Cox regression results: hazard ratio (HR): 2.2028, 95% confidence interval (CI): 1.2640–3.8388, P = 0.0053; multivariate Cox regression results: HR: 2.4168, 95% CI: 1.3743–4.2501, P = 0.0022). Survival curve analysis revealed that patients with a high risk score had a bad prognosis (P = 0.0109). A receiver operating characteristic curve showed that the model has a certain prediction ability. We identified 187 miRNA-related genes, which were enriched in “cell cycle” and “cellular senescence.” In conclusion, this study identified eight novel miRNA markers for predicting the prognosis of patients with HNC and paved the way for future research on necroptosis-related genes.

Dual function of SF3B2 on chromatin and RNA to regulate transcription in head and neck squamous cell carcinoma

RNA is spliced concomitantly with transcription and the process is organized by RNA splicing factors, transcriptional regulators, and chromatin regulators. RNA is spliced in close proximity to transcription machinery. Hence, some RNA splicing factors may play a role in transcription. Here, we show that the splicing factor SF3B2 binds to gene regulatory elements and mRNA to modulate transcription and RNA stability in head and neck squamous cell carcinoma cells. High SF3B2 expression leads to poor prognosis in patients with head and neck squamous cell carcinoma and to progression of tumor growth in mice. SF3B2 promotes tumor growth, owing to its involvement in activation of gene expression associated with mitochondrial electron transport and transcription regulatory region DNA binding. SF3B2 is enriched around the promoter element on chromatin and the transcription termination site on RNA. SF3B2 is involved in the regulation of RNA stability. According to the SF3B2-binding profile, SF3B2 regulates RNA polymerase II activity, in addition to regulating RNA splicing. Mechanistically, SF3B2 promotes the binding of structural maintenance of chromosomes 1A and CCCTC-binding factor (CTCF) to the SF3B2-binding genomic regions. SF3B2 also modulates CTCF transcriptional activity. Our findings indicate that SF3B2 has a dual function in both transcription and RNA stability, leading to head and neck squamous cell carcinoma progression.