A human-specific cytotoxic neopeptide generated by the deafness gene Cingulin.

Accumulation of mutant proteins in cells can induce proteinopathies and cause functional damage to organs. Recently, the Cingulin (CGN) protein has been shown to maintain the morphology of cuticular plates of inner ear hair cells and a frameshift mutation in CGN causes autosomal dominant non-syndromic hearing loss. Here, we find that the mutant CGN proteins form insoluble aggregates which accumulate intracellularly and lead to cell death. Expression of the mutant CGN in the inner ear results in severe hair cell death and hearing loss in mice, resembling the auditory phenotype in human patients. Interestingly, a human-specific residue (V1112) in the neopeptide generated by the frameshift mutation is critical for the aggregation and cytotoxicity of the mutant human CGN. Moreover, the expression of heat shock factor 1 (HSF1) decreases the accumulation of insoluble mutant CGN aggregates and rescues cell death. In summary, these findings identify mutant-specific toxic polypeptides as a disease-causing mechanism of the deafness mutation in CGN, which can be targeted by the expression of the cell chaperone response regulator HSF1.

Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea.

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.

AAV-mediated Gpm6b expression supports hair cell reprogramming.

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

Primary Surgical Management of Laryngeal Neuroendocrine Neoplasms: A Single Institution Case Series.

Objective: Laryngeal neuroendocrine neoplasms (NENs) are rare diseases. A single institution retrospective study was done of the outcome of patients with laryngeal NENs who undergo primary surgery as the first treatment modality. Methods: Retrospective analysis of medical records of patients with laryngeal NENs between 2009 and 2018. Cases were classified by applying the 2022 World Health organization Classification of Head and Neck Tumors (5th edition). Results: Six patients were eligible at our tertiary center: 1 large cell neuroendocrine carcinoma (NEC), 3 small cell NEC, 1 neuroendocrine tumor grade 1, and 1 neuroendocrine tumor grade 2. All admitted patients received upfront surgeries, including 3 transoral CO2 laser surgeries and 3 total laryngectomies with or without elective neck dissection. Four patients underwent subsequent chemoradiotherapy. Although 3 patients had recurrent disease and distal metastasis, the overall survival was generally improved. Conclusion: According to our institutional experience, upfront surgery in the first-line setting of a multi-modality approach with adjuvant chemoradiotherapy plays a very important role in managing laryngeal NECs, and may confer additional survival benefit in some patients of the large cell carcinoma subgroup.

[Diagnosis and treatment of congenital temporal bone cholesteatoma].

Congenital temporal bone cholesteatoma is a rare lesion in otolaryngology.The disease is locally invasive and may lead to significant complications,including hearing loss（conductive or sensorineural）, temporal bone destruction and intracranial invasion. This article reviews the characteristic symptoms of congenital temporal bone cholesteatoma, testing and imaging of the disease, stage and the current treatment options in order to promote awareness to this rare disease entity and perform early surgical treatment, effectively avoid the destruction of the temporal bone and its surrounding structures, thereby reducing the occurrence of complications. By improving the understanding of the disease and performing early surgical treatment, the destruction of the temporal bone and its surrounding structures can be effectively avoided, thereby reducing the occurrence of complications.

Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage.

Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1 expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.Abbreviations: AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.

[Clinical characteristics of 1330 elderly patients with voice diseases diagnosed by electronic laryngoscope].

Objective:To investigate the clinical features of electronic laryngoscope in the diagnosis of senile voice diseases. Methods:Elderly patients who visited the outpatient department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital from September 2014 to September 2018 were collected. All patients came in with hoarseness. All patients were routinely diagnosed by electronic laryngoscopy and the results were analyzed. Results:A total of 1330 elderly patients aged 60 years and over were enrolled in this study, including 924 males and 406 females. There are significant differences in the distribution of various voice diseases in different genders（P<0.05）. Among male elderly patients, the top three were: 239 cases of throat malignant tumor（25.87%）, 182 cases of vocal cord benign proliferative disease（19.70%）, 147 cases of vocal cord leukoplakia（15.91%）. Among female elderly patients, the top three diseases were: 183 cases（45.07%） of vocal cord benign proliferative disease, 70 cases（17.24%） of laryngitis, 66 cases（16.26%） of vocal cord paralysis. There were significant differences in the distribution of different voice disorders among the three different age groups of elderly patients. The top three elderly patients aged 60-69 years were: 298 cases（35.06%） of vocal cord benign proliferative diseases, 132 cases（15.53%） of laryngopharyngeal malignant tumors, 104 cases（12.24%） of vocal cord paralysis. The top three elderly patients aged 70-79 years were: 91 cases（24.20%） of laryngopharyngeal malignant tumors, 57 cases（15.16%） of vocal cord benign proliferative diseases, 55 cases（14.63%） of vocal cord paralysis. The top three elderly patients aged 80 years and above were: 25 cases（24.04%） of laryngopharyngeal malignant tumors, 21 cases（20.19%） of vocal cord paralysis, 16 cases（15.38%） of the vocal cords are not closed completely. There were also significant differences in the distribution of various voice diseases among smokers（P<0.05）. Conclusion:With the acceleration of the aging of society, we should pay more attention to the voice of the elderly. The most common disease in elderly women with hoarseness is benign hyperplastic vocal cord disease. The high incidence of laryngeal malignant tumors in elderly male hoarseness patients who smoke should be paid special attention to. Electronic laryngoscope plays an important role in the diagnosis of voice diseases in elderly patients.

[The clinical features of Castleman disease in the head and neck].

Objective:To investigate the clinicopathological features, treatment and prognosis of Castleman disease in the head and neck. Methods:The clinical and pathological data of 18 patients with Castleman disease of the head and neck in Nanjing Drum Tower Hospital from 2007 to 2021 were retrospectively analyzed. There were 14 cases of unicentric type and 4 cases of multicentric type. The clinical characteristics, treatment and prognosis were analyzed. Results:Among the 18 cases of Castleman disease in the head and neck, 1 case was located in the parotid gland, 1 case was behind the ear, 1 case was in the parapharyngeal space, 3 cases were in the neck region Ⅰ, 2 cases were supraclavicular, 2 cases were in the neck region Ⅲ, the rest were located in more than two subregions of the neck. In patients with unicentric type, no tumor recurrence and progression were found in the postoperative re-examination with neck Doppler ultrasound and CT; in the multicentric type, multiple organ dysfunction, such as edema of both lower extremities, hepatosplenomegaly, and cough, were found. Of the 4 patients with multicentric type, only 1 patient received chemotherapy, and the remaining 3 patients refused chemotherapy and only received symptomatic treatment. All patients survived during follow-up, but the disease of multicentric patients progressed significantly, and the number of involved lymph nodes increased, and hepatosplenomegaly were found in some patients. Conclusion:Castleman disease of the head and neck is mostly unicentric type, which is manifested as multiple asymptomatic enlarged lymph nodes in the neck. The surgical resection is effective and the prognosis is good. Multicentric Castleman disease of the head and neck has complex clinical symptoms and involves multiple organs over time, requiring follow-up treatment.

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.

Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes.

Dync1li1, a subunit of cytoplasmic dynein 1, is reported to play important roles in intracellular retrograde transport in many tissues. However, the roles of Dync1li1 in the mammalian cochlea remain uninvestigated. Here we first studied the expression pattern of Dync1li1 in the mouse cochlea and found that Dync1li1 is highly expressed in hair cells (HCs) in both neonatal and adult mice cochlea. Next, we used Dync1li1 knockout (KO) mice to investigate its effects on hearing and found that deletion of Dync1li1 leads to early onset of progressive HC loss via apoptosis and to subsequent hearing loss. Further studies revealed that loss of Dync1li1 destabilizes dynein and alters the normal function of dynein. In addition, Dync1li1 KO results in a thinner Golgi apparatus and the accumulation of LC3+ autophagic vacuoles, which triggers HC apoptosis. We also knocked down Dync1li1 in the OC1 cells and found that the number of autophagosomes were significantly increased while the number of autolysosomes were decreased, which suggested that Dync1li1 knockdown leads to impaired transportation of autophagosomes to lysosomes and therefore the accumulation of autophagosomes results in HC apoptosis. Our findings demonstrate that Dync1li1 plays important roles in HC survival through the regulation of autophagosome transportation.

METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). METHODS: The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. RESULTS: M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. CONCLUSIONS: METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.

Superparamagnetic Iron Oxide Nanoparticles: Cytotoxicity, Metabolism, and Cellular Behavior in Biomedicine Applications.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated and applied in the field of biomedicine due to their excellent superparamagnetic properties and reliable traceability. However, with the optimization of core composition, shell types and transfection agents, the cytotoxicity and metabolism of different SPIONs have great differences, and the labeled cells also show different cellular behaviors. Therefore, a holistic review of the construction and application of SPIONs is desired. This review focuses the advances of SPIONs in the field of biomedicine in recent years. After summarizing the toxicity of different SPIONs, the uptake, distribution and metabolism of SPIONs in vitro were discussed. Then, the regulation of labeled-cells behavior is outlined. Furthermore, the major challenges in the optimization process of SPIONs and insights on its future developments are proposed.

Cochlear implant-based electric-acoustic stimulation modulates neural stem cell-derived neural regeneration.

Cochlear implantation is considered to be the best therapeutic method for profound sensorineural hearing loss, but insufficient numbers of functional spiral ganglion neurons hinder the clinical effects of cochlear implantation. Stem cell transplantation has the potential to provide novel strategies for spiral ganglion neuron regeneration after injury. However, some obstacles still need to be overcome, such as low survival and uncontrolled differentiation. Several novel technologies show promise for modulating neural stem cell behaviors to address these issues. Here, a device capable of electrical stimulation was designed by combining a cochlear implant with a graphene substrate. Neural stem cells (NSCs) were cultured on the graphene substrate and subjected to electrical stimulation transduced from sound waves detected by the cochlear implant. Cell behaviors were studied, and this device showed good biocompatibility for NSCs. More importantly, electric-acoustic stimulation with higher frequencies and amplitudes induced NSC death and apoptosis, and electric-acoustic stimulation could promote NSCs to proliferate and differentiate into neurons only when low-frequency stimulation was supplied. The present study provides experimental evidence for understanding the regulatory role of electric-acoustic stimulation on NSCs and highlights the potentials of the above-mentioned device in stem cell therapy for hearing loss treatment.

Delayed postoperative complications in 624 consecutive cochlear implantation cases.

Background: Sensorineural hearing loss can be cured by cochlear implantation (CI), but complications can occur. Based on when the complications develop, they are categorized as intraoperative complications, early postoperative complications, or delayed postoperative complications (>3 months after the surgery).Aims/objectives: We aimed to investigate the occurrence of delayed complications after CI surgery, and identify appropriate management methods.Material and methods: We analyzed 624 sensorineural hearing loss patients who had been consecutively treated with CI using the conventional surgical technique in our institution and had been followed-up until September 2017.Results: A total of 43 (6.86%) patients out of the 624 CIs (627 ears) reported complications, and 9 (1.44%) were major complications and 34 (5.42%) were minor complications. Wound infection and device failure were the most common major complications, and hematoma was the most common minor complication.Conclusions and significance: CI surgery is a relatively mature technology; the incidence of complications is low, and with early diagnosis and treatment most complications have a good prognosis. Head trauma was the main reason for children's complications, and patients and guardians should be given good education preoperatively about how to manage the CI postoperatively.

Potential prognostic markers and significant lncRNA-mRNA co-expression pairs in laryngeal squamous cell carcinoma.

lncRNA-mRNA co-expression pairs and prognostic markers related to the development of laryngeal squamous cell carcinoma (LSCC) were investigated. The lncRNA and mRNA expression data of LSCC in GSE84957 and RNA-seq data of 112 LSCC samples from TCGA database were used. Differentially expressed genes (DEGs) and lncRNAs (DE-lncRNAs) between LSCC and para-cancer tissues were identified. Co-expression analysis of DEGs and DE-lncRNA was conducted. Protein-protein interaction network for co-expressed DEGs of top 25 DE-lncRNA was constructed, followed by survival analysis for key nodes in co-expression network. Finally, expressions of several DE-lncRNAs and DEGs were verified using qRT-PCR. The lncRNA-mRNA network showed that ANKRD20A5P, C21orf15, CYP4F35P, LOC_I2_011146, XLOC_006053, XLOC_I2_003881, and LOC100506027 were highlighted in network. Some DEGs, including FUT7, PADI1, PPL, ARHGAP40, MUC21, and CEACAM1, were co-expressed with above lncRNAs. Survival analysis showed that PLOD1, GLT25D1, and KIF22 were significantly associated with prognosis. qRT-PCR results showed that the expressions of MUC21, CEACAM1, FUT7, PADI1, PPL, ARHGAP40, ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, LOC_I2_011146, and XLOC_006053 were downregulated, whereas the expression of LOC100506027 was upregulated in LSCC tissues. PLOD1, GLT25D1, and KIF22 may be potential prognostic markers in the development of LSCC. C21orf15-MUC21/CEACAM1/FUT7/PADI1/PPL/ARHGAP40 are potential lncRNA-mRNA pairs that play significant roles in the development of LSCC.

Presurgical platelet-lymphocyte ratio for prognosis in advanced hypopharyngeal squamous cell carcinoma in individuals undergoing radical resection.

BACKGROUND: Patient prognosis in hypopharyngeal carcinoma remains difficult to predict, necessitating new, readily available biomarkers. OBJECTIVE: Platelet-lymphocyte ratio (PLR)'s effects on recurrence-free survival (RFS) and overall survival (OS) were evaluated in individuals undergoing radical resection for advanced hypopharyngeal squamous cell carcinoma (HSCC). METHODS: A total of 89 patients were retrospectively assessed. PLR, and derived neutrophil-lymphocyte (dNLR) and neutrophil-lymphocyte (NLR) ratios were determined based on complete blood count. Then, the prognostic values of PLR, dNLR and NLR were assessed by univariate and multivariate Cox regression analyses adjusted for disease-specific prognostic factors. Endpoints of interest were RFS and OS. RESULTS: The optimal cutoff of PLR was 98.815, based on which individuals were categorized into the high- (PLR ≥98.815) and low- (PLR <98.815) PLR groups. High PLR (p = .022) had a significant association with reduced RFS, which still showed significance in multivariable analysis (HR = 2.020, 95%CI: 1.076-3.794, p = .029). In univariate analysis, PLR (p = .046) and positive surgical margin (p = .021) also had significant associations with OS. CONCLUSION: Elevated PLR has associations with increased risk of recurrence and reduced survival in advanced HSCC cases undergoing radical resection. High presurgical PLR may independently predict RFS. Therefore, further multi-institutional prospective studies are needed to better characterize the role of pre-operative blood PLR as prognostic factors in HSCC.

[Research progress in the treatment of sensorineural olfactory dysfunction].

Sensorineural olfactory dysfunction refers to the reduction or distortion of sensory intensity due to insufficient reception or processing of stimulation by olfactory receptors, olfactory sensory neurons or central nervous system. As olfactory dysfunction can affect patients' physical and mental health and even safety of life and the etiology of sensorineural olfactory dysfunction is complicated, it has great clinical significance for understanding the development of olfactory dysfunction's treatment. This article summarizes the current promising treatment for sensorineural olfactory dysfunction, including drug therapy, cell therapy, gene therapy and olfactory training.

SIRT6 inhibits metastasis by suppressing SNAIL expression in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with severe local invasion and early distant metastasis. SIRT6 serves as a critical modulator of the development and metastasis of multiple types of cancer; however, the roles and underlying mechanisms of SIRT6 in regulating NPC metastasis remain largely unknown. Here, the expression of SIRT6 in high metastatic 5-8F cells and low metastatic 6-10B cells was analyzed. SIRT6 expression was found to be negatively associated with the metastatic capability of NPC cells. Moreover, we identified that SIRT6 inhibited NPC cell metastasis through suppression of SNAIL expression. Mechanistically, we demonstrated that SIRT6 interacted with transcription factor p65 (NF-kB subunit) and deacetylated histone H3 lysine 9 (H3K9) and lysine 56 (H3K56) at the promoter of SNAIL, leading to reduced transcription of SNAIL. In summary, SIRT6 functions as a metastasis suppressor in NPC cells through epigenetic regulation of SNAIL gene expression.

High pretreatment platelet-to-lymphocyte ratio is related to poor prognosis in the squamous cell carcinoma of the larynx and hypopharynx in male patients.

BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.