Identification of Significant Secreted or Membrane-Located Proteins in Laryngeal Squamous Cell Carcinoma.

Background: This study is aimed at investigating the expressions and prognostic values of secreted or membrane-located proteins (SMPs) in laryngeal squamous cell carcinoma (LSCC). The correlations between the expressions of SMPs and immune cells' infiltrations were also investigated. Methods: The expression data of normal laryngeal and LSCC samples were obtained from the TCGA and GEO datasets. The differentially expressed SMPs were identified, and their prognostic values were analyzed. The biological functions of differentially expressed and worse-survival-related SMPs were explored. LASSO regression, Cox multivariate analysis, and nomogram were used to construct a model to predict the survival. Then, the infiltrations of the 24 immune cell populations were calculated using the GSVA method, and the correlations between the expression of SMPs and the immune infiltration were investigated. Results: 122 samples (12 normal and 120 LSCC) of the TCGA database and 114 samples (57 normal and 57 LSCC) of GSE127165 were included. We identified that 138 SMPs were significantly upregulated in LSCC samples of both the TCGA and GEO datasets, among which 52 SMPs were significantly correlated with worse survival. GO and KEGG analyses revealed those 52 SMPs significantly participate in tumor microenvironment and immune cells' communication. Nine of 52 SMPs (ABCC5, ATP1B3, CLEC11A, FLNA, FSTL3, MMP1, NME1, OAS3, and PHLDB2) were included in the nomogram to effectively and accurately predict the LSCC patients' survival. The expressions of most SMPs, such as MMP1 and FSTL3, were significantly positively correlated with the immune infiltration of LSCC. Conclusions: In this study, the expression, prognostic values, and correlations with immune infiltration of SMPs were analyzed in LSCC samples. Our analyses identified several significant SMPs differentially expressed between normal laryngeal and LSCC samples, correlated with worse survival, and related to the immune infiltration.

Identification and Validation of Immune Infiltration Phenotypes in Laryngeal Squamous Cell Carcinoma by Integrative Multi-Omics Analysis.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the world's most common head and neck cancer. However, the immune infiltration phenotypes of LSCC have not been well investigated. Methods: The multi-omics data of LSCC were obtained from the TCGA (n=111) and GEO (n=57) datasets. The infiltrations of the 24 immune cell populations were calculated using the GSVA method. Then LSCC samples with different immune cell infiltrating patterns were clustered, and the multi-omics differences were investigated. Results: Patients were clustered into the high-infiltration and low-infiltration groups. The infiltration scores of most immune cells were higher in the high-infiltration group. Patients with high-infiltration phenotype have high N and TNM stages but better survival, as well as less mutated COL11A1 and MUC17. Common targets of immunotherapies such as PD1, PDL1, LAG3, and CTLA4 were significantly up-regulated in the high-infiltration group. The differentially expressed genes were mainly enriched in several immune-related GOs and KEGG pathways. Based on the genes, miRNAs, and lncRNAs differentially expressed in both the TCGA and GEO cohorts, we built a ceRNA network, in which BTN3A1, CCR1, miR-149-5p, and so on, located at the center. A predictive model was also constructed to calculate a patient's immune infiltration phenotype using 16 genes' expression values, showing excellent accuracy and specificity in the TCGA and GEO cohorts. Conclusions: In this study, the immune infiltration phenotypes of LSCC and the corresponding multi-omics differences were explored. Our model might be valuable to predicting immunotherapy's outcome.

Comparison of outcomes between patients with de-novo sinonasal squamous cell carcinoma vs malignant transformations from inverted papillomas.

BACKGROUND: The survival difference between de-novo sinonasal squamous cell carcinoma (DN-SNSCC) and SCC arising from inverted papillomas (IPs) is unclear. The purpose of this study was to compare the outcomes between DN-SNSCC and IP-transformed SNSCC (IP-SNSCC) patients. METHODS: In this retrospective review, we compared IP-SNSCC and DN-SNSCC cases from the Eye and ENT Hospital of Fudan University from 2010 to 2017. A total of 162 patients (39 IP-SNSCC and 123 DN-SNSCC) were included in our study. Demographics, tumor characteristics, treatment, and clinical outcomes were analyzed. RESULTS: The median follow-up time in all cohorts was 56 (range, 5-109) months. There was no difference in age, sex, smoking history, alcohol consumption, tumor primary site, or disease stage between the IP-SNSCC and DN-SNSCC patients. We also did not find significant differences in overall survival and disease-free survival between IP-SNSCC and DN-SNSCC patients (p = 0.584 and p = 0.238, respectively). The 5-year local failure rate was 52.8% for IP-SNSCC patients, which was significantly higher than for those with DN-SNSCC (31.9%; p = 0.013). The 5-year nodal failure rate was 19.0% for IP-SNSCC patients and 8.5% for DN-SNSCC patients (p = 0.211). The 5-year distant metastasis rate was 8.0% for IP-SNSCC patients and 16.1% for DN-SNSCC patients (p = 0.318). CONCLUSION: IP-SNSCC and DN-SNSCC patients have similar survival outcomes. IP-SNSCC seems to have exhibited a higher local failure rate in our study. We believe that IP-SNSCC is a highly aggressive disease that requires radical treatment. Prophylactic neck treatment should not be omitted in a subset of IP-SNSCC patients.

Development and validation of a nomogram for prognosis of sinonasal squamous cell carcinoma.

BACKGROUND: Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with varied outcomes. The aim of this study was to develop a nomogram for predicting survival of patients with SNSCC. METHODS: From the Surveillance, Epidemiology, and End Results database, we identified 1766 patients diagnosed with SNSCC between 2004 and 2015. Patients were randomly separated into a training set and a validation set in 4:1 ratio. An external validation was also performed by a set of 74 SNSCC patients who had been treated in our department. We used the training set to build a nomogram based on stratified multivariable Cox proportional hazard models for predicting overall survival. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index and calibration curve. RESULTS: Based on 1412 cases of the training cohort, our Cox regression analysis revealed that age, marital status, primary site, differentiation, T stage, N classification, M stage, and treatment modalities were associated with overall survival. A nomogram was established based on the results of multivariate analysis. The C-index values of the nomogram for predicting survival were superior to those of the tumor-node-metastasis staging system (0.745 vs 0.679 in the training cohort, 0.752 vs 0.656 in the validation set, and 0.678 vs 0.596 in the external validation set). The calibration plots demonstrated good consistency between the predicted and observed results. CONCLUSION: We have developed a nomogram to accurately predict the clinical outcomes of SNSCC patients. This model was effective and can help clinicians to improve patient counseling.

Dosimetric parameters associated with conductive or sensorineural hearing loss 5 years after intensity-modulated radiation therapy in nasopharyngeal carcinoma.

BACKGROUND: Most previous studies are separate dosimetric analyses of conductive or sensorineural hearing loss, and they are not conducive to a comprehensive assessment of auditory radiation damage. AIMS/OBJECTIVES: Our study aimed to evaluate the long-term incidence of sensorineural hearing loss (SNHL) or conductive hearing loss (CHL) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiation therapy (IMRT), and to investigate the relationship between SNHL or CHL and patient factors, treatment-related factors, and radiation dose parameters. MATERIAL AND METHODS: Seventy patients (117 ears) with NPC, who were also treated with IMRT in our hospital from 2006 to 2014, were retrospectively analyzed. Radiation doses to the Eustachian tube (ET), middle ear (ME), cochlear (Co), and internal auditory canal (IAC) were assessed. Pure tone audiometry and impedance audiometry were performed before and during the follow-up period. The relationships between low-frequencies (0.5-2 kHz) or high-frequency (4 kHz) SNHL/CHL and radiotherapy dose parameters were analyzed. RESULTS: Of the 117 ears studied, 7.69% had low-frequency SNHL, 35.9% had high-frequency SNHL, 23.93% had low-frequency CHL, and 18.80% had high-frequency CHL. The incidence of high-frequency CHL was higher in the T4 group than in the T (1-3) group (p < .05). When IAC Dmax > 42.13 Gy or IAC Dmean > 32.71 Gy, the risk of high-frequency SNHL increased in NPC patients. When ME Dmax > 44.27 Gy, ME Dmean > 29.28 Gy, or ET Dmax > 57.23 Gy, the risk of high-frequency CHL in NPC patients increased. CONCLUSIONS AND SIGNIFICANCE: SNHL and CHL remain common ear complications after IMRT for NPC. IAC Dmax, IAC Dmean, ME Dmax, ME Dmean, and ET Dmax all need to be carefully considered during the IMRT treatment protocol.

A20 inactivation in ocular adnexal MALT lymphoma.

Recent studies showed A20 inactivation by deletion, mutation and promoter methylation in ocular adnexal mucosa-associated lymphoid tissue lymphoma. However, the incidences of A20 abnormalities and their clinical impact remain for the most part unknown. It is also unknown whether ABIN-1 and ABIN-2, the components of the A20 NF-κB inhibitor complex, are inactivated by genetic changes in ocular adnexal mucosa-associated lymphoid tissue lymphoma. A total of 105 cases were investigated for A20 mutation/deletion, ABIN-1/2 mutation, MALT1 and IGH involved translocation. Somatic mutation was seen frequently in A20 (28.6%) but rarely in ABIN-1 (1%) and ABIN-2 (1%). A20 mutations were significantly associated with A20 heterozygous deletion, and both were mutually exclusive from the MALT1 or IGH involved translocations. A20 mutation/deletion was also significantly associated with increased expression of the NF-κB target genes CCR2, TLR6 and BCL2. The cases with A20 mutation/deletion required significantly higher radiation dosages to achieve complete remission than those without these abnormalities.

[Synthetic treatment of malignant tumor of nasal cavity and sinus based-on modern technique radiotherapy].

OBJECTIVE: To evaluate the therapeutic effect of malignant tumor of nasal cavity and sinus that based on modern radiotherapy. METHOD: Two hundred cases of malignant tumor of nasal cavity and sinus were retrospectively analyzed from 2004 to 2007. All the cases were location by CT simulator system and were treated with three dimensional conformal radiotherapy. RESULT: Among malignant tumor of nasal cavity and sinus, the incidence for locations was nasal cavity > maxillary sinus > ethmoid sinus > sphenoid sinus; the incidence for the type of pathology was squamous cell carcinoma > adenocarcinoma > olfactory neuroblastoma and olfactory esthesioneuroepithelioma > malignant melanoma > rhabdomyosarcoma; the incidence for general metastasis was rhabdomyosarcoma > malignant melanoma > adenocarcinoma, inverted papilloma and malignant changes > squamous cell carcinoma, olfactory neuroblastoma and olfactory esthesioneuroepithelioma. No severe radiation-related complication were found. CONCLUSION: Clinical stage, pathological type were the important factors effecting the prognosis of patients with malignant tumor of nasal cavity and sinus. Three dimensional conformal radiotherapy based on CT simulator system could improve therapeutic effect and protect the normal tissue very well.

[Prognostic value of synchronized detection of microvascular and lymph vessel density in nasopharyngeal carcinoma].

OBJECTIVE: To investigate the distribution patterns of microvascular density(MVD) and lymph vessel density (LVD) in nasopharyngeal carcinoma, and to discuss their relationships with tumor recurrence-metastasis and prognosis. METHOD: One hundred and six patients with pathologically proved nasopharyngeal carcinoma were included in this study. Immunostainings for the vascular endothelial marker CD34 and the lymph vessel marker D2-40 were performed. The microvascular and lymph vessels within the tumor and the peritumoral area were respectively quantified with computer assisted morphometric analysis. RESULT: Both microvascular and lymph vessels were positive in the specimen of 106 nasopharyngeal carcinoma patients, with MVD and LVD higher in the peritumoral area than in the tumor. Univariate analysis showed that intra-tumor MVD,intra-tumor and peritumor LVD were correlated with nasopharyngeal carcinoma recurrence-metastasis (P < 0.05), while no significant correlation was found between tumor recurrence-metastasis and age, gender, T stage, lymph node stage, clinical stage and peritumor MVD (P > 0.05). Multivariate analysis demonstrated that intra-tumor MVD and peri-tumor LVD were two independent risk factors of nasopharyngeal carcinoma recurrence-metastasis. Higher intra-tumor MVD was associated with adverse prognosis of nasopharyngeal carcinoma (P < 0.05). CONCLUSION: High MVD and LVD may be of significance in predicting poor prognosis in patients with nasopharyngeal carcinoma. Intra-tumor and peri-tumor microvessels may play different roles in the tumor recurrence and metastasis. Intra-tumor MVD and peri-tumor LVD should be the therapeutic targets in the nasopharyngeal carcinoma.