Refining feasibility assessment of endoscopic ear surgery: a radiomics model utilizing machine learning on external auditory canal CT scans.

BACKGROUND: Feasibility assessment of endoscopic ear surgery (EES) relies solely on subjective evaluation by surgeons. OBJECTIVE: Extracting radiomic features from preoperative CT images of the external auditory canal, we aim to classify EES patients into easy and difficult groups and improve accuracy in determining surgery feasibility. METHODS: 85 patients' external auditory canal CT scans were collected and 139 radiomic features were extracted using PyRadiomics. The most relevant features were selected and three machine learning algorithms (logistic regression, support vector machine, and random forest) were compared using K-fold cross-validation (k = 5) to predict surgical feasibility. RESULTS: The best-performing machine learning model, the support vector machine (SVM), was selected to predict the difficulty of EES. The proposed model achieved a high accuracy of 86.5%, and F1 score of 84.6%. The area under the ROC curve was 0.93, indicating good discriminatory power. CONCLUSIONS AND SIGNIFICANCE: The proposed machine learning model provides a reliable and accurate method for classifying patients undergoing otologic surgery based on preoperative imaging data. The model can help clinicians to better prepare for challenging surgical cases and optimize treatment plans for individual patients.

Identifying key genes and small molecule compounds for nasopharyngeal carcinoma by various bioinformatic analysis.

ABSTRACT: Nasopharyngeal carcinoma (NPC) is one of the most prevalent head and neck cancer in southeast Asia. It is necessary to proceed further studies on the mechanism of occurrence and development of NPC.In this study, we employed the microarray dataset GSE12452 and GSE53819 including 28 normal samples and 49 nasopharyngeal carcinoma samples downloaded from the Gene Expression Omnibus(GEO) to analysis. R software, STRING, CMap, and various databases were used to screen differentially expressed genes (DEGs), construct the protein-protein interaction (PPI) network, and proceed small molecule compounds analysis, among others.Totally, 424 DEGs were selected from the dataset. DEGs were mainly enriched in extracellular matrix organization, cilium organization, PI3K-Akt signaling pathway, collagen-containing extracellular matrix, and extracellular matrix-receptor interaction, among others. Top 10 upregulated and top 10 downregulated hub genes were identified as hub DEGs. Piperlongumine, apigenin, menadione, 1,4-chrysenequinone, and chrysin were identified as potential drugs to prevent and treat NPC. Besides, the effect of genes CDK1, CDC45, RSPH4A, and ZMYND10 on survival of NPC was validated in GEPIA database.The data revealed novel aberrantly expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Although further studies needed, the results demonstrated that the expression levels of CDK1, CDC45, RSPH4A, and ZMYND10 probably affected survival of NPC patients.

Low expression of CIP4 in predicting worse overall survival: A potential biomarker for laryngeal cancer.

Previous reports indicate that Cdc42-interacting protein-4 (CIP4) has previously been reported to plays an important role in the progression of various cancers. However, its correlation with laryngeal cancer (LC) remains unreported. Data from TCGA and GEO databases were used to evaluate the role of CIP4 in LC. Based on GEO and TCGA datasets, we analyzed the differences in CIP4 expression between normal and tumor samples. The Wilcoxon signed-rank test was used to analyze the relationship between clinical features and CIP4. Cox regression and the Kaplan-Meier analyses were used to identify the clinical characteristics associated with the overall survival. Also, the GEPIA database was used to confirm the relationship between CIP4 and overall survival. Lastly, Gene Set Enrichment Analysis (GSEA) was performed based on the TCGA dataset. CIP4 expression in LC was significantly associated with gender and tumor stage (p-values<0.05). Similar to GEPIA validation, Kaplan-Meier survival analysis demonstrated that LC with CIP4-low exhibited a worse prognosis than that with CIP4-high. Univariate analysis revealed that CIP4-high significantly correlated with better overall survival (HR: 0.522, 95% CI: 0.293-0.830, P = 0.026). Besides, multivariate analysis revealed that CIP4 remained independently associated with the overall survival (HR: 0.61, 95% CI: 0.326-0.912, P = 0.012). GSEA showed that the p53, WNT signaling, TGF-ß signaling pathways, etc. were enriched in a phenotype high CIP4 expression. In summary, the CIP4 gene is a potential prognostic molecular marker for patients diagnosed with laryngeal cancer. Moreover, the p53, WNT signaling, and TGF-ß signaling pathways are potentially associated with CIP4 in LC.

Prognostic values and clinical relationship of TYK2 in laryngeal squamous cell cancer.

ABSTRACT: Laryngeal squamous cell cancer (LSCC) is the second most common head and neck cancer with the increasing mortality. The tyrosine kinase 2 (TYK2) has previously been reported to play an important role in various cancers excepting LSCC. We used available data from the cancer genome atlas program (TCGA), gene expression omnibus, and gene expression profiling interactive analysis (GEPIA) to evaluate the role of TYK2 in LSCC.The difference of TYK2 expression level between normal and tumor samples was analyzed based on TCGA, gene expression omnibus, and GEPIA databases. The relationship between clinical features and TYK2 were analyzed using the Wilcoxon signed-rank test. We applied Cox regression and the Kaplan-Meier method to finding which clinical characteristics is associated with overall survival. Also, we used GEPIA database to validate the relationship between TYK2 and overall survival. At last, we performed gene set enrichment analysis based on TCGA data set.The expression level of TYK2 in LSCC was significantly associated with gender, lymph node status and metastasis (P-values <.05). Kaplan-Meier survival analysis, as same as GEPIA validation, demonstrated that LSCC with TYK2-low had a worse prognosis than that with TYK2-high. The univariate analysis showed that TYK2-high correlated significantly with a better overall survival (hazard ratio: 0.351, 95% confidence interval: 0.194-0.637, P < .001). The multivariate analysis revealed that TYK2 remained independently associated with overall survival (hazard ratio: 0.36, 95% confidence interval: 0.185-0.699, P = .003). Gene set enrichment analysis shows that Janus kinases-STAT signaling pathway, p53 signalling pathway and natural killer cell mediated cytotoxicity, etc are enriched in TYK2 high expression phenotype.Gene TYK2 may be a potential prognostic molecular marker for LSCC. Moreover, the Janus kinases-STAT signaling pathway and p53 signaling pathway are probably the key pathway associated with TYK2 in LC.

Which treatment is better than concurrent chemoradiotherapy about survival for stage III or IV locally advanced nasopharyngeal carcinoma? An updated Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: To speculate whether induction chemotherapy (IC) or adjuvant chemotherapy (AC) with concurrent chemoradiotherapy (CCRT) could obtain better survival benefit for stage III or IV locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Only randomized controlled trials were incorporated. There were five treatments (CCRT, IC + CCRT, CCRT + AC, IC + RT and RT alone) recruited for analysis. Overall survival (OS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) with a hazard ratio (HR) were selected as endpoints. First of all, we performed a traditional meta-analysis and subsequently conducted network meta-analysis based on the Bayesian method. RESULTS: Totally, 15 studies, including 6182 patients, were incorporated for analysis. There was a statistically significant benefits in favor of IC + CCRT, compared with CCRT alone, for OS [HR = 0.75, 95% CI = 0.63-0.89], LRFS [HR = 0.70, 95% CI = 0.56-0.86], and DMFS [HR = 0.65, 95% CI = 0.54-0.78]. What's more, we did not observed any significant differences between CCRT + AC and CCRT alone for all the endpoints. Unsurprisingly, it was RT alone that demonstrate the poorest survival benefit. Strange to say, survival benefit, between IC + CCRT and IC + RT, or between IC + CCRT and CCRT + AC, did not significantly exist. CONCLUSION: Induction chemotherapy IC + CCRT provided better survival benefit than CCRT alone. CCRT + AC failed to increase survival benefit significantly compared to CCRT alone. More research about comparing IC + CCRT with IC + RT or CCRT + AC are needed.

Impact of prior cancer history on the survival of patients with larynx cancer.

BACKGROUND: Patients with a prior history of cancer are commonly excluded from clinical trial. Increasing number of studies implied that a prior cancer did not adversely affect the clinical outcome among various types of cancer patients. However, the impact of prior cancer on survival of larynx cancer patients remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with larynx cancer. METHODS: Patients with larynx cancer as the first or second primary malignancy diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis. RESULTS: A total of 24,812 eligible patients with larynx cancer were included in the study, wherein a total of 2436 patients (9.8%) had a prior history of cancer. Prostate (36%), lung and bronchus (10%), urinary bladder (7%), and breast (6%) were the most common types of prior cancer. A prior cancer history served as a risk factor for overall survival (AHR =1.30; 95% CI [1.21-1.41]; P < 0.001) but a protective factor for cancer-specific mortality (AHR = 0.83; 95% CI [0.72-0.94]; P = 0.004) in comparison with those without prior cancer. The subgroup analysis showed that a prior history of cancer adversely affected overall survival of patients with larynx cancer in most subgroups stratified by timing and types of prior cancer, as well as by different clinicopathologic features. CONCLUSION: Our study indicated an adverse survival impact of a prior history of cancer on patients with larynx cancer. Except for a few particular prior cancer, clinical trials should be considered prudently for laryngeal cancer patients with prior cancers.

Downregulation of cancer stem cell properties via mTOR signaling pathway inhibition by rapamycin in nasopharyngeal carcinoma.

Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits cancer cell proliferation and tumor formation, including in nasopharyngeal carcinoma (NPC), which we proved in a previous study. However, whether rapamycin affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we found regions of CD44-positive cancer cells co-expressing the stem cell biomarker OCT4, suggesting the presence of CSCs. Following this, we used double-label immunohistochemistry to identify whether the mTOR signaling pathway was activated in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC cells and secondary tumors in BALB/c nude mice. Interestingly, we found that rapamycin inhibited mTOR signaling in addition to simultaneously downregulating the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor size and weight both in vitro and in vivo. Collectively, we confirmed for the first time that CSC properties are reduced and invasion potential is restrained in response to mTOR signaling inhibition in NPC. This evidence indicates that the targeted inhibition of CSC properties may provide a novel strategy to treat cancer.

Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium.

Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma.