Background: Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intent surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. Methods: A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in this study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Results: Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models’ concordance. The C-index of the nomogram was 0.73 (0.68-0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) was 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had a larger net benefit than the TNM stage. Conclusion: A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.
Background Recurrence remains a major obstacle to long-term survival of laryngeal squamous cell carcinoma (LSCC). We conducted a genome-wide integrated analysis of methylation and the transcriptome to establish methylation-driven genes prognostic signature (MDGPS) to precisely predict recurrence probability and optimize therapeutic strategies for LSCC. Methods LSCC DNA methylation datasets and RNA sequencing (RNA-seq) dataset were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed a recurrence-free survival (RFS)-related MDGPS. The predictive accuracy and clinical value of the MDGPS were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of MDGPS was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs, the candidate small molecules for LSCC were screen out by the CMap database. To strengthen the bioinformatics analysis results, 30 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH). Results A total of 88 DNA MDGs were identified, and five RFS-related MDGs (LINC01354, CCDC8, PHYHD1, MAGEB2 and ZNF732) were chosen to construct a MDGPS. The MDGPS can effectively divide patients into high-risk and low-risk group, with the area under curve (AUC) of 0.738 (5-year RFS) and AUC of 0.74 (3-year RFS). Stratification analysis affirmed that the MDGPS was still a significant statistical prognostic model in subsets of patients with different clinical variables. Multivariate Cox regression analysis indicated the efficacy of MDGPS appears independent of other clinicopathological characteristics. In terms of predictive capacity and clinical usefulness, the MDGPS was superior to traditional TNM stage. Additionally, the MDGPS was confirmed in external LSCC cohorts from GEO. CMap matched the 9 most significant small molecules as promising therapeutic drugs to reverse the LSCC gene expression. Finally, CISH analysis in 30 LSCC tissues and paired adjacent normal tissues revealed that MAGEB2 has significantly higher expression of LSCC compared to adjacent non-neoplastic tissues; LINC01354, CCDC8, PHYHD1, and ZNF732 have significantly lower expression of LSCC compared to adjacent non-neoplastic tissues, which were in line with bioinformatics analysis results. Conclusion A MDGPS, with five DNA MDGs, was identified and validated in LSCC patients by combining transcriptome and methylation datasets analysis. Compared TNM stage alone, it generates more accurate estimations of the recurrence prediction and maybe offer novel research directions and prospects for individualized treatment of patients with LSCC.
Background Long non‐coding RNA myocardial infarction associated transcript (MIAT) has been suspected to be associated with poor prognosis in several malignancies. This study aims to investigate the association between MIAT expression levels and prognosis of tongue squamous cell carcinoma (TSCC). Materials and Methods Expressions of MIAT in TSCC specimens, corresponding adjacent non‐neoplastic tongue tissues, and serums collected from 116 TSCC patients were detected by Quantitative Real‐Time PCR. Then, these patients were followed up for 12 months after discharge. MIAT was suppressed and upregulated in TSCC cells, and then cell invasion and epithelial‐mesenchymal transition (EMT) markers were analyzed. Results Myocardial infarction associated transcript expression level in TSCC specimen was upregulated compared to adjacent non‐neoplastic tongue tissue and had a significant positive association with its level in serum. MIAT levels in both TSCC specimen and serum were correlated with cervical lymph node metastasis and histological grading of TSCC patients. Results of survival analysis showed that high expression levels of MIAT in both TSCC tissues and serums indicated higher mortality and shorter survival time of TSCC patients. Receiver operating characteristic curve analysis showed that there was no significant difference between MIAT in TSCC specimen and serum to differentiate death and non‐death of TSCC patients. In vitro study showed that MIAT could induce invasion of TSCC cells by regulating expressions of EMT markers through activation of Wnt/β‐catenin signaling pathway. Conclusion Upregulated MIAT promoted EMT of TSCC cells through activation of Wnt/β‐catenin signaling pathway and indicated a poor prognosis of TSCC, which may provide us a non‐invasive approach to evaluate the prognosis of TSCC.
Background: Due to a wide variation of tumor behavior, prediction of survival in laryngeal squamous cell carcinoma (LSCC) patients received curative-intend surgery is an important but formidable challenge. We attempted to establish a nomogram to precisely predict survival probability in LSCC patients. Methods: A total of 369 consecutive LSCC patients underwent curative resection between 2008 and 2012 at Hunan Province Cancer Hospital were included in this study. Subsequently, 369 LSCC patients were assigned to a training set (N=261) and a validation set (N=108) at random. On the basis of multivariable Cox regression analysis results, we developed a nomogram. The predictive accuracy and discriminative ability of the nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to estimate clinical usefulness of our nomogram. Results: Six independent parameters to predict prognosis were age, pack years, N-stage, lymph node ratio (LNR), anemia and albumin, which were all assembled into the nomogram. The calibration curve verified excellent models’ concordance. The C-index of the nomogram was 0.73 (0.68-0.78), and the area under curve (AUC) of nomogram in predicting overall survival (OS) were 0.766, which were significantly higher than traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage.Conclusion: A risk prediction nomogram for patients with LSCC, incorporating easily assessable clinicopathologic factors, generates more precise estimations of the survival probability when compared TNM stage alone, but still need additional data before being used in clinical application.
Background: Epigenetic alterations, such as DNA methylation patterns, yield an important role in the initiation, progression and prognosis of laryngeal squamous cell carcinoma (LSCC). We performed a genome-wide integrated analysis of methylation and the transcriptome to establish epigenetic signature to improve the accuracy of survival prediction and optimize therapeutic strategies for LSCC.Methods: LSCC DNA methylation datasets and RNA sequencing (RNA-seq) datasets were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed an epigenetic signature. The predictive accuracy and clinical value of the epigenetic signature were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of the epigenetic signature was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs of epigenetic signature, the candidate small molecules for LSCC were screen out by the CMap database.Results: A total of 88 DNA MDGs were identified, five of which (MAGEB2, SUSD1, ZNF382, ZNF418 and ZNF732) were chosen to construct an epigenetic signature. The epigenetic signature can effectively divide patients into high-risk and low-risk group, with the area under curve (AUC) of 0.8 (5-year OS) and AUC of 0.745 (3-year OS). Stratification analysis affirmed that the epigenetic signature was still a significant statistical prognostic model in subsets of patients with different clinical variables. Multivariate Cox regression analysis indicated the efficacy of epigenetic signature appears independent of other clinicopathological characteristics. In terms of predictive capacity and clinical usefulness, the epigenetic signature was superior to traditional TNM stage. Additionally, the epigenetic signature was confirmed in external LSCC cohorts from GEO. Finally, CMap matched the 10 most significant small molecules as promising therapeutic drugs to reverse the LSCC gene expression.Conclusion: An epigenetic signature, with five DNA MDGs, was identified and validated in LSCC patients by integrating multidimensional genomic data. Compared TNM stage alone, it generates more accurate estimations of the survival probability and maybe offer novel research directions and prospects for individualized treatment of patients with LSCC.
Background Dosage-optimized multimodal radiotherapies that are safe for head and neck cancer patients are desirable. In this study, we investigated tissue tolerance to varying doses of external beam radiotherapy (EBRT) combined with low-dose rate brachytherapy in the neck of a rabbit model. Methods Twenty rabbits were used in the four test groups (five each) with iodine-125 seeds implanted in the neck treated with EBRT in four doses at 50, 40, 30 and 20 Gy each. Twelve rabbits for three control groups (four each). Three months after implantation, all rabbits were euthanized, and target tissues were collected. Analyses included seed implantation assessment, histopathological evaluation, immunohistochemistry staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, electron microscopy and statistics with the SPSS software. Results Five rabbits died in the four test groups, and three rabbits died in the three control groups (one per group), which showed no significant difference by survival analysis. The calculated minimum peripheral dose was 17.6 Gy, the maximum dose near the seed was 1812.5 Gy, the D90 was 34.5 Gy and the mean dose was 124.5 Gy. In all groups that received radiation, apoptosis occurred primarily in the esophageal mucosa and corresponded to the dose of radiation; a higher dose caused a greater apoptosis, with significant difference between groups (P < 0.05). Electron microscopy of carotid arteries revealed that endothelial cells were swollen and some were shed from basement membrane, but no other noticeable tissue damages. Conclusions Limited EBRT at maximal dose (50 Gy) combined with the brachytherapy interstitially applied to the neck was tolerated well in the rabbit model.
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