The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. High-throughput sequencing data have laid a solid foundation for identifying genes related to cancer prognosis, but a gene marker is needed to predict clinical outcomes in HNSCC. In our study, we downloaded RNA Seq, single nucleotide polymorphism, copy number variation, and clinical follow-up data from TCGA. The samples were randomly divided into training and test. In the training set, we screened genes and used random forests for feature selection. Gene-related prognostic models were established and validated in a test set and GEO verification set. Six genes (PEX11A, NLRP2, SERPINE1, UPK, CTTN, D2HGDH) were ultimately obtained through random forest feature selection. Cox regression analysis confirmed the 6-gene signature is an independent prognostic factor in HNSCC patients. This signature effectively stratified samples in the training, test, and external verification sets (P < 0.01). The 5-year survival AUC in the training and verification sets was greater than 0.74. Thus, we have constructed a 6-gene signature as a new prognostic marker for predicting survival of HNSCC patients.
Head and neck squamous cell carcinoma (HNSCC) is a common malignant cancer that accounts for 5–10% of all cancers. This study aimed to identify essential genes associated with the prognosis of HNSCC and construct a powerful prognostic model for the risk assessment of HNSCC. RNAseq expression profile data for the patients with HNSCC were obtained from the TCGA database (GEO). A total of 500 samples with full clinical following-up were randomly divided into a training set and a validation set. The training set was used to screen for differentially expressed lncRNAs. Single-factor survival analysis was performed to obtain lncRNAs that associated with prognosis. A robust likelihood-based survival model was constructed to identify the lncRNAs that are essential for the prognosis of HNSCC. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to serve as the final signature lncRNAs for prognosis. Finally, the prognostic effect of the signature lncRNAs was tested by multi-factor survival analysis and a scoring model for the prognosis of HNSCC was constructed. Moreover, the results of the validation set and the relative expression levels of the signature lncRNAs in the tumour and the adjacent tissue were consistent with the results of the training set. The 5 lncRNAs were distributed among 3 expression modules. Further KEGG pathway enrichment analysis showed that these 3 co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease. Therefore, we proposed that the 5 validated lncRNAs can be used to predict the prognosis of HNSCC patients and can be applied in postoperative treatment and follow-up.
To date, no effective therapeutic treatments have been developed for hypopharyngeal squamous cell carcinoma (HPSCC), a disease that has a five-year survival rate of approximately 31% because of its late diagnosis and aggressive nature. Despite recent improvements in diagnostic methods, there are no effective measures to prevent or detect HPSCC in an early stage. The goal of the current study was to identify molecular biomarkers and networks that can facilitate the speedy identification of HPSCC patients who could benefit from individualized treatment. Isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed with two-dimensional liquid chromatography-tandem mass spectrometry to identify quantitatively the differentially expressed proteins among three types of HPSCC disease stages. The iTRAQ results were evaluated by literature searches and western blot analysis. For example, FUBP1, one of 412 proteins with significantly altered expression profiles, was confirmed to have elevated expression in fresh HPSCC tissues. Integrin-mediated cell matrix adhesion and actin filament-inducing cytoskeleton remodeling were the cellular events that were the most relevant to HPSCC tumorigenesis and the metastatic process. The construction of transcriptional regulation networks led to the identification of key transcriptional regulators of tumor development and lymph node metastasis of HPSCC, including Sp1, c-Myc and p53. Additionally, our study indicated that the interactions among Sp1, c-Myc and p53 may play vital roles in the carcinogenesis and metastasis of HPSCC.
Papillary thyroid cancer (PTC) accounts for the majority of malignant thyroid tumors. Recently, several microRNA (miRNA) expression profiling studies have used bioinformatics to suggest miRNA signatures as potential prognostic biomarkers in various malignancies. However, a prognostic miRNA biomarker has not yet been established for PTC. The aim of the present study was to identify miRNAs with prognostic value for the overall survival (OS) of patients with PTC by analyzing high‐throughput miRNA data and their associated clinical characteristics downloaded from The Cancer Genome Atlas database. From our dataset, 150 differentially expressed miRNAs were identified between tumor and nontumor samples; of these miRNAs, 118 were upregulated and 32 were downregulated. Among the 150 differentially expressed miRNAs, a four miRNA signature was identified that reliably predicts OS in patients with PTC. This miRNA signature was able to classify patients into a high‐risk group and a low‐risk group with a significant difference in OS (P < .01). The prognostic value of the signature was validated in a testing set ( P < .01). The four miRNA signature was an independent prognostic predictor according to the multivariate analysis and demonstrated good performance in predicting 5‐year disease survival with an area under the receiver operating characteristic curve area under the curve (AUC) score of 0.886. Thus, this signature may serve as a novel biomarker for predicting the survival of patients with PTC.
Abstract. Development of metastasis is a major cause of death for squamous cell carcinoma of the head and neck (sccHn) patients. epithelial to mesenchymal transition (eMt) is now regarded as a correlate of tumor metastasis. given that transforming growth factor-β1 (tgF-β1) is an important inducer of eMt, we examined the effects of tgF-β1 on the human sccHn cell line tu686. We found that tgF-β1 mediated cell morphological changes. phasecontrast microscopy revealed a loss of the adherent phenotype with cellular elongation, decrease in cell-to-cell contact, and the induction of a fibroblast-like state. Western blotting and reverse transcriptase-polymerase chain reaction (rt-pcr) analysis demonstrated that tgF-β1 could induce down-regulation of the epithelial marker e-cadherin and up-regulation of the mesenchymal marker vimentin in tu686 cells in a concentration-and time-dependent manner. Woundhealing and transwell invasion assay indicated that tgF-β1 promoted tu686 cell migration and invasion dramatically. In addition, these changes were mediated via canonical tgF-β/ smad signaling with concomitant up-regulation of phosphorylated smad2. smad2 rnAi abrogated both expression and functional effects of tgF-β1 on tu686 cells. In conclusion, the present study demonstrates that tgF-β1 could induce EMT in the SCCHN cell line via the TGF-β/Smad signaling pathway. More importantly, a cell model for eMt was established, which is valuable for future studies on the metastasis of sccHn.
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