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A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma.

ABSTRACT: Molecular methods for predicting prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are urgently needed, considering its high recurrence rate and tendency for metastasis. The present study investigated the genetic basis of variations in gene expression associated with poor prognosis in OSCC using Affymetrix SNP 6.0 and Affymetrix GeneChip Human Gene 1.0 ST arrays. We identified recurrent DNA amplifications scattered from 8q22.2 to 8q24.3 in 112 OSCC specimens. These amplicons demonstrated significant associations with increased incidence of extracapsular spread, development of second primary malignancies, and poor survival. Fluorescence in situ hybridization, in a validation panel consisting of 295 cases, confirmed these associations. Assessment of the effects of copy number variations (CNVs) on genome-wide variations in gene expression identified a total of 85 CNV-associated transcripts enriched in the MYC-centered regulatory network. Twenty-four transcripts associated with increased risk of second primary malignancies, tumor relapse, and poor survival. Besides MYC itself, a novel dysregulated MYC module plays a key role in OSCC carcinogenesis. This study identified a candidate molecular signature associated with poor prognosis in OSCC patients, which may ultimately facilitate patient-tailored selection of therapeutic strategies.

SUBMITTER: Peng CH

PROVIDER: S-EPMC3154947 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma.

Peng Chien-Hua CH Liao Chun-Ta CT Peng Shih-Chi SC Chen Yin-Ju YJ Cheng Ann-Joy AJ Juang Jyh-Lyh JL Tsai Chi-Ying CY Chen Tse-Ching TC Chuang Yung-Jen YJ Tang Chuan-Yi CY Hsieh Wen-Ping WP Yen Tzu-Chen TC

PloS one 20110811 8

Molecular methods for predicting prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are urgently needed, considering its high recurrence rate and tendency for metastasis. The present study investigated the genetic basis of variations in gene expression associated with poor prognosis in OSCC using Affymetrix SNP 6.0 and Affymetrix GeneChip Human Gene 1.0 ST arrays. We identified recurrent DNA amplifications scattered from 8q22.2 to 8q24.3 in 112 OSCC specimens. These amplicons ...[more]

PMID: 21853135

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Project description:BackgroundThe prognosis of oral squamous cell carcinoma (OSCC) patients is difficult to predict or describe due to its high-level heterogeneity and complex aetiologic factors. Ferroptosis is a novel form of iron-dependent cell death that is closely related to tumour growth and progression. This study aims to clarify the predictive value of ferroptosis-related genes (FRGs) on the overall survival(OS) of OSCC patients.MethodsThe mRNA expression profile of FRGs and clinical information of patients with OSCC were collected from the TCGA database. Candidate differentially expressed ferroptosis-related genes (DE-FRGs) were identified by analysing differences between OSCC and adjacent normal tissues. A gene signature of prognosis-related DE-FRGs was established by univariate Cox analysis and LASSO analysis in the training set. Patients were then divided into high- and low-risk groups according to the cut-off value of risk scores, A nomogram was constructed to quantify the contributions of gene signature and clinical parameters to OS. Then several bioinformatics analyses were used to verify the reliability and accuracy of the model in the validation set. Finally, single-sample gene set enrichment analysis (ssGSEA) was also performed to reveal the underlying differences in immune status between different risk groups.ResultsA prognostic model was constructed based on 10 ferroptosis-related genes. Patients in high-risk group had a significantly worse OS (p < 0.001). The gene signature was verified as an independent predictor for the OS of OSCC patients (HR > 1, p < 0.001). The receiver operating characteristic curve displayed the favour predictive performance of the risk model. The prediction nomogram successfully quantified each indicator's contribution to survival and the concordance index and calibration plots showed its superior predictive capacity. Finally, ssGSEA preliminarily indicated that the poor prognosis in the high-risk group might result from the dysregulation of immune status.ConclusionThis study established a 10-ferroptosis-releated gene signature and nomogram that can be used to predict the prognosis of OSCC patients, which provides new insight for future anticancer therapies based on potential FRG targets.

Project description:The aim of the present study was to identify microRNAs (miRNAs) that predict the prognosis of patients with nasopharyngeal carcinoma by integrated bioinformatics analysis. First, the original microarray dataset GSE32960, including 312 nasopharyngeal carcinomas and 18 normal samples, was downloaded from the Gene Expression Omnibus database. In addition, 46 differentially expressed miRNAs (DEMs) were screened. Then, four miRNAs, including hsa‑miR‑142‑3p, hsa‑miR‑150, hsa‑miR‑29b, and hsa‑miR‑29c, were obtained as prognostic markers by combining univariate Cox regression analysis with weighted gene coexpression network analysis (WGCNA). Subsequently, the risk score of 312 NPC patients from the signature of miRNAs was calculated, and patients were divided into high‑risk or low‑risk groups. Notably, compared with patients with low‑risk scores, high‑risk groups had shorter disease‑free survival (DFS), overall survival (OS), and distant metastasis‑free survival (DMFS). Receiver operating characteristic curve (ROC) analysis indicated that the risk score was a very effective prognostic factor. Moreover, the Search Tool for the Database for Annotation, Visualization, and Integrated Discovery (DAVID), Cytoscape, starBase, and Retrieval of Interacting Genes database (STRING) were used to establish the miRNA‑mRNA correlation network and the protein‑protein interaction (PPI) network. In addition, the shared genes superimposing 888 protein‑coding genes targeted by four hub miRNAs and 1,601 upregulated differentially expressed mRNAs accounted for 127 and were used for subsequent gene functional enrichment analysis. In particular, biological pathway analysis indicated that these genes mainly participate in some vital pathways related to cancer pathogenesis, such as the focal adhesion, PI3K/Akt, p53, and mTOR signalling pathways. In summary, the identification of NPC patients with a four‑miRNA signature may increase the prognostic value and provide reference information for precision medicine.

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A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma.

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A novel molecular signature identified by systems genetics approach predicts prognosis in oral squamous cell carcinoma.

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