Dataset Information

Bioinformatic Analysis Reveals an Immune/Inflammatory-Related Risk Signature for Oral Cavity Squamous Cell Carcinoma.

ABSTRACT: High-throughput gene expression profiling has recently emerged as a promising technique that provides insight into cancer subtype classification and improved prediction of prognoses. Immune/inflammatory-related mRNAs may potentially enrich genes to allow researchers to better illustrate cancer microenvironments. Oral cavity squamous cell carcinoma (OC-SCC) exhibits high morbidity and poor prognosis compared to that of other types of head and neck squamous cell carcinoma (HNSCC), and these differences may be partially due to differences within the tumor microenvironments. Based on this, we designed an immune-related signature to improve the prognostic prediction of OC-SCC. A cohort of 314 OC-SCC samples possessing whole genome expression data that were sourced from The Cancer Genome Atlas (TCGA) database was included for discovery. The GSE41613 database was used for validation. A risk score was established using immune/inflammatory signatures acquired from the training dataset. Principal components analysis, GO analysis, and gene set enrichment analysis were used to explore the bioinformatic implications. When grouped by the dichotomized risk score based on the signature, this classifier could successfully discriminate patients with distinct prognoses within the training and validation cohorts (P < 0.05 in both cohorts) and within different clinicopathological subgroups. Similar somatic mutation patterns were observed between high and low risk score groups, and different copy number variation patterns were also identified. Further bioinformatic analyses suggested that the lower risk score group was significantly correlated with immune/inflammatory-related biological processes, while the higher risk score group was highly associated with cell cycle-related processes. The analysis indicated that the risk score was a robust predictor of patient survival, and its functional annotation was well established. Therefore, this bioinformatic-based immune-related signature suggested that the microenvironment of OC-SCC could distinguish among patients with different underlying biological processes and clinical outcomes, and the use of this signature may shed light on future OC-SCC classification and therapeutic design.

SUBMITTER: Bai S

PROVIDER: S-EPMC6930791 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bioinformatic Analysis Reveals an Immune/Inflammatory-Related Risk Signature for Oral Cavity Squamous Cell Carcinoma.

Bai Shuang S Yan Ying-Bin YB Chen Wei W Zhang Ping P Zhang Tong-Mei TM Tian Yuan-Yuan YY Liu Hao H

Journal of oncology 20191213

High-throughput gene expression profiling has recently emerged as a promising technique that provides insight into cancer subtype classification and improved prediction of prognoses. Immune/inflammatory-related mRNAs may potentially enrich genes to allow researchers to better illustrate cancer microenvironments. Oral cavity squamous cell carcinoma (OC-SCC) exhibits high morbidity and poor prognosis compared to that of other types of head and neck squamous cell carcinoma (HNSCC), and these differ ...[more]

PMID: 31911802

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Project description:ImportancePostradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation.ObjectiveTo determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC.Design, setting, and participantsThis retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022.ExposureHead and neck irradiation involving the oral cavity before the diagnosis of OCSCC.Main outcomes and measuresThe primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed.ResultsA total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-β compared with sporadic OCSCC.Conclusions and relevanceThis retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Project description:Objectives: This study was designed to identify a messenger RNA (mRNA) expression signature to predict survival in patients with oral squamous cell carcinoma (OSCC). Methods: mRNA expression profiles were integrated with clinical data from 280 samples, including 19 normal tissues and 261 OSCC tissues in The Cancer Genome Atlas. We identified differentially expressed mRNAs (DEmRNAs) between the OSCC and normal tissue samples and developed a novel mRNA-focused expression signature using a Cox regression analysis and other bioinformatic methods. The prognostic value of this signature was evaluated by Kaplan-Meier analysis, multivariable COX regression, and receiver operating characteristic (ROC) curve analysis. Protein-protein interaction (PPI) network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to predict the function of the DEmRNAs. Signature-related mRNAs were analyzed by gene set enrichment analyses (GSEA) and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in 20 paired OSCC and adjacent healthy tissues. Results: We identified a novel 5-mRNA expression signature (HOXA1, CELSR3, HIST1H3J, ZFP42, and ASCL4) that could predict patient outcomes in OSCC. The risk score based on the signature was able to separate OSCC patients into high- and low-risk groups that showed significantly different overall survival (p < 0.001, log-rank test). The signature was further validated as an effective independent prognostic predictor of OSCC by multivariate Cox regression analysis (hazard ratio = 3.747, confidence interval: 2.279-5.677, p < 0.001) and ROC curve of the third year (area under the curve = 0.733). Functional analysis demonstrated that the key hub genes in the PPI network were mainly enriched in cell division, cell proliferation, and the p53 signaling pathway. GSEA results showed that the 5 mRNAs were significantly enriched in mismatch repair, DNA replication, and the NOTCH signaling pathway. Finally, qRT-PCR results showed that the 5 mRNAs were upregulated in OSCC tissue in agreement with the predictions from our bioinformatics analysis. Conclusions: We identified a novel 5-mRNA signature that could predict the survival of patients with OSCC and may be a promising biomarker for personalized cancer treatments.

Project description:BackgroundCancer utilizes immunosuppressive mechanisms to create a tumor microenvironment favorable for its progression. The purpose of this study is to histologically characterize the immunological properties of the tumor microenvironment of oral squamous cell carcinoma (OSCC) and identify key molecules involved in the immunological microenvironment and patient prognosis.MethodsFirst, overlapping differentially expressed genes (DEGs) were screened from OSCC transcriptome data in public databases. Correlation analysis of DEGs with known immune-related genes identified genes involved in the immune microenvironment of OSCC. Next, stromal patterns of tumor were classified and immunohistochemical staining was performed for immune cell markers (CD3, CD4, Foxp3, CD8, CD20, CD68, and CD163), programmed death-ligand 1 (PD-L1), and guanylate binding protein 5 (GBP5) in resected specimens obtained from 110 patients with OSCC who underwent resection. Correlations between each factor and their prognostic impact were analyzed.ResultsAmong the novel OSCC-specific immune-related genes screened (including ADAMDEC1, CXCL9, CXCL13, DPT, GBP5, IDO1, and PLA2G7), GBP5 was selected as the target gene. Histopathologic analysis showed that multiple T-cell subsets and CD20-positive cells were less common in the advanced stages, whereas CD163-positive cells were more common in advanced stages. The immature type in the stromal pattern category was associated with less immune cell infiltration, lower expression of PD-L1 in immune cells, lower expression of GBP5 in the stroma, and shorter overall survival and recurrence-free survival. Expression of GBP5 in the tumor and stroma correlated with immune cell infiltration of tumors and PD-L1 expression in tumor and immune cells. Patients with low tumor GBP5 expression and high stromal expression had significantly longer overall survival and recurrence-free survival.ConclusionsThe stromal pattern category may reflect both invasive and immunomodulatory potentials of cancer-associated fibroblasts in OSCC. GBP5 has been suggested as a potential biomarker to predict the prognosis and therapeutic efficacy of immune checkpoint inhibitors.

Dataset Information

Bioinformatic Analysis Reveals an Immune/Inflammatory-Related Risk Signature for Oral Cavity Squamous Cell Carcinoma.

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Bioinformatic Analysis Reveals an Immune/Inflammatory-Related Risk Signature for Oral Cavity Squamous Cell Carcinoma.

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