Dataset Information

Validation of a Machine Learning Model to Predict Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Head and neck squamous-cell carcinoma (HNSCC) is a disease with a generally poor prognosis; half of treated patients eventually develop recurrent and/or metastatic (R/M) disease. Patients with R/M HNSCC generally have incurable disease with a median survival of 10 to 15 months. Although immune-checkpoint blockade (ICB) has improved outcomes in patients with R/M HNSCC, identifying patients who are likely to benefit from ICB remains a challenge. Biomarkers in current clinical use include tumor mutational burden and immunohistochemistry for programmed death-ligand 1, both of which have only modest predictive power. Machine learning (ML) has the potential to aid in clinical decision-making as an approach to estimate a tumor's likelihood of response or a patient's likelihood of experiencing clinical benefit from therapies such as ICB. Previously, we described a random forest ML model that had value in predicting ICB response using 11 or 16 clinical, laboratory, and genomic features in a pan-cancer development cohort. However, its applicability to certain cancer types, such as HNSCC, has been unknown, due to a lack of cancer-type-specific validation. Here, we present the first validation of a random forest ML tool to predict the likelihood of ICB response in patients with R/M HNSCC. The tool had adequate predictive power for tumor response (area under the receiver operating characteristic curve = 0.65) and was able to stratify patients by overall (HR = 0.53 [95% CI 0.29-0.99], p = 0.045) and progression-free (HR = 0.49 [95% CI 0.27-0.87], p = 0.016) survival. The overall accuracy was 0.72. Our study validates an ML predictor in HNSCC, demonstrating promising performance in a novel cohort of patients. Further studies are needed to validate the generalizability of this algorithm in larger patient samples from additional multi-institutional contexts.

SUBMITTER: Lee AS

PROVIDER: S-EPMC10778506 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Validation of a Machine Learning Model to Predict Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

Lee Andrew Sangho AS Valero Cristina C Yoo Seong-Keun SK Vos Joris L JL Chowell Diego D Morris Luc G T LGT

Cancers 20231229 1

Head and neck squamous-cell carcinoma (HNSCC) is a disease with a generally poor prognosis; half of treated patients eventually develop recurrent and/or metastatic (R/M) disease. Patients with R/M HNSCC generally have incurable disease with a median survival of 10 to 15 months. Although immune-checkpoint blockade (ICB) has improved outcomes in patients with R/M HNSCC, identifying patients who are likely to benefit from ICB remains a challenge. Biomarkers in current clinical use include tumor mut ...[more]

PMID: 38201602

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Project description:Background and purposeHead and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)-based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients.Materials and methodsThe expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3).ResultsBy using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients' overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02-1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response.ConclusionCollectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.

Project description:IntroductionHead and neck squamous cell carcinoma (HNSCC), a highly heterogeneous malignancy is often associated with unfavorable prognosis. Due to its unique anatomical position and the absence of effective early inspection methods, surgical intervention alone is frequently inadequate for achieving complete remission. Therefore, the identification of reliable biomarker is crucial to enhance the accuracy of screening and treatment strategies for HNSCC.MethodTo develop and identify a machine learning-derived prognostic model (MLDPM) for HNSCC, ten machine learning algorithms, namely CoxBoost, elastic network (Enet), generalized boosted regression modeling (GBM), Lasso, Ridge, partial least squares regression for Cox (plsRcox), random survival forest (RSF), stepwise Cox, supervised principal components (SuperPC), and survival support vector machine (survival-SVM), along with 81 algorithm combinations were utilized. Time-dependent receiver operating characteristics (ROC) curves and Kaplan-Meier analysis can effectively assess the model's predictive performance. Validation was performed through a nomogram, calibration curves, univariate and multivariate Cox analysis. Further analyses included immunological profiling and gene set enrichment analyses (GSEA). Additionally, the prediction of 50% inhibitory concentration (IC50) of potential drugs between groups was determined.ResultsFrom analyses in the HNSCC tissues and normal tissues, we found 536 differentially expressed genes (DEGs). Subsequent univariate-cox regression analysis narrowed this list to 18 genes. A robust risk model, outperforming other clinical signatures, was then constructed using machine learning techniques. The MLDPM indicated that high-risk scores showed a greater propensity for immune escape and reduced survival rates. Dasatinib and 7 medicine showed the superior sensitivity to the high-risk NHSCC, which had potential to the clinical.ConclusionsThe construction of MLDPM effectively eliminated artificial bias by utilizing 101 algorithm combinations. This model demonstrated high accuracy in predicting HNSCC outcomes and has the potential to identify novel therapeutic targets for HNSCC patients, thus offering significant advancements in personalized treatment strategies.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients.MethodsWe downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and p value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration.ResultsCox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells.ConclusionLINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.

Dataset Information

Validation of a Machine Learning Model to Predict Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

Publications

Validation of a Machine Learning Model to Predict Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.

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