Machine learning-based identification of a consensus immune-derived gene signature to improve head and neck squamous cell carcinoma therapy and outcome

Abstract

BackgroundHead and neck squamous cell carcinoma (HNSCC), an extremely aggressive tumor, is often associated with poor outcomes. The standard anatomy-based tumor–node–metastasis staging system does not satisfy the requirements for screening treatment-sensitive patients. Thus, an ideal biomarker leading to precise screening and treatment of HNSCC is urgently needed.MethodsTen machine learning algorithms—Lasso, Ridge, stepwise Cox, CoxBoost, elastic network (Enet), partial least squares regression for Cox (plsRcox), random survival forest (RSF), generalized boosted regression modelling (GBM), supervised principal components (SuperPC), and survival support vector machine (survival-SVM)—as well as 85 algorithm combinations were applied to construct and identify a consensus immune-derived gene signature (CIDGS).ResultsBased on the expression profiles of three cohorts comprising 719 patients with HNSCC, we identified 236 consensus prognostic genes, which were then filtered into a CIDGS, using the 10 machine learning algorithms and 85 algorithm combinations. The results of a study involving a training cohort, two testing cohorts, and a meta-cohort consistently demonstrated that CIDGS was capable of accurately predicting prognoses for HNSCC. Incorporation of several core clinical features and 51 previously reported signatures, enhanced the predictive capacity of the CIDGS to a level which was markedly superior to that of other signatures. Notably, patients with low CIDGS displayed fewer genomic alterations and higher immune cell infiltrate levels, as well as increased sensitivity to immunotherapy and other therapeutic agents, in addition to receiving better prognoses. The survival times of HNSCC patients with high CIDGS, in particular, were shorter. Moreover, CIDGS enabled accurate stratification of the response to immunotherapy and prognoses for bladder cancer. Niclosamide and ruxolitinib showed potential as therapeutic agents in HNSCC patients with high CIDGS.ConclusionCIDGS may be used for stratifying risks as well as for predicting the outcome of patients with HNSCC in a clinical setting.