Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma

Abstract

BackgroundThe immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients.MethodsHigh-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers.ResultsCollectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes (PVR, TNFRSF12A, IL21R, and SOCS1) were significantly associated with overall survival (OS). Integrating these genes with Path_N stage, a multiplex model was built and suggested better performance in determining 5 years OS (receiver operating characteristic (ROC) analysis, area under the curve (AUC)=0.709) than others. Further protein-based validation was conducted in 115 HNSCC patients. Similarly, high expression of PVR and TNFRSF12A were associated with poor OS (Kaplan-Meier p=0.017 and 0.0032), while high expression of IL21R and SOCS1 indicated favorable OS (Kaplan-Meier p<0.0001 and =0.0018). The integrated model with Path_N stage still demonstrated efficacy in OS evaluation (Kaplan-Meier p<0.0001, ROC AUC=0.893). Besides, the four prognostic genes were significantly correlated with activated CD8+ T cells, CD4+ T cells, follicular helper T cells and regulatory T cells, implying the possible involvement of these genes in the immunoregulation and development of HNSCC.ConclusionsThe well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.

Stromal Score-Based Gene Signature: A Prognostic Prediction Model for Colon Cancer

“…However, it is necessary to transfer the preclinical medical findings into clinical applications. A recent study utilizing the profiles of clinical samples and TCGA cases established a prognostic prediction model of high quality for head and neck squamous cell carcinoma by encompassing both immune-related gene signature and clinicopathological factor, providing a powerful tool for the prognostic prediction in clinical practice in addition to TNM staging ( Yao et al, 2020 ). Meanwhile, with the rapid development in techniques of next-generation sequencing, it may become more and more convenient and popularized to help evaluate prognostic outcomes and make treatment decisions for cancer patients based on transcriptomic profiles of target genes in their tumor tissues.…”

Immune infiltration and immune gene signature predict the response to fluoropyrimidine-based chemotherapy in colorectal cancer patients

“…17 Due to the excellent performance of CIBERSORT, its application in studying cell heterogeneity has aroused increasing attention. [18][19][20] For example, Xiong et al analyzed the clinical significant of TIICs in CRC by using CIBERSORT 16 and Narayanan et al performed CIBERSORT algorithm to identify TIICs associated with OS of microsatellite unstable CRC patients. 21 However, The impact of TIICs on the prognosis of patients treated with fluoropyrimidine is not yet conclusive.…”

Stromal Score-based Gene Signature: A Prognostic Prediction Model for Colon Cancer

“…However, it is necessary to transfer the preclinical medical ndings into clinical applications. A recent study utilizing the pro les of clinical samples and TCGA cases established a prognostic prediction model of high quality for head and neck squamous cell carcinoma by encompassing both immune-related gene signature and clinicopathological factor, providing a powerful tool for the prognostic prediction in clinical practice in addition to TNM staging [37]. Meanwhile, with the rapid development in techniques of next-generation sequencing, it may become more and more convenient and popularized to help evaluate prognostic outcomes and make treatment decisions for cancer patients based on transcriptomic pro les of target genes in their tumor tissues.…”