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Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

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  • Ram Bhupal Reddy
  • Samanta S Khora
  • Amritha Suresh

Abstract

Head and neck squamous cell carcinomas (HNSCC) includes multiple subsites that exhibit differential treatment outcome, which is in turn reflective of tumor stage/histopathology and molecular profile. This study hypothesized that the molecular profile is an accurate prognostic adjunct in patients triaged based on clinico-pathological characteristics. Towards this effect, publically available micro-array datasets (n = 8), were downloaded, classified based on HPV association (n = 83) and site (tongue n = 88; laryngopharynx n = 53; oropharynx n = 51) and re-analyzed (Genespring; v13.1). The significant genes were validated in respective cohorts in The Cancer Genome Atlas (TCGA) for correlation with clinico-pathological parameters/survival. The gene entities (n = 3258) identified from HPV based analysis, when validated in TCGA identified the subset specifically altered in HPV+ HNSCC (n = 63), with three genes showing survival impact (RPP25, NUDCD2, NOVA1). Site-specific meta-analysis identified respective differentials (tongue: 3508, laryngopharynx: 4893, oropharynx: 2386); validation in TCGA revealed markers with high incidence (altered in >10% of patients) in tongue (n = 331), laryngopharynx (n = 701) and oropharynx (n = 404). Assessment of these genes in clinical sub-cohorts of TCGA indicated that early stage tongue (MTFR1, C8ORF33, OTUD6B) and laryngeal cancers (TWISTNB, KLHL13 and UBE2Q1) were defined by distinct prognosticators. Similarly, correlation with perineural/angiolymophatic invasion, identified discrete marker panels with survival impact (tongue: NUDCD1, PRKC1; laryngopharynx: SLC4A1AP, PIK3CA, AP2M1). Alterations in ANO1, NUDCD1, PIK3CA defined survival in tongue cancer patients with nodal metastasis (node+ECS-), while EPS8 is a significant differential in node+ECS- laryngopharyngeal cancers. In oropharynx, wherein HPV is a major etiological factor, distinct prognosticators were identified in HPV+ (ECHDC2, HERC5, GGT6) and HPV- (GRB10, EMILIN1, FNDC1). Meta-analysis in combination with TCGA validation carried out in this study emphasized on the molecular heterogeneity inherent within HNSCC; the feasibility of leveraging this information for improving prognostic efficacy is also established. Subject to large scale clinical validation, the marker panel identified in this study can prove to be valuable prognostic adjuncts.

Suggested Citation

  • Ram Bhupal Reddy & Samanta S Khora & Amritha Suresh, 2019. "Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-29, July.
    • Handle: RePEc:plo:pone00:0218989
    DOI: 10.1371/journal.pone.0218989
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    References listed on IDEAS

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    1. Indre Piragyte & Thomas Clapes & Aikaterini Polyzou & Ramon I. Klein Geltink & Stylianos Lefkopoulos & Na Yin & Pierre Cauchy & Jonathan D. Curtis & Lhéanna Klaeylé & Xavier Langa & Cora C. A. Beckman, 2018. "A metabolic interplay coordinated by HLX regulates myeloid differentiation and AML through partly overlapping pathways," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    2. Ram Bhupal Reddy & Anupama Rajan Bhat & Bonney Lee James & Sindhu Valiyaveedan Govindan & Rohit Mathew & Ravindra DR & Naveen Hedne & Jeyaram Illiayaraja & Vikram Kekatpure & Samanta S Khora & Wesley , 2016. "Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-21, January.
    3. Shuo Qie & Mrinmoyee Majumder & Katarzyna Mackiewicz & Breege V. Howley & Yuri K. Peterson & Philip H. Howe & Viswanathan Palanisamy & J. Alan Diehl, 2017. "Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
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