A three gene immunohistochemical panel serves as an adjunct to clinical staging of patients with head and neck cancer

Autor: Tony Kiat Hon Lim, Chin-Ann Johnny Ong, Fui Teen Chong, Nicholas B. Shannon, Xuan Qiu, Daniel Shao-Weng Tan, Ke Li, Stefan Mueller, Gerald Tay, Jacqueline S.G. Hwang, Khee Chee Soo, Hiang Khoon Tan, Mei Kim Ang, Sze Min Lek, N. Gopalakrishna Iyer, Thakshayeni Skanthakumar, Kelvin K.N. Koh, Ngian-Chye Tan
Rok vydání: 2017
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Chin-Ann J. Ong 1, 3, * , Nicholas B. Shannon 2, * , Stefan Mueller 3, 7, * , Sze Min Lek 2, * , Xuan Qiu 1 , Fui Teen Chong 4 , Ke Li 2 , Kelvin K.N. Koh 2 , Gerald C.A. Tay 1, 7 , Thakshayeni Skanthakumar 3 , Jacqueline S.G. Hwang 5 , Tony Kiat Hon Lim 5 , Mei Kim Ang 6 , Daniel S.W. Tan 6 , Ngian-Chye Tan 7 , Hiang Khoon Tan 7 , Khee Chee Soo 7 and N. Gopalakrishna Iyer 2, 4, 7 1 Department of General Surgery, Singapore General Hospital, S169856, Singapore 2 Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, S169857, Singapore 3 Division of Surgical Oncology, National Cancer Centre, S169610, Singapore 4 Cancer Therapeutics Research Laboratory, National Cancer Centre, S169610, Singapore 5 Department of Anatomical Pathology, Singapore General Hospital, S169856, Singapore 6 Department of Medical Oncology, National Cancer Centre, S169610, Singapore 7 Singhealth Duke-NUS Head and Neck Centre, Singhealth, S169856, Singapore * These authors contributed equally to this work Correspondence to: N. Gopalakrishna Iyer, email: gopaliyer@nccs.com.sg Keywords: head and neck squamous cell carcinoma, immunohistochemistry, genomics Received: February 21, 2017 Accepted: June 08, 2017 Published: June 19, 2017 ABSTRACT Background: Current management of head and neck squamous cell carcinoma (HNSCC) depends on tumor staging. Despite refinements in clinical staging algorithms, outcomes remain unchanged for the last two decades. In this study, we set out to identify a small, clinically applicable molecular panel to aid prognostication of patients with HNSCC. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) was used to derive copy number aberrations and expression changes to identify putative prognostic genes. To account for cross entity relevance of the biomarkers, HNSCC ( n = 276), breast ( n = 808) and lung cancer ( n = 282) datasets were used to identify robust and reproducible markers with prognostic potential. Validation was performed using immunohistochemistry (IHC) on tissue microarrays of an independent cohort of HNSCC ( n = 333). Findings: Using GISTIC algorithm together with gene expression analysis, we identified six putative prognostic genes in at least two out of three cancers analyzed, of which four were successfully optimized for automated IHC. Of these, three were successfully validated; each molecular target being significantly prognostic on univariate analysis. Patients were differentially segregated into four prognostic groups based on the number of genes dysregulated ( p < 0.001). The IHC panel remained an independent predictor of survival after adjusting for known survival covariates including clinical staging criteria in a multivariate Cox regression model ( p < 0.001). Interpretation: We have identified and validated a clinically applicable IHC biomarker panel that is independently associated with overall survival. This panel is readily applicable, serving as a useful adjunct to current staging systems and provides novel targets for future therapeutic strategies.
Databáze: OpenAIRE
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