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

Abstract

BackgroundCurrent 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 MethodsData 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).FindingsUsing 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). InterpretationWe 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.

Comparison of Immunohistochemistry Expression of CK7, HMWK and PSA in High-Grade Prostatic Adenocarcinoma and Bladder Transitional Cell Carcinoma

“…PSA had positive results in 97.4% of prostate tumors. However, a remarkable point in these studies was that HMWK was positive in 91.4% of bladder tumors, which was much higher than in other studies, including our studies (55.6%) (31).…”

Extracellular Matrix–receptor Interaction Signaling Genes Associated with Inferior Breast Cancer Survival

“…Furthermore, six-gene expression signatures can be used as independent prognostic markers in survival prediction of patients with breast cancer (11). Using TCGA database, Ong et al successfully identified a powerful biomarker panel for predicting the prognosis progression of patients with head and neck cancer (12). Therefore, by analyzing these big data, researchers can perform prospective clinical trials and evaluate the impact of candidate genes on breast cancer (13).…”

High expression of MLANA in the plasma of patients with head and neck squamous cell carcinoma as a predictor of tumor progression

“…Several groups have demonstrated different approaches to the identification and validation of prognostic factors in HNSCC, largely based on analyses of the primary tumor tissue itself. These include using single gene expression such as mRNA‐based signatures, miRNA expression, single protein biomarkers, or complex multiprotein signatures . Few studies have focused on plasma‐based biomarkers as prognostic factors in HNSCC.…”

“…These include using single gene expression such as mRNA-based signatures, miRNA expression, single protein biomarkers, or complex multiprotein signatures. [21][22][23][24][25] Few studies have focused on plasma-based biomarkers as prognostic factors in HNSCC. Le et al 26 found that serum Osteopontin levels correlated with tumor hypoxia, suggesting that this protein could be used to identify patients at high risk for tumor recurrence.…”