Oncoproteomic and gene expression analyses identify prognostic biomarkers for second primary malignancy in patients with head and neck squamous cell carcinoma

Abstract

Patients with head and neck squamous cell carcinoma are at increased risk of developing a second primary malignancy, which is associated with poor prognosis and early death. To help improve clinical outcome, we aimed to identify biomarkers for second primary malignancy risk prediction using the routinely obtained formalin-fixed paraffin-embedded tissues of the index head and neck cancer. Liquid chromatography-tandem mass spectrometry was initially performed for candidate biomarker discovery in 16 pairs of primary cancer tissues and their matched normal mucosal epithelia from head and neck squamous cell carcinoma patients with or without second primary malignancy. The 32 candidate proteins differentially expressed between head and neck cancers with and without second primary malignancy were identified. Among these, 30 selected candidates and seven more from literature review were further studied using NanoString nCounter gene expression assay in an independent cohort of 49 head and neck cancer patients. Focusing on the p16-negative cases, we showed that a multivariate logistic regression model comprising the expression levels of ITPR3, KMT2D, EMILIN1, and the patient's age can accurately predict second primary malignancy occurrence with 88% sensitivity and 75% specificity. Furthermore, using Cox proportional hazards regression analysis and survival analysis, high expression levels of ITPR3 and DSG3 were found to be significantly associated with shorter time to second primary malignancy development (log-rank test P = 0.017). In summary, we identified a set of genes whose expressions may serve as the prognostic biomarkers for second primary malignancy occurrence in head and neck squamous cell carcinomas. In combination with the histopathologic examination of index tumor, these biomarkers can be used to guide the optimum frequency of second primary malignancy surveillance, which may lead to early diagnosis and better survival outcome.

Radiotherapy-Induced Changes in the Systemic Immune and Inflammation Parameters of Head and Neck Cancer Patients

“…The 5 years survival rate is under 65% due mostly to the late diagnosis in the absence of early symptoms [3]. About 90% of all head and neck cancers are squamous cell carcinomas (HNSCC) [4]. Apart of surgery the main treatment protocol for HNSCC is radiotherapy (RT) combined with chemotherapy [5].…”

Thymoma appearing 9�years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review

“…The mechanism (in terms of genomics and proteomics) of SPTs in patients with H&N cancer is crucial and has been well analyzed and reported. For example, Bunbanjerdsuk et al have analyzed the oncoproteomics and gene expression and reported ITPR3, KMT2D , and EMILIN1 as prognostic factors in SPT for patients with H&N cancer (80). da Silva et al have reported that epithelial-mesenchymal transition markers such as E-cadherin and beta-catenin , exhibit a significant prognostic impact in multiple primary oral SCC cases (81).…”

Identification and Clinical Validation of Genes Signatures With Grade and Survival in Head and Neck Carcinomas

“…Among them that have been functionally characterized, several has been linked to malignant progression [13][14] . Notably, many genes have key roles for diagnostic accuracy and predicting the prognosis [15][16] .…”