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DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.

ABSTRACT: Gemcitabine is a potential chemotherapy drug for treatment of head and neck squamous cell carcinoma (HNSCC), however, the poor or partial response of HNSCC patients to gemcitabine demonstrated the urgent need for gemcitabine biomarkers to improve the therapy. In present work, 10 HNSCC cell lines were employed to figure out the biomarkers for gemcitabine sensitivity. The sensitivities of these 10 cell lines to gemcitabine and the basal expression of these cell lines was investigated, the correlation between gemcitabine response (IC50 dose) and gene expression was investigated by Pearson correlation and FDR estimation. The top seven positive genes responsible for gemcitabine sensitivity were validated by qPCR in these 10 HNSCC cell lines, while only two genes (SBF1 and ZNF195) were expression-correlated to gemcitabine response. Furthermore, ZNF195 expression was closely associated with gemcitabine sensitivity in the subsequent independent validation in cell lines from various types of cancer. Our work might provide potential biomarkers for gemcitabine sensitivity in HNSCC and various type of cancer.

SUBMITTER: Zhu MH

PROVIDER: S-EPMC4014231 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.

Zhu Min-Hui MH Ji Shun-Long SL Zhang Cai-Yun CY Cui Long L Xiong Lei L Zheng Hong-Liang HL

International journal of clinical and experimental pathology 20140315 4

Gemcitabine is a potential chemotherapy drug for treatment of head and neck squamous cell carcinoma (HNSCC), however, the poor or partial response of HNSCC patients to gemcitabine demonstrated the urgent need for gemcitabine biomarkers to improve the therapy. In present work, 10 HNSCC cell lines were employed to figure out the biomarkers for gemcitabine sensitivity. The sensitivities of these 10 cell lines to gemcitabine and the basal expression of these cell lines was investigated, the correlat ...[more]

PMID: 24817947

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Project description:Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Dataset Information

DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.

Publications

DNA microarray reveals ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines.

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