4.6 Article

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer

期刊

CANCERS
卷 14, 期 3, 页码 -

出版社

MDPI
DOI: 10.3390/cancers14030492

关键词

HNSCC; CDK7; pMED1; biomarker; TMA; prognosis; overall-survival

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资金

  1. Deutsche Krebshilfe [70113940]
  2. clinical scientist fellowship of medical faculty of the University of Luebeck [J26-2018]
  3. Deutsche Forschungsgemeinschaft [PE1179/15-1]

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This study investigated the clinical implications of CDK7 and pMED1 as potential biomarkers in head and neck squamous-cell cancer (HNSCC). The results showed that high levels of CDK7 were associated with lower survival rates and disease-free survival rates in HNSCC patients. Additionally, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In vitro studies also demonstrated the potential of CDK7 inhibition as a therapeutic target.
Simple Summary Head and neck squamous-cell cancer (HNSCC) is one of the most common cancer entities worldwide. Still, prognosis is rather poor, and therapeutic regimes come with harsh side-effects. In cancer research, certain biomolecules serve an important role as biomarkers that help to gain deeper insights into tumor biology. In this study, we sought to investigate the clinical implications of CDK7 and pMED1 as potential biomarkers in HNSCC patients. Therefore, we measured the levels of the above-mentioned proteins within tissue sections of our cohort using suitable software. Possible correlations of protein abundancy and clinicopathological features might help to guide future therapeutic decisions. We found that high levels of CDK7 in patients' tumor tissue point to lower survival and disease-free survival rates. There are current studies that investigate CDK7 as a therapeutic target in drug therapy. Our study provides a rationale that such therapies might benefit HNSCC patients. HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, CDK7 and MED1 have been ascribed prognostic implications by various studies. However, their prognostic value in head and neck squamous-cell cancer (HNSCC) remains elusive. We applied immunohistochemical staining of CDK7 and pMED1 on our large and clinically well-characterized HNSCC tissue cohort comprising 419 patients. Software-aided quantification of staining intensity was performed as a measure of protein expression. The following results were linked to the clinicopathological features of our cohort and correlated in different tissue types (primary tumor, lymph node metastasis, distant metastasis, recurrence). Upregulation CDK7 was associated with worse 5-year overall survival as well as disease-free survival in HNSCC while being independent of other known prognostic factors such as p16-status. Also, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In HNSCC CDK7 might serve as a novel prognostic marker to indicate the prognosis of patients. Furthermore, in vitro studies proved the feasibility of CDK7 inhibition with attenuating effects on cell proliferation underlining its remarkable translational potential for future therapeutic regimes.

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