Abstract
Oral squamous cell carcinoma (OSCC) comprises a subset of head and neck squamous cell carcinoma (HNSCC) with poor therapeutic outcomes and high glycolytic dependency. Neoadjuvant chemotherapy regimens of docetaxel, cisplatin and 5-fluorouracil (TPF) are currently accepted as standard regimens for HNSCC patients with a high risk of distant metastatic spread. However, the antitumor outcomes of TPF neoadjuvant chemotherapy in HNSCC remain controversial. This study investigated the role of lactate dehydrogenase B (LDHB), a key glycolytic enzyme catalyzing the inter-conversion between pyruvate and lactate, in determining chemotherapy response and prognosis in OSCC patients. We discovered that a high protein level of LDHB in OSCC patients was associated with a poor response to TPF regimen chemotherapy as well as poor overall survival and disease-free survival. Our in-depth study revealed that high LDHB expression conferred resistance to taxol but not 5-fluorouracil or cisplatin. LDHB deletion sensitized OSCC cell lines to taxol, whereas the introduction of LDHB decreased sensitivity to taxol treatment. Taxol induced a pronounced impact on LDHB-down-regulated OSCC cells in terms of apoptosis, G2/M phase cell cycle arrest and energy metabolism. In conclusion, our study highlighted the critical role of LDHB in OSCC and proposed that LDHB could be used as a biomarker for the stratification of patients for TPF neoadjuvant chemotherapy and the determination of prognosis in OSCC patients.
Highlights
Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC) that has a poor therapeutic outcome and a 5-year survival rate of 50%–60% [1, 2]
We compared the expression of lactate dehydrogenase B (LDHB) with pathological parameters (Table 1) and found that LDHB expression was correlated with tumor recurrence (P = 0.011) and closely correlated with tumor size (P = 0.090), distant metastasis (P = 0.055) and TNM classification (P = 0.079) but was not significantly correlated with sex, age, histological grade or lymphatic metastasis
As LDHB is closely associated with a poor prognosis, to further examine its medical application, we analyzed the correlation between LDHB and the response to TPF neoadjuvant chemotherapy in a new set of OSCC patients
Summary
Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC) that has a poor therapeutic outcome and a 5-year survival rate of 50%–60% [1, 2]. Despite advances in multidisciplinary treatment modalities, no improvement in the 5-year survival rate has been achieved over the past 20 years [3]. Neoadjuvant chemotherapy has emerged as an effective way to reduce locally advanced or aggressive cancers to improve. LDHB Is Associated with Neoadjuvant Chemotherapy in OSCC
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