title: Lactate dehydrogenase B is associated with the response to neoadjuvant chemotherapy in oral squamous cell carcinoma.
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.
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Huaiqi
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
authors.forename: Heming
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D000077143:Docetaxel; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D020360:Neoadjuvant Therapy / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D007527:Isoenzymes; D043823:Taxoids; D000077143:Docetaxel; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1; D002945:Cisplatin; D005472:Fluorouracil