Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer
Menée sur des lignées cellulaires et des données portant sur des patientes atteintes de divers types de cancer du sein, cette étude évalue l'association entre la mesure de l'expression du gène de la lactate déshydrogénase B et la réponse à une chimiothérapie néoadjuvante
Purpose: Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer.
Methods: mRNA microarray data from breast cancer cell lines were used to identify bimodal genes - those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes.
Results: LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups (odds ratio = 21 for hormone-receptor (HR)-positive/HER2-negative; odds ratio = 10 for triple-negative). Furthermore, high LDHB predicted pathological complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (odds ratio = 4.1, P < .001) and triple-negative (odds ratio = 3.0, P = .003) cancers. For triple-negative tumors without pCR, high LDHB post-treatment also identified proliferative tumors with increased risk of recurrence (hazard ratio = 2.2, P = .006).
Conclusions: Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50-subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for breast cancer patients receiving neoadjuvant chemotherapy.
Clinical Cancer Research , résumé, 2013