Elevated pretreatment lactate dehydrogenase and albumin-to-alkaline phosphatase ratio predict poor prognosis and early treatment discontinuation in head and neck cancer patients with preexistent diabetes mellitus

Increased serum lactate dehydrogenase (LDH) activity is considered as a marker of cellular necrosis and serves as a metabolomic diagnostic marker in several types of cancer including head and neck squamous cell carcinoma (HNSCC). LDH, an enzyme involved in the glycolytic cycle, is correlated not only with the activation of oncogenes such as HIF-α and Myc, but also with effects such as tumor proliferation and metastasis. Serum alkaline phosphatase (ALP) is a marker of cell differentiation and tumor induction. Albumin-to-alkaline phosphatase ratio (AAPR) could be an advantageous biomarker due to its easily accessible dynamics and cost-effectiveness. Elevated values of AAPR could be associated with longer overall survival (OS) in cases with solid tumors. Diabetes mellitus (DM) could influence the outcome of patients with HNSCC by contributing to insulin resistance and chronic inflammation, and by being involved in various aspects of carcinogenesis, disease progression and metastasis. However, the use of antihyperglycemic medications (metformin) can have beneficial effects by inhibiting tumor metabolic pathways. The biomarker role of LDH and AAPR in HNSCC patients with DM has been less evaluated. The purpose of the study was to assess the prognostic value of pretreatment serum lactate dehydrogenase (LDH) and albumin-to-alkaline phosphatase ratio (AAPR) in predicting the duration of non-surgical oncological treatment and glycemic control in cases of head and neck cancers patients with DM, including cases selected from the database of the oncology clinic and oncology outpatient clinic of the Craiova County Hospital. Both LDH and AAPR can be used as pre-treatment biomarkers predictive of treatment response, or prognostic tools included in complex multi-parametric models in HNC associated with DM. However, given the impact of short-term glycemic control on the LDH level, it is necessary to evaluate these biomarkers after assessing and controlling for DM, and with the recommended cut-off value set around 0.5. Due to the limited number of cases, it is necessary to validate the results in multicentric trials with a larger number of patients (Tab. 5, Ref. 50). Keywords: diabetes mellitus, HNC, LDH, AAPR, biomarkers, predictive, head and neck cancers, lactate dehydrogenase, albumin-to-alkaline phosphatase ratio.