The MIMIC Study: Prognostic Role and Cutoff Definition of Monocyte-to-Lymphocyte Ratio and Lactate Dehydrogenase Levels in Metastatic Colorectal Cancer

Abstract

Background. Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). Material and Methods. This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. Results. At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I. , 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. Conclusion. MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC.

Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti–PD-1 Therapy

“…Currently, the mechanisms underlying the efficacy of anti–PD-1 treatment by inflammatory indicators are not very explicit. On the one side, MLR values in peripheral circulating blood were significantly associated with prognosis in both metastatic GC and CRC ( Basile et al, 2020 ; Zhou et al, 2020 ). On the other side, myeloid-derived suppressor cells (MDSCs) are a hallmark of tumor-associated inflammation that mediate the suppression of T cell responses in lymphomas ( Raber et al, 2014 ).…”

Abilities of Pre-Treatment Inflammation Ratios as Classification or Prediction Models for Patients with Colorectal Cancer

“…Özgehan et al reported that NLR showed significantly high values in patients with positive lymph nodes [ 39 ]. LMR has been proposed as a prognostic factor for metastasis in colorectal cancer but did not prove such clinical reliability as NLR or dNLR [ 40 ]. Lu et al [ 41 ] stated that TNM in association with PLR has better prognostic capacity than the TNM classification alone and that PLR can be used as an additional parameter to TNM staging.…”

The Prognostic Value of Preoperative Serum Lactate Dehydrogenase (LDH) Levels in Patients Underwent Curative-intent Hepatectomy For Colorectal Liver Metastases: A Two-Center Cohort Study

“…Targeting CRLM metabolism provides a promising therapeutic approach to restore local NK-cell activity [33]. In TME, lactate may also inhibit the innate and adaptive immunity by promoting immune-suppressive proin ammatory cytokines such as TNF-α, IL-1, IL-6, prostaglandins, nuclear factor-κB, recruiting tumor-associated macrophages (TAMs) and promoting their conversion into immunosuppressive (M2) phenotype [34,35]. LDH therefore impacts the complex interplay between TME and host immune system, modulates tumor initiation, proliferation, invasion and migration potential [36].…”