Abstract 97P
Background
Serum lactate dehydrogenase (LDH) may be prognostic in metastatic colorectal cancer (mCRC). Yet data of related clinical-molecular traits is sparse, calling for subgroup specification.
Methods
Clinical data of patients with newly diagnosed de novo mCRC between 2019-2023 in our center was analyzed. Age, gender, comorbidities, smoking, family history, primary tumor site, metastatic sites (liver (LM), peritoneal, lung, bone), number of LM, MSI, RAS-RAF mutation status, CEA-Ca19-9, neutrophile/lymphocyte ratio, serum albumin, uric acid, LDH levels, treatment, response, and survival data were analyzed. The Cancer Genome Atlas Program (TCGA) data was utilized for LDHA gene expression (relative to normal samples, z score >2 defined as high expression).
Results
136 patients were included. Median serum LDH level was 231 U/L (range 106-5655). 55.1% (n=75) had LDH above upper normal limit. Of those, 16% (n=12) had LDH >1000 U/L. Among the clinical parameters, only presence of LM (p=0.01), number of LM (≥5 vs <5, p=0.00) were significantly associated and, CEA (p=0.00), CRP (p=0.02) levels were significantly positively correlated with high LDH levels. Among patients with only-LM; responders to 5-FU-platinum doublet had lower serum LDH level (p=0.02); higher LDH levels were associated with worse PFS (HR: 1.004, 95% CI: 1.001-1.007, p=0.00) and OS ((HR: 1.007, 95% CI: 1.003-1.011, p=0.00). Among 84 patients of TCGA cohort with mCRC, 16.7% (n=14) had high LDHA expression. High expression was associated with lower MSI MANTIS score (p=0.04) and higher hypoxia scores (p for Buffa:0.00, Winter: 0.00). Tumor mutational burden and aneuploidy score were not associated with LDHA expression. Among 10 genes with highest genomic alteration frequency (APC, TP53, KRAS, COL22A1, TTN, ADGRB1, MYBL1, FNTA, HGSNAT, TNFRSF11B), only COL22A1 (p=0.01), ADGRB1(p=0.04) and MYBL1 (p=0.04) were associated with the high LDHA expression. Expression of epithelial-metabolic pathway genes was correlated with high LDHA expression, suggesting its link with consensus molecular subtype 3.
Conclusions
This study proposes serum LDH as a potential biomarker in microsatellite stable, liver metastatic CRC, with its expression linked to specific molecular traits.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.