Discussion
gallstones, tumor, cancers, death, CRC, fatty liver, ALRI, cirrhosis, human malignancies, hepatobiliary disorders, heart, skeletal muscle, mitochondrial dysfunction
GALLSTONES, TUMOR, CHOLECYSTITIS, CANCERS, RECURRENCE, FATTY LIVER, CIRRHOSIS, HEPATOBILIARY DISORDERS, MICROSATELLITE INSTABILITY, ACUTE VIRAL HEPATITIS, GALLBLADDER POLYPS, MITOCHONDRIAL DYSFUNCTION
Serum liver enzyme markers, as readily-available and non-invasive clinical parameters, have great potential for predicting the prognosis of human malignancies. Our study, for the first time, comprehensively evaluated the prognostic values of lactate dehydrogenase, alkaline phosphatase, De Ritis ratio, APRI, ALRI, ANRI, and APPRI in a large retrospective CRC cohort. Among these serum liver enzyme markers, only De Ritis ratio was identified as an independent prognostic factor for predicting the OS and DFS of patients with stage II/III CRC, which was also verified in the testing set. Based on the results of C-index, time-dependent ROC, and decision curve analyses, the nomograms combining De Ritis ratio and significant clinicopathological features had higher accuracy, improved discrimination, and greater clinical benefits in predicting the overall survival, recurrence/metastasis compared with TNM and AJCC staging.Aspartate aminotransferase and alanine aminotransferase are enzymes produced by cancerous and non-cancerous cells, and then released into peripheral blood. Alanine aminotransferase is mainly distributed in the liver, while aspartate aminotransferase is widely expressed in different tissues including the liver, heart, skeletal muscle, and kidney [The De Ritis ratio, initially described as a characteristic of acute viral hepatitis [Warburg effect may explain the mechanisms of the prognostic ability of De Ritis ratio. In the view of Warburg, there was mitochondrial dysfunction in tumor cells [Previous studies also indicated that lactate dehydrogenase, alkaline phosphatase, APRI, and ALRI were significant prognostic factors for metastatic CRC patients [Considering that individuals with hepatobiliary disorders may have abnormal levels of serum liver enzymes, which may influence the assessment of prognostic values of markers. Our study excluded CRC patients with fatty liver, cirrhosis, cholecystitis, gallstones, and gallbladder polyps. Although our study included patients with positive HBs-Ag and/or positive HCV-Ab, the prognostic values of markers were not affected due to the small proportion. Because postoperative treatment also has an important effect on prognosis, the prognostic effects of markers were adjusted by postoperative chemotherapy and radiotherapy in the multivariate Cox models.Nomograms are widely used in oncology and have been validated to compare favorably to the conventional TNM staging systems in many cancers [Compared with previous studies, our study systematically investigated and validated the prognostic role of lactate dehydrogenase, alkaline phosphatase, De Ritis ratio, APRI, ALRI, ANRI, and APPRI based on a cohort containing quite a large number of patients with stage II/III CRC. In addition, new prognosis prediction models incorporating De Ritis ratio and significant clinicopathological features, also have been successfully developed. The advantages of this study include not only exploring the serum biomarkers associated with the prognosis of stage II/III CRC patients but also performing personalized survival prediction, which could help clinicians to identify patients at high risk of recurrence and death. Our study also has several limitations. First, all the patients in the training and testing sets came from a single-center cohort, which may bring selection bias. Multi-center cohorts should be conducted to further validate the prognostic ability of De Ritis ratio and the universal application of the optimal cut-off values of De Ritis ratio. Second, this study was a retrospective cohort and it comes with a limitation that some data on clinicopathological features are lacking, such as lymphovascular invasion, tumor budding, tumor-infiltrating lymphocyte, and microsatellite instability.