Endothelial dysfunction in cancer patients before and after chemotherapy: focus on biomarkers

Type of funding sources: Foundation. Main funding source(s): The reported study was funded by Russian Foundation for Basic Research (RFBR) project number 19-315-90034

Background. Nowadays gastric cancer is one of the leading causes of world cancer mortality. Modern chemotherapy (CT) significantly improves survival and quality of life among these patients. Unfortunately, anticancer drugs induce some biomolecular disorders, which influence endothelial dysfunction and microcirculation lesions, subsequently leading to vasculo- and cardiotoxicity.

To study the dynamics of endothelial dysfunction’s (ED) biomarkers (endothelin-1 (ET-1), von Willebrand factor (VWF)) in patients with gastric cancer before and after CT.

The study included 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage II - IV, who have been treated by CT including platinum compound (oxaliplatin, cisplatin) and fluoropyrimidine group (5-fluorouracil, capecitabine) and are proven to be cardiovasculotoxic. All patients underwent blood tests, computer nailfold capillaroscopy and finger photoplethysmography (non-invasive assessment of vascular wall stiffness and endothelial function), electrocardiography (ECG), 24-hour ECG, echocardiography before CT and within a month after the last course.

The median patients’ age was 64 ± 13 years; 68% were male; 52% had a prior cardiac illness: arterial hypertension (n = 12, 48%), coronary artery disease (n = 7, 28%), chronic heart failure (n = 3, 12%). The data obtained showed that ET-1 median levels were below normal values and did not change during CT: 0,95pg/ml (0,6;1,4) vs. 0,94pg/ml (0,7;1,4), р<0,9 (N = 1–3pg/ml), before and after CT respectively. The level of VWF remained within normal ranges and did not significantly differ in cancer patients before and after treatment 0,75IU/ml (0,7;0,9) vs. 0,8IU/ml (0,74;0,9), р<0,6 (N = 0,5–1,5IU/ml). Even before CT, endothelial dysfunction was detected, which significantly worsened after the treatment (occlusion index (IO) before and after CT 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p < 0.0002, respectively). During data analysis, significant correlations were found: between ET-1 level and IO (r = 0.554, p = 0,006), ET-1 and percentage of capillary recovery (r= -0.7, p = 0,029) [both parameters characterize functional abnormalities of the microvasculature], ET-1 and the quantity of supraventricular extrasystoles (r=-0.48, p = 0,032).

In this study, the dynamics of ED biomarkers in patients with gastric cancer were studied. Even though reliable changes were not proven for the assessed molecular parameters ET-1 and VWF during CT (supposing depletion of endothelin system, small patient cohort), the above parameters may be used for identifying early signs of close and long-term cardio/vasculotoxicity due to significant positive correlations with microvasculature lesions. Further bigger trials for identification of other accurate and effective laboratory methods of detecting early features of vasculotoxicity are required.