Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development

Abstract

IntroductionDyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy.Materials and methodsThis case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods.ResultsTotal cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P < 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P < 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P < 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%).ConclusionsPatients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development.

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

“…Although significant discrepancy among human and mouse resistin prevents deriving definitive conclusions, these findings suggest that elevation of circulating resistin levels in humans might arise as a consequence of decreased HDL-C and impaired HDL particle functionality. In our previous study, we demonstrated that HDL particle distribution in patients with CRC is characterized by lower diameter and increased proportion of smaller HDL3b particles, implying compromised HDL functionality [13]. Accordingly, in the current study, we found a change in PON-1 activity across tertiles of HDL-C (Fig.…”

“…This research was designed as a part of a larger project that investigated interactive role of dyslipidemia, oxidative stress, and inflammation in CRC, enrolling 126 patients as previously reported [12,13]. Patients were recruited from the Clinic of General Surgery, Military Medical Academy in Belgrade from July 2014 to January 2016.…”

“…The relationship of resistin with high-density lipoprotein (HDL) particles might be especially intriguing, since this lipoprotein is a significant contributor to anti-inflammatory and anti-oxidative capacities of plasma. We have previously demonstrated alterations of high-density lipoprotein (HDL) particles maturation, antioxidative capacity [12], and structure [13] in CRC. Nevertheless, possible associations of resistin with HDL cholesterol (HDL-C) concentration and paraoxonase-1 (PON-1) activity, which is an indicator of HDL's protective properties, are still unexplored in this pathological condition.…”

Paraoxonase 1 and atherosclerosis‐related diseases

“…112 Additionally, we demonstrated in CRC patients that the distribution of HDL particles was shifted toward smaller and less functional HDL 3b particles. 113 Such inefficient maturation could have arisen as a consequence of lower activity of LCAT and higher CETP activity, resulting in the generation of smaller HDL particles enriched in triglycerides. 112 In addition, due to inefficient PON1 activity, a lack of protective effects against oxidative modification of HDL and LDL particles was likely.…”

Correlation between immune signature and high‐density lipoprotein cholesterol level in stage II/III colorectal cancer

“…Apolipoprotein A‐I (ApoA‐I), the predominant protein in HDL‐C, has also been observed to be positively related to survival. In CRC patients, the level of HDL‐C was significantly lower compared to that in the health controls . CRC patients with metastases had substantially higher levels of low‐density lipoprotein cholesterol (LDL‐C) and LDL‐C to HDL‐C ratio than early‐stage patients .…”