Abstract
Introduction: Low circulating cholesterol concentration is proven to be associated with elevated cancer mortality and incidence, especially in breast, prostate cancer and non-small cell lung carcinoma. However, the association between cholesterol levels and diffuse large B cell lymphoma (DLBCL) remains unsolved.It is also critical to seek some simple and valuable prognostic factors that could identify high-risk DLBCL patients.The aim of our study was to investigate the correlation between prediagnostic serum lipid profile and DLBCL, and the prognostic value of cholesterol levels in DLBCL survival.
Methods: Five hundred and fifty consecutive subjects with detailed serum lipid levels at DLBCL diagnosis between January 2002 and December 2016 were recruited. All the patients enrolled were treated with rituximab based chemoimmunotherapies. We excluded the patients taking any drugs known to affect lipid metabolism, those with metabolism-related diseases, liver diseases, or other types of cancer. In accordance with the manufacturer's standard value, we used the lower limits of normal of serum lipid profile for further survival analyses. Multivariate Cox regression analyses screened the prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver-operator characteristic curves and the corresponding areas under the curve (AUC) assessed the predictive accuracy of International Prognostic Index (IPI) and hypocholesterolemia.
Results: Decreased levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) were significantly associated with unfavorable PFS and OS in rituximab era (Figure 1a, b, c and d). Patients with concurrently low HDL-C and low LDL-C had the remarkably worse PFS and OS compared with those having only low HDL-C, only low LDL-C, and normal HDL-C and LDL-C. Mutivariate Cox regression analyses showed that synchronously low HDL-C together with low LDL-C was an independent prognostic indicator not only for PFS (HR=3.165; 95% CI: 2.312−4.332, p <0.001), but also for OS (HR=2.576; 95% CI: 1.754−3.783, p <0.001). DLBCL patients who achieved complete remission or partial remission after 6−8 circles of chemotherapies had significantly increased TC, HDL-C and LDL-C levels compared with the cholesterol levels at DLBCL diagnosis, and HDL-C or LDL-C elevations were strongly correlated with better survival. Furthermore, we introduced a novel Prognostic Index (PI) which was calculated as the sum of IPI and one additional point for synchronously low HDL-C and LDL-C weighed by their Cox regression coefficients. PI demonstrated significantly larger AUCs than IPI alone and could accurately differentiate the survival outcomes of DLBCL patients. It can serve as a better predictive index in PFS and OS for both short-term and long-term prognosis of DLBCL (Figure 1e, f, g and h).
Conclusions: Serum cholesterol levels are simple and routinely tested parameters, which may be a good candidate for predicting prognosis in future clinical practice of DLBCL.
No relevant conflicts of interest to declare.
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