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

Abstract

An increasing amount of evidence suggests that high-density lipoprotein cholesterol (HDL-C) is related to a positive prognosis in various cancers. However, the correlation between HDL-C and the immune signature and the prognostic role of HDL-C in stage II/III colorectal cancer (CRC) has not been previously reported. A total of 667 CRC patients were enrolled and divided into two groups based on the lower limit of normal HDL-C values (0.78 mmol/L). We used Kaplan-Meier curves and the Cox regression model to analyze the prognostic role of HDL in both disease-free survival (DFS) and overall survival (OS). Fifty-five pairs of tumor tissues were selected according to the variation in HDL-C levels (high or low) and the matched characterizes (ages, T stage, and N stage). Using immunohistochemistry, tumor tissues were stained with antibodies against CD3, CD8, CD163, iNOS, Forkhead box P3 (FOXP3), and CD33. We calculated the density of positively-stained infiltrating cells in the tumor center (TC) and invasive margin (IM). We then used Spearman rank correlation to further investigate the relationship between HDL-C levels and the immune signatures. Our results revealed that compared to patients with high HDL-C levels, patients with low HDL-C levels had poor 3-year DFS (68.9% vs 83.1%, P = 0.032) and 5-year OS rates (66.6% vs 85.3%, P = 0.002). We also identified a positive correlation between HDL-C and CD3⁺ , CD8⁺ and iNOS⁺ cells and a negative correlation between HDL-C and CD163⁺ cells in both the TC and IM. This study reveals that a low HDL-C level in stage II/III CRC patients predicts poor prognosis. The correlation between the HDL-C level and immune signature in tissue specimens suggested that HDL-C is likely to play an inhibitory role in tumor development via affecting immune responses.

Keywords: HDL-C; colorectal cancer; immune signature.

Figure 1

Disease‐free (DFS) and overall survival (OS) between patients with high and low HDL‐C levels. Patients with high HDL‐C levels presented with an improved DFS and OS

Figure 2

Representative pictures of low‐and high‐density CD3⁻, CD8⁻, CD163⁻, iNOS⁻, FOXP3⁻ and CD33‐positive cells in the tumor center (TC) and invasive margin (IM)

Figure 3

Correlation between HDL level and the immune signature. (A) Analysis of the positive correlation between HDL levels and CD3⁺ cells in the TC; (B) Analysis of the positive correlation between HDL levels and CD3⁺ cells in the IM; (C) Analysis of the positive correlation between HDL levels and CD8⁺ cells in the TC; (D) Analysis of the positive correlation between HDL levels and CD8⁺ cells in the IM; (E) Analysis of the correlation between HDL levels and CD163⁺ cells in the TC; (F) Analysis of the correlation between HDL levels and CD163⁺ cells in the IM; (G) Analysis of the correlation between HDL levels and iNOS⁺ cells in the TC; (H) Analysis of the correlation between HDL levels and iNOS⁺ cells in the IM; (I) Analysis of the correlation between HDL levels and FOXP3⁺ cells in the TC; (J) Analysis of the correlation between HDL levels and FOXP3⁺ cells in the IM; (K) Analysis of the correlation between HDL levels and CD33⁺ cells in the TC; (L) Analysis of the correlation between HDL levels and CD33⁺ cells in the IM