Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 16, 2022; 10(14): 4446-4459
Published online May 16, 2022. doi: 10.12998/wjcc.v10.i14.4446
Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer
Jin-Hua Tao, Xiao-Tong Wang, Wei Yuan, Jia-Nan Chen, Zhi-Jie Wang, Yun-Bin Ma, Fu-Qiang Zhao, Liu-Yuan Zhang, Jie Ma, Qian Liu
Jin-Hua Tao, Jia-Nan Chen, Zhi-Jie Wang, Fu-Qiang Zhao, Qian Liu, Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Xiao-Tong Wang, Wei Yuan, Liu-Yuan Zhang, Jie Ma, State Key Laboratory of Molecular Oncology, Clinical Immunology Center, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Yun-Bin Ma, Department of Abodominal Surgery, Beijing Sanhuan Cancer Hospital, Beijing 100122, China
Author contributions: Tao JH, Wang XT, Yuan W, Ma J, and Liu Q designed the research; Chen JN, Wang ZJ, Ma YB, Zhao FQ, and Zhang LY collected the data; Tao JH, Wang XT, and Yuan W analyzed the data; Tao JH, and Wang XT wrote the paper; and All authors contributed to this manuscript.
Institutional review board statement: The current research was approved by the Institutional Review Board.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qian Liu, MD, Chief Doctor, Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. fcwpumch@163.com
Received: March 8, 2022
Peer-review started: March 8, 2022
First decision: March 24, 2022
Revised: March 27, 2022
Accepted: April 20, 2022
Article in press: April 20, 2022
Published online: May 16, 2022
Abstract
BACKGROUND

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract. Lipid metabolism, as an important part of material and energy circulation, is well known to play a crucial role in CRC.

AIM

To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.

METHODS

We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects. The levels of serum total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS. Then, we used the data from Oncomine to screen the differentially expressed genes (DEGs) of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs. PrognoScan was used to analyze the prognostic value of the DEGs, and Search Tool for the Retrieval of Interacting Genes was used to construct the protein–protein interaction network of DEGs.

RESULTS

The serum HDL-C level in CRC patients was significantly correlated with tumor size, and patients whose tumor size was more than 5 cm had a lower serum HDL-C level (1.18 ± 0.41 mmol/L vs 1.25 ± 0.35 mmol/L, P < 0.01) than their counterparts. In addition, TC/HDL (4.19 ± 1.33 vs 3.93 ± 1.26, P < 0.01) and LDL-C/HDL-C (2.83 ± 1.10 vs 2.61 ± 0.96, P < 0.01) were higher in patients with larger tumors. The levels of HDL-C (P < 0.05), TC/HDL-C (P < 0.01) and LDL-C/HDL-C (P < 0.05) varied in different stages of CRC patients, and the differences were significant. We screened 14 differentially expressed genes (DEGs) of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8 (LRP8), PCSK9, low-density lipoprotein receptor (LDLR), MBTPS2 and FDXR are upregulated, while ABCA1 and OSBPL1A are downregulated in cancer tissue. Higher expression of LDLR (HR = 3.12, 95%CI: 1.77-5.49, P < 0.001), ABCA1 (HR = 1.66, 95%CI: 1.11-2.48, P = 0.012) and OSBPL1A (HR = 1.38, 95%CI: 1.01-1.89, P = 0.041) all yielded significantly poorer DFS outcomes. Higher expression of FDXR (HR = 0.7, 95%CI: 0.47-1.05, P = 0.002) was correlated with longer DFS. LDLR, ABCA1, OSBPL1A and FDXR were involved in many important cellular function pathways.

CONCLUSION

Serum HDL-C levels are associated with tumor size and stage in CRC patients. LRP8, PCSK9, LDLR, MBTPS2 and FDXR are upregulated, while ABCA1 and OSBPL1A are downregulated in CRC. Among them, LDLR, ABCA1, OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

Keywords: Colorectal cancer, High-density lipoprotein cholesterol, Cholesterol metabolism, Prognosis

Core Tip: Cholesterol metabolism is closely related to colorectal cancer (CRC). In this study, we explored the association between serum high-density lipoprotein cholesterol and tumor characteristics in patients with CRC, identified differentially expressed genes in the cholesterol metabolism pathway and analyzed the prognostic value of these differentially expressed genes in CRC. These findings provide clues for further research on cholesterol metabolism and CRC.