Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep 12;20(1):104.
doi: 10.1186/s12944-021-01539-0.

Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study

Ryuk Jun Kwon  1 , Eun-Ju Park  1 , Sang Yeoup Lee  1 , Youngin Lee  1 , Chungsu Hwang  2 , Choongrak Kim  3 , Young Hye Cho  4
Affiliations

Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study

Ryuk Jun Kwon et al. Lipids Health Dis. .

Abstract

Background: Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown.

Methods: Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann-Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC.

Results: The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan-Meier and multivariate regression analyses.

Conclusions: As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.

Keywords: Cholesterol; Colorectal cancer; Ezetimibe; Molecular marker; Niemann-Pick C1-Like 1; Overall survival; Prognosis; Stage.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart for obtaining information for CRC patients with normal NPC1L1 expression
Fig. 2
Fig. 2
NPC1L1 expression in normal and CRC tissues. a NPC1L1 expression in CRC tissues as compared to that in normal tissues is presented as a box and whisker plot format. The numbers of normal and tumor tissues analyzed were 50 and 440, respectively. The mean value of NPC1L1 expression in normal tissues (blue box) was 7.00 and that in CRC tissues (red box) was 130.09. Significance was evaluated using the Mann–Whitney U test (P < 0.001). b Relative expression levels of NPC1L1 in tumor tissues (CRC) as compared to those in paired normal tissues are presented as a bar graph. The numbers of tumor and paired normal tissues analyzed were 35 (each). c NPC1L1 expression in CRC tissues as compared to that in normal tissues (GSE9348) is presented as a box and whisker plot format. The numbers of normal and tumor tissues analyzed were 12 and 70, respectively. The mean value of NPC1L1 expression in normal tissues (blue box) was 22.69 and that in CRC tissues (red box) was 81.35. Significance was evaluated using the Mann–Whitney U test (P = 0.014).
Fig. 3
Fig. 3
Kaplan–Meier survival analysis based on the expression level of NPC1L1. a Kaplan–Meier curve based on TCGA dataset. The blue line indicates the group with low NPC1L1 expression, and the red line indicates the group with high NPC1L1expression. The 75th percentiles of low and high NPC1L1 expression groups were 4.12 and 2.35 years, respectively. The P value was calculated using the log-rank method and was significant (P< 0.021). b, c Kaplan–Meier curve based on the GEO dataset (GSE17536 and GSE12945). The cutoff point was obtained using a ROC curve. The blue line indicates the group with low NPC1L1 expression, and the red line indicates the group with high NPC1L1 expression. The P value was calculated by the log-rank method and was significant (GSE17536, P = 0.036; GSE12945, P = 0.049)
Fig. 4
Fig. 4
Kaplan–Meier survival analysis after applying a combination of prognostic factors. The stage (low: I + II vs. high: III + IV), age (low: < 70 vs. high: ≥ 70), and NPC1L1 (low expression vs. high expression) groups were each divided into two groups. Then, survival analysis was performed by combining prognostic factors. The red line indicates a high stage and/or high NPC1L1 expression and/or older age group. The blue line indicates a low stage and/or low NPC1L1 expression and/or younger age group. The green line indicates mixed combination groups, excluding all high and all low combination groups. a Stage-only group. b NPC1L1 and stage group. c Stage and age group. d NPC1L1, stage, and age group
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490–502. doi: 10.1016/S0140-6736(13)61649-9. - DOI - PubMed
    1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91. doi: 10.1136/gutjnl-2015-310912. - DOI - PubMed
    1. Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366–78. doi: 10.3322/caac.20038. - DOI - PubMed
    1. Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14:89–103. - PMC - PubMed
    1. Jacobs RJ, Voorneveld PW, Kodach LL, Hardwick JC. Cholesterol metabolism and colorectal cancers. Curr Opin Pharmacol. 2012;12:690–5. doi: 10.1016/j.coph.2012.07.010. - DOI - PubMed

MeSH terms

-