Evaluation of sterol‑o‑acyl transferase 1 and cholesterol ester levels in plasma, peritoneal fluid and tumor tissue of patients with endometrial cancer: A pilot study

Ayyagari,Vijayalakshmi N.; Ayyagari,Vijayalakshmi N.; Li,Miao; Li,Miao; Diaz-Sylvester,Paula; Diaz-Sylvester,Paula; Groesch,Kathleen; Groesch,Kathleen; Wilson,Teresa; Wilson,Teresa; Pasman,Zvi; Pasman,Zvi; Shah,Ejaz M.; Shah,Ejaz M.; Braundmeier-Fleming,Andrea; Braundmeier-Fleming,Andrea; Brard,Laurent; Brard,Laurent

doi:10.3892/ol.2023.13817

Evaluation of sterol‑o‑acyl transferase 1 and cholesterol ester levels in plasma, peritoneal fluid and tumor tissue of patients with endometrial cancer: A pilot study

Authors:
- Vijayalakshmi N. Ayyagari
- Miao Li
- Paula Diaz-Sylvester
- Kathleen Groesch
- Teresa Wilson
- Zvi Pasman
- Ejaz M. Shah
- Andrea Braundmeier-Fleming
- Laurent Brard
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Affiliations: Department of Obstetrics and Gynecology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA, Department of Chemistry, Illinois College, Jacksonville, IL 62650, USA
Published online on: April 18, 2023 https://doi.org/10.3892/ol.2023.13817
Article Number: 231
Copyright: © Ayyagari et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometrial cancer (EC) is the most prevalent gynecological malignancy. Abnormal accumulation of sterol‑O‑acyl transferase 1 (SOAT1) and SOAT1‑mediated cholesterol ester (CE) contributes to cancer progression in various malignancies, including ovarian cancer. Therefore, it was hypothesized that similar molecular changes may occur in EC. The present study aimed to evaluate the diagnostic and/or prognostic potential of SOAT1 and CE in EC by: i) Determining SOAT1 and CE levels in plasma, peritoneal fluid and endometrial tissue from patients with EC and control subjects; ii) performing receiver operating characteristic curve analysis to determine diagnostic performance; iii) comparing SOAT1 and CE expression to that of the tumor proliferation marker Ki67; and iv) assessing the association between SOAT1 expression and survival. Enzyme‑linked immunosorbent assay was used to determine the levels of SOAT1 protein in tissue, plasma and peritoneal fluid. The mRNA and protein expression levels of SOAT1 and Ki67 in tissues were detected by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry, respectively. CE levels were determined colorimetrically in plasma and peritoneal fluid. SOAT1‑associated survival data from the cBioPortal cancer genomics database were used to assess prognostic relevance. The results revealed that SOAT1 and CE levels were significantly elevated in tumor tissue and peritoneal fluid samples collected from the EC group. By contrast, the plasma levels of SOAT1 and CE in the EC and control groups were similar. Significant positive associations between CE and SOAT1, SOAT1/CE and Ki67, and SOAT1/CE and poor overall survival in patients with EC suggested that SOAT1/CE may be associated with malignancy, aggressiveness and poor prognosis. In conclusion, SOAT1 and CE may serve as potential biomarkers for prognosis and target‑specific treatment of EC.

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1	Bendifallah S, Canlorbe G, Raimond E, Hudry D, Coutant C, Graesslin O, Touboul C, Huguet F, Cortez A, Daraï E and Ballester M: A clue towards improving the European society of medical oncology risk group classification in apparent early stage endometrial cancer? Impact of lymphovascular space invasion. Br J Cancer. 110:2640–2646. 2014. View Article : Google Scholar : PubMed/NCBI
2	Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, Marth C, Nout R, Querleu D, Mirza MR, et al: ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Ann Oncol. 27:16–41. 2016. View Article : Google Scholar : PubMed/NCBI
3	Gilks CB, Oliva E and Soslow RA: Poor interobserver reproducibility in the diagnosis of high-grade endometrial carcinoma. Am J Surg Pathol. 37:874–881. 2013. View Article : Google Scholar : PubMed/NCBI
4	Aghajanian C, Filiaci V, Dizon DS, Carlson JW, Powell MA, Secord AA, Tewari KS, Bender DP, O'Malley DM, Stuckey A, et al: A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer. Gynecol Oncol. 150:274–281. 2018. View Article : Google Scholar : PubMed/NCBI
5	Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, et al: Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol. 38:2981–2992. 2020. View Article : Google Scholar : PubMed/NCBI
6	Chang TY, Li BL, Chang CC and Urano Y: Acyl-coenzyme A: Cholesterol acyltransferases. Am J Physiol Endocrinol Metab. 297:E1–E9. 2009. View Article : Google Scholar : PubMed/NCBI
7	Danilo C, Gutierrez-Pajares JL, Mainieri MA, Mercier I, Lisanti MP and Frank PG: Scavenger receptor class B type I regulates cellular cholesterol metabolism and cell signaling associated with breast cancer development. Breast Cancer Res. 15:R872013. View Article : Google Scholar : PubMed/NCBI
8	Paillasse MR, de Medina P, Amouroux G, Mhamdi L, Poirot M and Silvente-Poirot S: Signaling through cholesterol esterification: A new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion. J Lipid Res. 50:2203–2211. 2009. View Article : Google Scholar : PubMed/NCBI
9	Tosi MR and Tugnoli V: Cholesteryl esters in malignancy. Clin Chim Acta. 359:27–45. 2005. View Article : Google Scholar : PubMed/NCBI
10	Mayengbam SS, Singh A, Pillai AD and Bhat MK: Influence of cholesterol on cancer progression and therapy. Transl Oncol. 14:1010432021. View Article : Google Scholar : PubMed/NCBI
11	Antalis CJ, Arnold T, Rasool T, Lee B, Buhman KK and Siddiqui RA: High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation. Breast Cancer Res Treat. 122:661–670. 2010. View Article : Google Scholar : PubMed/NCBI
12	Bemlih S, Poirier MD and El Andaloussi A: Acyl-coenzyme A: Cholesterol acyltransferase inhibitor avasimibe affect survival and proliferation of glioma tumor cell lines. Cancer Biol Ther. 9:1025–1032. 2010. View Article : Google Scholar : PubMed/NCBI
13	Yue S, Li J, Lee SY, Lee HJ, Shao T, Song B, Cheng L, Masterson TA, Liu X, Ratliff TL and Cheng JX: Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 19:393–406. 2014. View Article : Google Scholar : PubMed/NCBI
14	Li J, Gu D, Lee SS, Song B, Bandyopadhyay S, Chen S, Konieczny SF, Ratliff TL, Liu X, Xie J and Cheng JX: Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene. 35:6378–6388. 2016. View Article : Google Scholar : PubMed/NCBI
15	Ayyagari VN, Wang X, Diaz-Sylvester PL, Groesch K and Brard L: Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression-an in vitro study. PLoS One. 15:e02280242020. View Article : Google Scholar : PubMed/NCBI
16	de Gonzalo-Calvo D, López-Vilaró L, Nasarre L, Perez-Olabarria M, Vázquez T, Escuin D, Badimon L, Barnadas A, Lerma E and Llorente-Cortés V: Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: A molecular and clinicopathological study. BMC Cancer. 15:4602015. View Article : Google Scholar : PubMed/NCBI
17	Ayyagari V, Li M, Pasman Z, Wang X, Louis S, Diaz-Sylvester P, Groesch K, Wilson T and Brard L: Assessment of the diagnostic and prognostic relevance of ACAT1 and CE levels in plasma, peritoneal fluid and tumor tissue of epithelial ovarian cancer patients-a pilot study. BMC Cancer. 22:3872022. View Article : Google Scholar : PubMed/NCBI
18	Secord AA, Hasselblad V, Von Gruenigen VE, Gehrig PA, Modesitt SC, Bae-Jump V and Havrilesky LJ: Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol. 140:184–190. 2016. View Article : Google Scholar : PubMed/NCBI
19	Miao R, Badger TC, Groesch K, Diaz-Sylvester PL, Wilson T, Ghareeb A, Martin JA, Cregger M, Welge M, Bushell C, et al: Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer. PLoS One. 15:e02277072020. View Article : Google Scholar : PubMed/NCBI
20	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
21	Piulats JM, Guerra E, Gil-Martín M, Roman-Canal B, Gatius S, Sanz-Pamplona R, Velasco A, Vidal A and Matias-Guiu X: Molecular approaches for classifying endometrial carcinoma. Gynecol Oncol. 145:200–207. 2017. View Article : Google Scholar : PubMed/NCBI
22	Cramer DW: The epidemiology of endometrial and ovarian cancer. Hematol Oncol Clin North Am. 26:1–12. 2012. View Article : Google Scholar : PubMed/NCBI
23	Merritt MA and Cramer DW: Molecular pathogenesis of endometrial and ovarian cancer. Cancer Biomark. 9:287–305. 2010. View Article : Google Scholar : PubMed/NCBI
24	Omsjø IH and Norum KR: Cholesterol esterification in human secretory endometrium and in endometrial cancer tissue. Demonstration of microsomal acyl-CoA-cholesterol acyl-transferase (ACAT) activity. Acta Obstet Gynecol Scand. 64:473–476. 1985. View Article : Google Scholar : PubMed/NCBI
25	Odagiri T, Watari H, Hosaka M, Mitamura T, Konno Y, Kato T, Kobayashi N, Sudo S, Takeda M, Kaneuchi M and Sakuragi N: Multivariate survival analysis of the patients with recurrent endometrial cancer. J Gynecol Oncol. 22:3–8. 2011. View Article : Google Scholar : PubMed/NCBI
26	Sahoo SS, Zhang XD, Hondermarck H and Tanwar PS: The emerging role of the microenvironment in endometrial cancer. Cancers (Basel). 10:4082018. View Article : Google Scholar : PubMed/NCBI
27	Hanahan D and Coussens LM: Accessories to the crime: Functions of cells recruited to the tumor microenvironment. Cancer cell. 21:309–322. 2012. View Article : Google Scholar : PubMed/NCBI
28	Rana SV, Babu SG and Kocchar R: Usefulness of ascitic fluid cholesterol as a marker for malignant ascites. Med Sci Monit. 11:Cr136–Cr142. 2005.PubMed/NCBI
29	Tabas I: Consequences of cellular cholesterol accumulation: Basic concepts and physiological implications. J Clin Invest. 110:905–911. 2002. View Article : Google Scholar : PubMed/NCBI
30	Li J, Qu X, Tian J, Zhang JT and Cheng JX: Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation. PLoS One. 13:e01933182018. View Article : Google Scholar : PubMed/NCBI
31	Liu L, Xu HX, Wang WQ, Wu CT, Chen T, Qin Y, Liu C, Xu J, Long J, Zhang B, et al: Cavin-1 is essential for the tumor-promoting effect of caveolin-1 and enhances its prognostic potency in pancreatic cancer. Oncogene. 33:2728–2736. 2014. View Article : Google Scholar : PubMed/NCBI
32	Lee HJ, Li J, Vickman RE, Li J, Liu R, Durkes AC, Elzey BD, Yue S, Liu X, Ratliff TL and Cheng JX: Cholesterol esterification inhibition suppresses prostate cancer metastasis by impairing the Wnt/β-catenin pathway. Mol Cancer Res. 16:974–985. 2018. View Article : Google Scholar : PubMed/NCBI
33	Scott CC, Vossio S, Vacca F, Snijder B, Larios J, Schaad O, Guex N, Kuznetsov D, Martin O, Chambon M, et al: Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis. EMBO Rep. 16:741–752. 2015. View Article : Google Scholar : PubMed/NCBI
34	Goad J, Ko YA, Kumar M, Jamaluddin MFB and Tanwar PS: Oestrogen fuels the growth of endometrial hyperplastic lesions initiated by overactive Wnt/β-catenin signalling. Carcinogenesis. 39:1105–1116. 2018. View Article : Google Scholar : PubMed/NCBI
35	Liu Y, Meng F, Xu Y, Yang S, Xiao M, Chen X and Lou G: Overexpression of Wnt7a is associated with tumor progression and unfavorable prognosis in endometrial cancer. Int J Gynecol Cancer. 23:304–311. 2013. View Article : Google Scholar : PubMed/NCBI
36	Coopes A, Henry CE, Llamosas E and Ford CE: An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target. Endocr Relat Cancer. Aug 9–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
37	Wang Y, Hanifi-Moghaddam P, Hanekamp EE, Kloosterboer HJ, Franken P, Veldscholte J, van Doorn HC, Ewing PC, Kim JJ, Grootegoed JA, et al: Progesterone inhibition of Wnt/beta-catenin signaling in normal endometrium and endometrial cancer. Clin Cancer Res. 15:5784–5793. 2009. View Article : Google Scholar : PubMed/NCBI
38	Yoshioka S, King ML, Ran S, Okuda H, MacLean JA II, McAsey ME, Sugino N, Brard L, Watabe K and Hayashi K: WNT7A regulates tumor growth and progression in ovarian cancer through the WNT/β-catenin pathway. Mol Cancer Res. 10:469–482. 2012. View Article : Google Scholar : PubMed/NCBI
39	Hultsch S, Kankainen M, Paavolainen L, Kovanen RM, Ikonen E, Kangaspeska S, Pietiäinen V and Kallioniemi O: Association of tamoxifen resistance and lipid reprogramming in breast cancer. BMC Cancer. 18:8502018. View Article : Google Scholar : PubMed/NCBI
40	Liscovitch M and Lavie Y: Multidrug resistance: A role for cholesterol efflux pathways? Trends Biochem Sci. 25:530–534. 2000. View Article : Google Scholar : PubMed/NCBI