Prognostic value of expression levels of miR‑148a, miR‑152 and HLA‑G in colon cancer

Emirzeoglu,Levent; Olmez,Ozgur; Mustafayev,Fatma Nihan Akkoc; Berber,Ufuk; Yilmaz,Ismail; Celik,Serkan; Oven,Bala Basak; Ozgun,Mehmet Alpaslan

doi:10.3892/ol.2022.13347

Prognostic value of expression levels of miR‑148a, miR‑152 and HLA‑G in colon cancer

Authors:
- Levent Emirzeoglu
- Ozgur Olmez
- Fatma Nihan Akkoc Mustafayev
- Ufuk Berber
- Ismail Yilmaz
- Serkan Celik
- Bala Basak Oven
- Mehmet Alpaslan Ozgun
View Affiliations

Affiliations: Department of Medical Oncology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey, Department of Pathology, University of Health Sciences, Sultan II. Abdulhamid Khan Educational and Research Hospital, 34660 Istanbul, Turkey, Department of Medical Oncology, Yeditepe University Koşuyolu Hospital, 34718 Istanbul, Turkey
Published online on: May 26, 2022 https://doi.org/10.3892/ol.2022.13347
Article Number: 226
Copyright: © Emirzeoglu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aberrant expression of human leukocyte antigen G (HLA‑G), an immunosuppressive molecule, has been observed in various cancer types. The exact mechanism of HLA‑G expression is unclear. HLA‑G expression is associated with low expression levels of microRNA (miR)‑148a and miR‑152. To the best of our knowledge, the prognostic value of the expression levels of miR‑148a, miR‑152 and HLA‑G has not been investigated in colon cancer. The aim of the present study was to investigate the relationship between the presence of HLA‑G molecules and the expression levels of miR‑148 and miR‑152 in colon cancer. In addition, the association of both HLA‑G and miR expression with survival results and clinicopathological data was determined. An immunohistochemical method was used for detection of HLA‑G expression in the tumor tissues and adjacent healthy tissues of 108 patients with colon cancer. Reverse transcription‑quantitative PCR was used for miR analysis. HLA‑G was expressed in 82 (75.9%) of the cancer samples, and there was no staining in normal tissues. HLA‑G expression >20%, which was found in 41.7% (45/108) of the patients with colon cancer, was significantly positively associated with patient survival (P=0.039). Additionally, miR‑148a levels were lower in the tumor tissues compared with the adjacent healthy tissues. No differences were found for miR‑152 expression. In addition, mir‑148a levels were found to be significantly lower (P=0.001) in HLA‑G‑positive tumor tissues than HLA‑G‑negative tumor tissues, but no such relationship was found for miR‑152 levels. The presence of HLA‑G expression was associated with poor survival outcomes. HLA‑G is one of the prognostic factors in colon cancer, and decreased miR‑148a expression in colon cancer tissues may be associated with HLA‑G‑mediated carcinogenesis.

View Figures

View References

1	Raskov H, Pommergaard HC, Burcharth J and Rosenberg J: Colorectal carcinogenesis-update and perspectives. World J Gastroenterol. 20:18151–18164. 2014. View Article : Google Scholar : PubMed/NCBI
2	Yi M, Xu L, Jiao Y, Luo S, Li A and Wu K: The role of cancer-derived microRNAs in cancer immune escape. J Hematol Oncol. 13:1–14. 2020. View Article : Google Scholar
3	Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ and DeMars R: A class I antigen, HLA-G, expressed in human trophoblasts. Science. 248:220–223. 1990. View Article : Google Scholar : PubMed/NCBI
4	Carosella ED, Moreau P, Le Maoult J, Le Discorde M, Dausset J and Rouas-Freiss N: HLA-G molecules: From maternal-fetal tolerance to tissue acceptance. Ad İmmunol. 81:199–252. 2003. View Article : Google Scholar : PubMed/NCBI
5	Tilburgs T, Evans JH, Crespo ÂC and Strominger JL: The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface. Proc Natl Acad Sci USA. 112:13312–13317. 2015. View Article : Google Scholar : PubMed/NCBI
6	Loustau M, Anna F, Dréan R, Lecomte M, Langlade-Demoyen P and Caumartin J: HLA-G neo-expression on tumors. Front Immunol. 11:16852020. View Article : Google Scholar : PubMed/NCBI
7	Carosella ED, Moreau P, LeMaoult J and Rouas-Freiss N: HLA-G: From biology to clinical benefits. Trends İmmunol. 29:125–132. 2008. View Article : Google Scholar : PubMed/NCBI
8	Favier B, LeMaoult J, Lesport E and Carosella ED: ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse. FASEB J. 24:689–699. 2010. View Article : Google Scholar : PubMed/NCBI
9	Morandi F, Ferretti E, Bocca P, Prigione I, Raffaghello L and Pistoia V: A novel mechanism of soluble HLA-G mediated immune modulation: Downregulation of T cell chemokine receptor expression and impairment of chemotaxis. PLoS One. 5:e117632010. View Article : Google Scholar : PubMed/NCBI
10	Calin GA and Croce CM: MicroRNA-cancer connection: The beginning of a new tale. Cancer Res. 66:7390–7394. 2006. View Article : Google Scholar : PubMed/NCBI
11	Yaghoubi N, Avval FZ, Khazaei M and Aghaee-Bakhtiari SH: MicroRNAs as potential investigative and predictive biomarkers in colorectal cancer. Cell Signal. 80:1099102021. View Article : Google Scholar : PubMed/NCBI
12	Manaster I, Goldman-Wohl D, Greenfield C, Nachmani D, Tsukerman P, Hamani Y, Yagel S and Mandelboim O: MiRNA-mediated control of HLA-G expression and function. PLoS One. 7:e333952012. View Article : Google Scholar : PubMed/NCBI
13	Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D and Ober C: Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet. 81:829–834. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zhu XM, Han T, Wang XH, Li YH, Yang HG, Luo YN, Yin GW and Yao YQ: Overexpression of miR-152 leads to reduced expression of human leukocyte antigen-G and increased natural killer cell mediated cytolysis in JEG-3 cells. Am J Obstet Gynecol. 202:592e1–7. 2010. View Article : Google Scholar : PubMed/NCBI
15	Peskoe SB, Barber JR, Zheng Q, Meeker AK, De Marzo AM, Platz EA and Lupold SE: Differential long-term stability of microRNAs and RNU6B snRNA in 12–20 year old archived formalin-fixed paraffin-embedded specimens. BMC Cancer. 17:1–7. 2017. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Chen Y, Song Y, Wang Z, Yue Z, Xu H, Xing C and Liu Z: Altered expression of MiR-148a and MiR-152 in gastrointestinal cancers and its clinical significance. J Gastrointest Surg. 14:1170–1179. 2010. View Article : Google Scholar : PubMed/NCBI
18	Zhou X, Zhao F, Wang ZN, Song YX, Chang H, Chiang Y and Xu HM: Altered expression of miR-152 and miR-148a in ovarian cancer is related to cell proliferation. Oncol Rep. 27:447–454. 2012.PubMed/NCBI
19	Zheng G, Xiong Y, Xu W, Wang Y, Chen F, Wang Z and Yan Z: A two-microRNA signature as a potential biomarker for early gastric cancer. Oncol Lett. 7:679–684. 2014. View Article : Google Scholar : PubMed/NCBI
20	Takahashi M, Cuatrecasas M, Balaguer F, Hur K, Toiyama Y, Castells A, Boland CR and Goel A: The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One. 7:e466842012. View Article : Google Scholar : PubMed/NCBI
21	Tsai HL, Yang IP, Huang CW, Ma CJ, Kuo CH, Lu CY, Juo SH and Wang JY: Clinical significance of microRNA-148a in patients with early relapse of stage II stage and III colorectal cancer after curative resection. Transl Res. 162:258–268. 2013. View Article : Google Scholar : PubMed/NCBI
22	Hanoun N, Delpu Y, Suriawinata AA, Bournet B, Bureau C, Selves J, Tsongalis GJ, Dufresne M, Buscail L, Cordelier P and Torrisani J: The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin Chem. 56:1107–1118. 2010. View Article : Google Scholar : PubMed/NCBI
23	Hummel R, Hussey DJ, Michael MZ, Haier J, Bruewer M, Senninger N and Watson DI: MiRNAs and their association with locoregional staging and survival following surgery for esophageal carcinoma. Ann Surg Oncol. 18:253–260. 2011. View Article : Google Scholar : PubMed/NCBI
24	Jasinski-Bergner S, Stoehr C, Bukur J, Massa C, Braun J, Hüttelmaier S, Spath V, Wartenberg R, Legal W, Taubert H, et al: Clinical relevance of miR-mediated HLA-G regulation and the associated immune cell infiltration in renal cell carcinoma. Oncoimmunology. 4:e10088052015. View Article : Google Scholar : PubMed/NCBI
25	Chen Q, Luo G and Zhang X: MiR-148a modulates HLA-G expression and influences tumor apoptosis in esophageal squamous cell carcinoma. Exp Ther Med. 14:4448–4452. 2017.PubMed/NCBI
26	Hansel DE, Rahman A, Wilentz RE, Shih IM, McMaster MT, Yeo CJ and Maitra A: HLA-G upregulation in pre-malignant and malignant lesions of the gastrointestinal tract. Internat J Gastrointest Cancer. 35:15–23. 2005. View Article : Google Scholar : PubMed/NCBI
27	Swets M, König MH, Zaalberg A, Dekker-Ensink NG, Gelderblom H, van de Velde CJ, van den Elsen PJ and Kuppen PJK: HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases. Hum İmmunol. 77:773–779. 2016. View Article : Google Scholar : PubMed/NCBI
28	Murdaca G, Calamaro P, Lantieri F, Pigozzi S, Mastracci L, Grillo F, Magnani O, Ceppa P, Puppo F and Fiocca R: HLA-G expression in gastric carcinoma: Clinicopathological correlations and prognostic impact. Virchows Arch. 473:425–433. 2018. View Article : Google Scholar : PubMed/NCBI
29	Shahraki PK, Alavian-Mehr A and Farjadian S: HLA-G: Facts and fictions. Asian Pac J Cancer Biol. 3:37–45. 2018. View Article : Google Scholar
30	Tuncel T, Karagoz B, Haholu A, Ozgun A, Emirzeoglu L, Bilgi O and Kandemir EG: Immunoregulatory function of HLA-G in gastric cancer. Asian Pac J Cancer Prev. 14:7681–7684. 2013. View Article : Google Scholar : PubMed/NCBI
31	Wang Y, Ye Z, Meng XQ and Zheng SS: Expression of HLA-G in patients with hepatocellular carcinoma. Hepatobiliary Pancreat Dis İnt. 10:158–163. 2011. View Article : Google Scholar : PubMed/NCBI
32	Peng Y, Xiao J, Li W, Li S, Xie B, He J and Liu C: Prognostic and clinicopathological value of human leukocyte antigen G in gastrointestinal cancers: A meta-analysis. Front Oncol. 11:6429022021. View Article : Google Scholar : PubMed/NCBI
33	Ishigami S, Natsugoe S, Miyazono F, Nakajo A, Tokuda K, Matsumoto M, Okumura H, Douchi T, Hokita S and Aikou T: HLA-G expression in gastric cancer. Anticancer Res. 26:2467–2472. 2006.PubMed/NCBI
34	Leelawat K, Engprasert S, Pongchai-rerk U, Suthipintawong C and Leardkamolkarn V: No expression of human leukocyte antigen G (HLA-G) in colorectal cancer cells. J Med Assoc Thai. 87:816–818. 2004.PubMed/NCBI
35	Reimers MS, Engels CC, Putter H, Morreau H, Liefers GJ, van de Velde CJ and Kuppen PJK: Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: A retrospective cohort study. BMC Cancer. 14:1–12. 2014. View Article : Google Scholar : PubMed/NCBI
36	Lin A, Chen HX, Zhu CC, Zhang X, Xu HH, Zhang JG, Wang Q, Zhou WJ and Yan WH: Aberrant human leucocyte antigen-G expression and its clinical relevance in hepatocellular carcinoma. J Cell Mol Med. 14:2162–2171. 2010. View Article : Google Scholar : PubMed/NCBI
37	Lin A, Zhang X, Zhou WJ, Ruan YY, Xu DP, Wang Q and Yan WH: Human leukocyte antigen-G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma. Int J Cancer. 129:1382–1390. 2011. View Article : Google Scholar : PubMed/NCBI
38	Farjadian S, Tabebordbar M, Mokhtari M, Safaei A, Malekzadeh M and Ghaderi A: HLA-G expression in tumor tissues and soluble HLA-G plasma levels in patients with gastrointestinal cancer. Asian Pac J Cancer Prev. 19:2731–2735. 2018.PubMed/NCBI
39	Zhang RL, Zhang X, Dong SS, Hu B, Han QY, Zhang JG, Zhou WJ, Lin A and Yan WH: Predictive value of different proportion of lesion HLA-G expression in colorectal cancer. Oncotarget. 8:107441–107451. 2017. View Article : Google Scholar : PubMed/NCBI
40	Ye SR, Yang H, Li K, Dong DD, Lin XM and Yie SM: Human leukocyte antigen G expression: As a significant prognostic indicator for patients with colorectal cancer. Mod Pathol. 20:375–383. 2017. View Article : Google Scholar : PubMed/NCBI
41	Guo ZY, Lv YG, Wang L, Shi SJ, Yang F, Zheng GX, Wen WH and Yang AG: Predictive value of HLA-G and HLA-E in the prognosis of colorectal cancer patients. Cell İmmunol. 293:10–16. 2015. View Article : Google Scholar : PubMed/NCBI