Effects of sleeve gastrectomy on N6-methyladenosine modification in duodenal tissue

Year 2023, Volume: 48 Issue: 4, 1365 - 1373, 29.12.2023

Badel Arslan , Hakan Seyit , Murat Eser Akyürek , Serdal Arslan , Damlanur Sakız , Çağatay Han Türkseven

https://doi.org/10.17826/cumj.1370487

Abstract

Purpose. In this study, the expression levels of METTL3, METTL14; and WTAP genes involved in the N6-methyladenosine (m6A) pathway, regulating cellular processes including cell renewal, differentiation, invasion; and apoptosis, were investigated in duodenal tissue after sleeve gastrectomy (SG).
Material and Methods: Duodenal biopsies were obtained from 24 obese patients before (BG) and 6 months after (AG) sleeve gastrectomy. Pathological evaluation was performed by H&E staining. Expression levels of METTL14, METTL3, and WTAP genes were analysed by Real-Time PCR.
Results: The METTL14 gene was significantly increased after surgery (BG-AG Median (Q1-Q3): 0.36 [0.07-1.52]-9.83 [0.20-68.12]). METTL3 (BG-AG Median (Q1-Q3): 0.49 [0.32-0.84]-0.67 [0.36-20.5]) and WTAP (BG-AG Median (Q1-Q3): 0.95 [0.17-7.65]-5.54 [2.34-66.07]) gene expressions were not altered. However, a strong positive (r=0.692) and significant relationship was found between METTL3 and WTAP. Chronic inflammation 81.32 %, intestinal metaplasia 10.54 %, activity 68.88 %, atrophy 5.32 %. No malignant findings were detected.
Conclusion: For the first time, we demonstrated that sleeve gastrectomy may increase the expression of the METTL14 gene involved in the m6A-methyladenosine pathway in duodenum. This alteration may lead to gastrointestinal tract diseases.

Keywords

Sleeve Gastrectomy, Bariatric Surgery, Epigenetic, Duodenum, N6-Methyladenosine

Supporting Institution

This study was supported by the authors.

Duodenal dokuda N6-metiladenozin modifikasyonu üzerine sleeve gastrektomi etkileri

Abstract

Amaç: Bu retrospektif çalışmada açık kalp cerrahisi geçiren 80 yaş üstü hastaların operasyon öncesi albümin değeri kullanılarak hesaplanan geriatrik nutrisyonel risk indeksinin, ameliyat sonrası mortalite oranını tahmin edebilme gücü ortaya konulmaya çalışıldı.
Gereç ve Yöntem: Temmuz 2019 – Eylül 2022 tarihleri arasında koroner bypass ve kalp kapağı değişimi nedeniyle açık elektif kalp cerrahisi uygulanan toplam 22 hasta (13 erkek, 9 kadın; ortalama yaş: 82,1±2,4 yıl; dağılım, 80-88 yıl) geriatrik nutrisyonel risk indeksi ile retrospektif olarak incelendi. Bu indekse göre iki grup oluşturuldu. 98 ve altındaki değerler riskli, 99 ve üstündeki değerler risksiz grup olarak belirlendi. Riskli grupta 6 hasta vardı. Diğer 16 hasta risksiz grupta bulunuyordu. Tüm hasta grubu cerrahi işlemler, cinsiyet, yaş, vücut kütle indeksi (kg/m2), atrial fibrilasyon, diyabet, hipertansiyon, sigara içiciliği ve operatif özellikler yönüyle karşılaştırıldı.
Bulgular: Çalışmada geriatrik nutrisyonel risk indeksine göre 6 riskli (%27,3) ve 16 risksiz (%72,7) hasta incelendi ve risk varlığı tespit edilen hastalarda mortalite oranı yüksek (%66,7) bulundu. Risk grubundaki hastalar, risk grubu olmayanlara kıyasla daha düşük vücut kitle indeksi ve albümin değerlerine sahipti (sırasıyla 25,0±1,8 ve 30,1±2,4; 28,1±2,4 ve 36,7±3,1). Ayrıca, ortalama entübasyon değerlerinin yüksek bulunduğu belirlendi (11,2±4,2). Diğer parametreler ile risk varlığı arasında anlamlı bir farklılığa rastlanılmadı.
Sonuç: Açık kalp cerrahisi öncesi değerlendirilen geriatrik nutrisyonel risk indeksi, operasyon sonrası mortalite oranını öngörmede güçlü bir belirleyici olarak kullanılabilir.

Keywords

Geriatrik nutrisyonel risk indeksi, oktogenarian, albümin, malnütrisyon

References

• Zhai Z, Li G, Tao Y, Wang Z, Han J. Sleeve gastrectomy plus uncut jejunojejunal bypass for the treatment of obesity and type 2 diabetes. Chin Med J. 2022;135:2240-1.
• Gagner M. Effect of sleeve gastrectomy on type 2 diabetes as an alternative to Roux-en-Y gastric bypass: a better long-term strategy. Surg Obes Relat Dis. 2015;11:1280-1.
• Andrea GI, Ana BC. Obesity-related epigenetic changes after bariatric surgery. Front Endocrinol. 2019;10:232.
• González MM, Gracia MMN, Lourdes GS, Eduardo GF, Francisco T, Sonsoles M. Decreased blood pressure is related to changes in NF-kB promoter methylation levels after bariatric surgery. Surg Obes Relat Dis. 2018;14:1327-34.
• Assem S, Abdelbaki TN, Mohy-E Dine SH, Ketat AF, Abdelmonsif DA. Serpine-1 gene methylation and protein as molecular predictors of laparoscopic sleeve gastrectomy outcome. Obes Surg. 2020;30:2620–30.
• Beisani M, Pappa S, Moreno P, Martínez E, Tarasco J, Granada ML et al. Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cell. Clin Nutr. 2020;39:592-98.
• He L, Li J, Wang X, Ying Y, Xie H, Yan H et al. The dual role of N6-methyladenosine modification of RNAs is involved in human cancers. J Cell Mol Med. 2018;22:4630–9.
• Batista PJ. The RNA modification N (6)-methyladenosine and Its implications in human disease. Genomics Proteomics Bioinform. 2017;15:154–63.
• Xie B, Deng Z, Pan Y, Fu C, Fan S, Tao Y. Post-transcriptional regulation DPC4 gene by miR-190 in colorectal cancer cells. J Cancer Res Ther. 2018;14:838–43.
• Li J, Meng S, Xu M, Wang S, He L, Xu X et al. Downregulation of N (6)-methyladenosine binding YTHDF2 protein mediated by miR-493-3p suppresses prostate cancer by elevating N (6)-methyladenosine levels. Oncotarget. 2018;9:3752–64.
• Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ et al. Mammalian WTAP is a regulatory subunit of the RNA N6- methyladenosine methyltransferase. Cell Res. 2014;24:177-89.
• Xu L, Pan J, Pan H. Construction and validation of an m6A RNA methylation regulators based prognostic signature for esophageal cancer. Cancer Manag Res. 2020;12:5385–94.
• Xia TL, Yan SM, Yuan L, Zeng MS. Upregulation of METTL3 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Manag Res. 2020;12:5729–37.
• Sang L, Sun L, Wang A, Zhang H, Yuan Y. The N6-Methyladenosine features of mRNA and aberrant expression of m6A modified genes in gastric cancer and their potential impact on the risk and prognosis. Front Genet. 2020;11:561-66.
• Shen X, Zhao K, Xu L, Cheng G, Zhu J, Gan L et al. YTHDF2 Inhibits gastric cancer cell growth by regulating FOXC2 signaling pathway. Front Genet. 2021;11:592042.
• Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ et al. YTHDF3 facilitates translation and decay of N (6)-methyladenosine-modified RNA. Cell Res. 2017;27:315–28.
• Zhao Q, Zhao Y, Hu W, Zhang Y, Wu X, Lu J et al. m6A RNA modification modulates PI3K/Akt/mTOR signal pathway gastrointestinal cancer. Theranostics. 2020;10:9528-43.
• Cohen J. Statistical power analysis for the behavioral sciences. New York, NY: Routledge Academic, 1988.
• Taylor MA, Szczerbinski L, Citko A, Niemira M, Gorska M, Hady HR et al. Sex-specific glucose homeostasis and anthropometric responses to sleeve gastrectomy in obese patients. Nutrients. 2019;11:2408.
• Dilimulati D, Cai M, Lin Z, Zhang Y, Du L, Zhou D et al. Correlation between sex hormones and non alcoholic fatty liver disease before and after laparoscopic sleeve gastrectomy. Obesity Surgery. 2021;31:4901–10.
• Gu L, Lin K, Du N, Minyao D, Lou D, Chen P. Differences in the effects of laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass on gut hormones: systematic and meta-analysis. Surg Obes Relat Dis. 2021;17:444-55.
• Thomas RM, Jirapinyo P, Thompson CC. Effect of sleeve gastrectomy on ghrelin, GLP-1, PYY, and GIP gut hormones. Ann Surg. 2020;272:72-80.
• Mackenzie H, Markar SR, Askari A, Faiz O, Hull M, Purkayastha S. et al. Obesity surgery and risk of cancer. Br J Surg. 2018;105:1650–1657.
• Aravani A, Downing A, Thomas JD, Lagergren J, Morris EJA, Hull MA. Obesity surgery and risk of colorectal and other obesity-related cancers: An English population-based cohort study. Cancer Epidemiol. 2018;53:99–104.
• Benvenga R, Roussel J, Cohen R, Bouchoucha M, Bendacha Y, Catheline JM. Long-term endoscopic follow-up after sleeve gastrectomy. J Visc Surg. 2022;159:39-42.
• Shi B, Liu W, Yang K, Jiang G, Wang H. The role, mechanism, and application of rna methyltransferase mettl14 in gastrointestinal cancer. Mol Cancer. 2022;21:163.
• Hu J, Lin H, Wang W, Su Q, Cao B. Mettl14‑mediated rna methylation in digestive system tumors. Int J Mol Med. 2023;52:86.
• Chen X, Xu M, Xu X, Zeng K, Liu X, Sun L et al. METTL14 suppresses CRC progression via regulating N6-methyladenosine-dependent primary miR-375 processing. Mol Ther. 2020;28:599–612.
• Chen X, Xu M, Xu X, Zeng K, Liu X, Pan B, et al. METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer. Mol Cancer. 2020;19:106.
• Wang S, Gan M, Chen C, Zhang Y, Kong J, Zhang H et al. Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N(6)-methyladenosine methylation through methyltransferase-like 14. Cancer Sci. 2021;112:3243–54.
• Liu X, Xiao M, Zhang L, Li L, Zhu G, Shen E et al. The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021;35:e23655.
• Zhang C, Zhang M, Ge S, Huang W, Lin X, Gao J et al. Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K-Akt signaling in gastric cancer. Cancer Med. 2019;8:4766–81.
• Wang H, Wei W, Zhang ZY, Liu Y, Shi B, Zhong W et al. TCF4 and HuR mediated-METTL14 suppresses dissemination of colorectal cancer via N6-methyladenosine-dependent silencing of ARRDC4. Cell Death Dis. 2021;13:3.
• Fan HN, Chen ZY, Chen XY, Chen M, Yi YC, Zhu JS et al. METTL14-mediated m(6)A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis. Mol Cancer. 2022;21:51.
• Sorci M, Ianniello Z, Cruciani S, Larivera S, Ginistrelli LC, Capuano E et al. METTL3 regulates WTAP protein homeostasis. Cell Death Dis. 2018;9:796.