BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
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VSTM2L is a promising therapeutic target and a prognostic soluble-biomarker in cholangiocarcinoma

  • Jungwhoi Lee (Department of Applied Life Science, Jeju National University) ;
  • Woogwang Sim (Department of Anatomy, University of California San Francisco) ;
  • Jungsul Lee (Department of Bio and Brain Engineering, KAIST) ;
  • Jae-Hoon Kim (Department of Applied Life Science, Jeju National University)
  • 투고 : 2023.10.25
  • 심사 : 2024.01.12
  • 발행 : 2024.07.31
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초록

The aim of the present study is to provide a rational background for silencing the V-set and transmembrane domain containing 2 like (VSTM2L) in consort with recognising soluble VSTM2L against cholangiocarcinoma. A therapeutic target against cholangiocarcinoma was selected using iterative patient partitioning (IPP) calculation, and it was verified by in vitro and in silico analyses. VSTM2L was selected as a potential therapeutic target against cholangiocarcinoma. Silencing the VSTM2L expression significantly attenuated the viability and survival of cholangiocarcinoma cells through blockade of the intracellular signalling pathway. In silico analysis showed that VSTM2L affected the positive regulation of cell growth in cholangiocarcinoma. Liptak's z value revealed that the expression of VSTM2L worsened the prognosis of cholangiocarcinoma patients. In addition, soluble VSTM2L was significantly detected in the whole blood of cholangiocarcinoma patients compared with that of healthy donors. Our report reveals that VSTM2L might be the potential therapeutic target and a soluble prognostic biomarker against cholangiocarcinoma.

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과제정보

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1A6A1A03012862 and 2021R1I1A1A01041462).

참고문헌

  1. Khan SA, Thomas HC, Davidson BR and Taylor-Robinson SD (2005) Cholangiocarcinoma. Lancet 366, 1303-1314 
  2. Bragazzi MC, Ridola L, Safarikia S et al (2018) New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin. Ann Gastroenterol 31, 42-55 
  3. Patel T (2001) Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33, 1353-1357 
  4. Malhi H and Gores GJ (2006) Cholangiocarcinoma: modern advances in understanding a deadly old disease. J Hepatol 45, 856-867 
  5. Khan SA, Emadossadaty S, Ladep NG et al (2012) Rising trends in cholangiocarcinoma: is the ICD classification system misleading us? J Hepatol 56, 848-854 
  6. Zhang S, Xiong H, Yang J and Yuan X (2021) Pan-cancer analysis reveals the multidimensional expression and prognostic and immunologic roles of VSTM2L in cancer. Front Mol Biosci 8, 792154 
  7. Rossini L, Hashimoto Y, Suzuki H et al (2011) VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin. FASEB J 25, 1983-2000 
  8. Liu H, Zhang Z, Zhen P and Zhou M (2021) High expression of VSTM2L induced resistance to chemoradiotherapy in rectal cancer through downstream IL-4 signaling. J Immunol Res 2021, 6657012 
  9. Li Y, Zhang J, Cai Y et al (2023) VSTM2L contributes to anoikis resistance and acts as a novel biomarker for metastasis and clinical outcome in ovarian cancer. Biochem Biophys Res Commun 658, 107-115 
  10. Banales JM, Marin JJG, Lamarca A et al (2020) Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol 17, 557-588 
  11. Zhu J, Chen X, Liao Z, He C and Hu X (2015) TGFBI protein high expression predicts poor prognosis in colorectal cancer patients. Int J Clin Exp Pathol 8, 702-710 
  12. Pajares MJ, Agorreta J, Salvo E et al (2014) TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients. Br J Cancer 110, 1545-1551 
  13. Macias RIR, Banales JM, Sangro B et al (2018) The search for novel diagnostic and prognostic biomarkers in cholangiocarcinoma. Biochim Biophys Acta Mol Basis Dis 1864, 1468-1477 
  14. Miwa M, You G, Tanaka H et al (2014) Analysis of new biomarkers for cholangiocarcinoma. J Hepatobiliary Pancreat Sci 21, 397-398 
  15. Sim W, Lee J and Choi C (2017) Robust method for identification of prognostic gene signatures from gene expression profiles. Sci Rep 7, 16926 
  16. Lee J, Lee J, Sim W and Kim JH (2022) Soluble TGFBI aggravates the malignancy of cholangiocarcinoma through activation of the ITGB1 dependent PPARgamma signalling pathway. Cell Oncol (Dordr) 45, 275-291 
  17. Lee J, Kim E, Chong K et al (2022) Atypical induction of HIF-1alpha expression by pericellular Notch1 signaling suffices for the malignancy of glioblastoma multiforme cells. Cell Mol Life Sci 79, 537 
  18. Lee J, Chong K, Lee J et al (2022) Differential dependency of human glioblastoma cells on vascular endothelial growth factor‑A signaling via neuropilin‑1. Int J Oncol 61, 122 
  19. Lee J, Lee J, Yu H, Choi K and Choi C (2011) Differential dependency of human cancer cells on vascular endothelial growth factor-mediated autocrine growth and survival. Cancer Lett 309, 145-150