J Korean Med Sci.  2022 Jul;37(28):e220. 10.3346/jkms.2022.37.e220.

Establishment of Patient-Derived Gastric Cancer Organoid Model From Tissue Obtained by Endoscopic Biopsies

• Song H
• Park JY
• Kim JH
• Shin TS
• Hong SA
• Huda MN
• Kim BJ
• Kim JG

• KMID: 2531802
• DOI: http://doi.org/10.3346/jkms.2022.37.e220

Abstract

Cancer organoids are three-dimensional mini-organ analogues derived from cancer tissues and have been proposed as models capable of simulating the structure and function of human organs and tissues in vitro. We sought to establish gastric cancer patient-derived organoids (PDOs) from tissues obtained by endoscopic biopsies. Gastric cancer-PDOs were successfully established and cultured from cancer tissues with gastric adenocarcinoma by endoscopic biopsies. To confirm that gastric cancer-PDOs were derived from cancer tissue, the consistency of the original cancer tissue was assessed by histopathological examination. As a result, it was confirmed that the shape and internal structure of gastric cancer-PDO were derived from the original gastric cancer cells, and the tumor specificity of gastric cancerPDO was confirmed through Periodic acid-Schiff (PAS) and polyclonal carcinoembryonic antigen antibody staining. These results demonstrate that gastric cancer-PDO models show the characteristics of primary tumors and have potential for drug screening and providing a personalized medicine platform.

Keyword

Gastric Cancer; Organoid; Endoscopy; Biopsy; Precision Medicine

Figure

• 

  Fig. 1 Schematic diagram of preparation, cultivation and isolation of gastric organoids. (A) The method for generating organoids from endoscopic biopsy. (B) Manual selection procedure to isolate single gastric cancer organoids (pure phenotype) based on morphology from cancer organoid cluster (mixed phenotype).

• 

  Fig. 2 Microscopic images of PDOs before and after staining. (A) Unstained PDOs before (top left; generated from normal tissue, top right; generated from cancer tissue, original magnification, ×40) and after manual selection (bottom left; PDO single cell, bottom right; multiple PDOs). (B) Comparative histological and IHC images of the biopsy specimens and pure gastric cancer-PDOs. On H&E stain, histologic features of the gastric cancer-PDO (top left; original magnification, ×400) are similar to those of original tumor tissue from the patient (top right; original magnification, ×100). The intraluminal mucin from gastric cancer-PDO (middle left; original magnification, ×200) and original tumor tissue (middle right; original magnification, ×400) is highlighted by PAS staining. CEA expression as apicoluminal pattern is the same in gastric PDO (bottom left; original magnification, ×200) and original tumor tissue (bottom right; original magnification, ×400).PDO = patient-derived organoid, IHC = immunohistochemistry, H&E = hematoxylin and eosin, PAS = Periodic acid-Schiff, CEA = carcinoembryonic antigen.

Reference

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancer in 185 countries. CA Cancer J Clin. 2021; 71(3):209–249. PMID: 33538338.

2. Guideline Committee of the Korean Gastric Cancer Association (KGCA), Development Working Group & Review Panel. Korean practice guideline for gastric cancer 2018: an evidence-based, multi-disciplinary approach. J Gastric Cancer. 2019; 19(1):1–48. PMID: 30944757.

3. Jeon J, Cheong JH. Clinical implementation of precision medicine in gastric cancer. J Gastric Cancer. 2019; 19(3):235–253. PMID: 31598369.

4. Aboulkheyr Es H, Montazeri L, Aref AR, Vosough M, Baharvand H. Personalized cancer medicine: an organoid approach. Trends Biotechnol. 2018; 36(4):358–371. PMID: 29366522.

5. Seidlitz T, Merker SR, Rothe A, Zakrzewski F, von Neubeck C, Grützmann K, et al. Human gastric cancer modelling using organoids. Gut. 2019; 68(2):207–217. PMID: 29703791.

6. Yan HH, Siu HC, Law S, Ho SL, Yue SS, Tsui WY, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell. 2018; 23(6):882–897.e11. PMID: 30344100.

7. Steele NG, Chakrabarti J, Wang J, Biesiada J, Holokai L, Chang J, et al. An organoid-based preclinical model of human gastric cancer. Cell Mol Gastroenterol Hepatol. 2019; 7(1):161–184. PMID: 30522949.

8. Wallaschek N, Niklas C, Pompaiah M, Wiegering A, Germer CT, Kircher S, et al. Establishing pure cancer organoid cultures: identification, selection and verification of cancer phenotypes and genotypes. J Mol Biol. 2019; 431(15):2884–2893. PMID: 31150736.

9. Nam SY, Lee SJ, Lim HJ, Park JY, Jeon SW. Clinical risk factors and pattern of initial fungal contamination in endoscopic biopsy-derived gastrointestinal cancer organoid culture. Korean J Intern Med. 2021; 36(4):878–887. PMID: 33826841.