- 1. The First Clinical College of Medicine, Lanzhou University, Lanzhou 730000, P. R. China;
- 2. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China;
Citation: PENG Lei, ZHU Kexiang. Research progress of organoid model in pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(7): 863-869. doi: 10.7507/1007-9424.202302021 Copy
1. | Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33. |
2. | Zarei M, Hajihassani O, Hue JJ, et al. Targeting wild-type IDH1 enhances chemosensitivity in pancreatic cancer. bioRxiv, 2023: 2023.03.29.534596. doi: 10.1101/2023.03.29.534596. |
3. | Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30. |
4. | Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pan-creas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921. |
5. | 尹周一, 王梦圆, 游伟程, 等. 2022美国癌症统计报告解读及中美癌症流行情况对比. 肿瘤综合治疗电子杂志, 2022, 8(2): 54-63. |
6. | 周永杰, 石毓君. 类器官研究进展及展望. 中国普外基础与临床杂志, 2022, 29(6): 716-718. |
7. | 李程, 陈拥华, 麦刚, 等. 精准医疗时代胰腺癌个体化类器官研究现状与应用前景. 中国普外基础与临床杂志, 2016, 23(10): 1272-1275. |
8. | Unger FT, Witte I, David KA. Prediction of individual response to anticancer therapy: historical and future perspectives. Cell Mol Life Sci, 2015, 72(4): 729-757. |
9. | Melzer MK, Roger E, Kleger A. State-matched organoid models to fight pancreatic cancer. Trends Cancer, 2022, 8(6): 445-447. |
10. | Cantrell MA, Kuo CJ. Organoid modeling for cancer precision medicine. Genome Med, 2015, 7(1): 32. doi: 10.1186/s13073-015-0158-y. |
11. | Zhang HC, Kuo CJ. Personalizing pancreatic cancer organoids with hPSCs. Nat Med, 2015, 21(11): 1249-1251. |
12. | Below CR, Kelly J, Brown A, et al. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater, 2022, 21(1): 110-119. |
13. | Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell, 2015, 160(1-2): 324-338. |
14. | Georgakopoulos N, Prior N, Angres B, et al. Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids. BMC Dev Biol, 2020, 20(1): 4. doi: 10.1186/s12861-020-0209-5. |
15. | Watanabe S, Yogo A, Otsubo T, et al. Establishment of patient-derived organoids and a characterization-based drug discovery platform for treatment of pancreatic cancer. BMC Cancer, 2022, 22(1): 489. doi: 10.1186/s12885-022-09619-9. |
16. | Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci. harvard. edu. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell, 2017, 32(2): 185-203. e13. doi: 10.1016/j.ccell.2017.07.007. |
17. | Koga Y, Ochiai A. Systematic review of patient-derived xenograft models for preclinical studies of anti-cancer drugs in solid tumors. Cells, 2019, 8(5): 418. doi: 10.1186/s12885-022-09619-9. |
18. | Kokkinos J, Sharbeen G, Haghighi KS, et al. Ex vivo culture of intact human patient derived pancreatic tumour tissue. Sci Rep, 2021, 11(1): 1944. doi: 10.1038/s41598-021-81299-0. |
19. | Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer, 2018, 18(7): 407-418. |
20. | Ooft SN, Weeber F, Dijkstra KK, et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci Transl Med, 2019, 11(513): eaay2574. doi: 10.1126/scitranslmed.aay2574. |
21. | Driehuis E, Gracanin A, Vries RGJ, et al. Establishment of pancreatic organoids from normal tissue and tumors. STAR Protoc, 2020, 1(3): 100192. doi: 10.1016/j.xpro.2020.100192. |
22. | Tiriac H, Bucobo JC, Tzimas D, et al. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment. Gastrointest Endosc, 2018, 87(6): 1474-1480. |
23. | Seppälä TT, Zimmerman JW, Sereni E, et al. Patient-derived organoid pharmacotyping is a clinically tractable strategy for precision medicine in pancreatic cancer. Ann Surg, 2020, 272(3): 427-435. |
24. | Dantes Z, Yen HY, Pfarr N, et al. Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology. JCI Insight, 2020, 5(15): e137809. doi: 10.1172/jci.insight.137809. |
25. | Jain D, Allen TC, Aisner DL, et al. Rapid on-site evaluation of endobronchial ultrasound-guided transbronchial needle aspirations for the diagnosis of lung cancer: a perspective from members of the Pulmonary Pathology Society. Arch Pathol Lab Med, 2018, 142(2): 253-262. |
26. | Conrad R, Yang SE, Chang S, et al. Comparison of cytopathologist-performed ultrasound-guided fine-needle aspiration with cytopathologist-performed palpation-guided fine-needle aspiration: a single institutional experience. Arch Pathol Lab Med, 2018, 142(10): 1260-1267. |
27. | Boyd JD, Smith GD, Hong H, et al. Fine-needle aspiration is superior to needle core biopsy as a sample acquisition method for flow cytometric analysis in suspected hematologic neoplasms. Cytometry B Clin Cytom, 2015, 88(1): 64-68. |
28. | Yane K, Kuwatani M, Yoshida M, et al. Non-negligible rate of needle tract seeding after endoscopic ultrasound-guided fine-needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer. Dig Endosc, 2020, 32(5): 801-811. |
29. | Kanno A, Yasuda I, Irisawa A, et al. Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: multicenter retrospective study. Dig Endosc, 2021, 33(7): 1146-1157. |
30. | Romero-Calvo I, Weber CR, Ray M, et al. Human organoids share structural and genetic features with primary pancreatic adenocarcinoma tumors. Mol Cancer Res, 2019, 17(1): 70-83. |
31. | Wiedenmann S, Breunig M, Merkle J, et al. Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip. Nat Biomed Eng, 2021, 5(8): 897-913. |
32. | Bragança J, Lopes JA, Mendes-Silva L, et al. Induced pluripotent stem cells, a giant leap for mankind therapeutic applications. World J Stem Cells, 2019, 11(7): 421-430. |
33. | Hirshorn ST, Steele N, Zavros Y. Modeling pancreatic pathophysiology using genome editing of adult stem cell-derived and induced pluripotent stem cell (iPSC)-derived organoids. Am J Physiol Gastrointest Liver Physiol, 2021, 320(6): G1142-G1150. doi: 10.1152/ajpgi.00329.2020. |
34. | Neal JT, Li X, Zhu J, et al. Organoid modeling of the tumor immune microenvironment. Cell, 2018, 175(7): 1972-1988. |
35. | Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature, 2013, 501(7467): 346-354. |
36. | Huang L, Desai R, Conrad DN, et al. Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids. Cell Stem Cell, 2021, 28(6): 1090-1104. |
37. | Breunig M, Merkle J, Wagner M, et al. Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells. Cell Stem Cell, 2021, 28(6): 1105-1124. |
38. | Dedhia PH, Bertaux-Skeirik N, Zavros Y, et al. Organoid models of human gastrointestinal development and disease. Gastroenterology, 2016, 150(5): 1098-1112. |
39. | Orth M, Metzger P, Gerum S, et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol, 2019, 14(1): 141. doi: 10.1186/s13014-019-1345-6. |
40. | Gao H, Chakraborty G, Zhang Z, et al. Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling. Cell, 2016, 166(1): 47-62. |
41. | An T, Qin S, Xu Y, et al. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles, 2015, 4: 27522. doi: 10.3402/jev.v4.27522. |
42. | Roma-Rodrigues C, Fernandes AR, Baptista PV. Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells. Biomed Res Int, 2014, 2014: 179486. doi: 10.1155/2014/179486. |
43. | Xu H, Lyu X, Yi M, et al. Organoid technology and applications in cancer research. J Hematol Oncol, 2018, 11(1): 116. doi: 10.1186/s13045-018-0662-9. |
44. | Yang J, Zhang Z, Zhang Y, et al. ZIP4 promotes muscle wasting and cachexia in mice with orthotopic pancreatic tumors by stimulating RAB27B-regulated release of extracellular vesicles from cancer cells. Gastroenterology, 2019, 156(3): 722-734. |
45. | Szvicsek Z, Oszvald Á, Szabó L, et al. Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors. Cell Mol Life Sci, 2019, 76(12): 2463-2476. |
46. | Zhou J, Flores-Bellver M, Pan J, et al. Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells. Sci Rep, 2021, 11(1): 21128. doi: 10.1038/s41598-021-00542-w. |
47. | Zeöld A, Sándor GO, Kiss A, et al. Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology. Cell Mol Life Sci, 2021, 78(6): 3005-3020. |
48. | Frampton AE, Prado MM, López-Jiménez E, et al. Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden. Oncotarget, 2018, 9(27): 19006-19013. |
49. | Leca J, Martinez S, Lac S, et al. Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J Clin Invest, 2016, 126(11): 4140-4156. |
50. | Allenson K, Castillo J, San Lucas FA, et al. High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. Ann Oncol, 2017, 28(4): 741-747. |
51. | Yang Z, Zhao N, Cui J, et al. Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210. Cell Oncol (Dordr), 2020, 43(1): 123-136. |
52. | Yemelyanova A, Vang R, Kshirsagar M, et al. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol, 2011, 24(9): 1248-1253. |
53. | Boogerd LSF, Vuijk FA, Hoogstins CES, et al. Correlation between preoperative serum carcinoembryonic antigen levels and expression on pancreatic and rectal cancer tissue. Biomark Cancer, 2017, 9: 1179299X17710016. doi: 10.1177/1179299X17710016. |
54. | Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol, 2000, 13(9): 962-972. |
55. | Li B, Wang Y, Wang J, et al. Negative p53 expression confers worse prognosis in patients with resected pancreatic ductal adeno-carcinoma: research focused on reinterpretation of immuno-histochemical staining. Pancreas, 2022, 51(9): 1217-1224. |
56. | Neesse A, Hahnenkamp A, Griesmann H, et al. Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. Gut, 2013, 62(7): 1034-1043. |
57. | Zapata M, Cohen C, Siddiqui MT. Immunohistochemical expression of SMAD4, CK19, and CA19-9 in fine needle aspiration samples of pancreatic adenocarcinoma: utility and potential role. Cytojournal, 2007, 4: 13. doi: 10.1186/1742-6413-4-13. |
58. | Kadri S, Long BC, Mujacic I, et al. Clinical validation of a next-generation sequencing genomic oncology panel via cross-platform benchmarking against established amplicon sequencing assays. J Mol Diagn, 2017, 19(1): 43-56. |
59. | Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 2016, 531(7592): 47-52. |
60. | Biankin AV, Waddell N, Kassahn KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature, 2012, 491(7424): 399-405. |
61. | Sinn M, Striefler JK, Sinn BV, et al. Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study. J Surg Oncol, 2013, 108(6): 398-402. |
62. | Shiihara M, Ishikawa T, Saiki Y, et al. Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers. Eur J Cancer, 2021, 148: 239-250. |
63. | Beutel AK, Schütte L, Scheible J, et al. A prospective feasibility trial to challenge patient-derived pancreatic cancer organoids in predicting treatment response. Cancers (Basel), 2021, 13(11): 2539. doi: 10.3390/cancers13112539. |
64. | Schuster B, Junkin M, Kashaf SS, et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat Commun, 2020, 11(1): 5271. doi: 10.1038/s41467-020-19058-4. |
65. | Grossman JE, Muthuswamy L, Huang L, et al. Organoid sensitivity correlates with therapeutic response in patients with pancreatic cancer. Clin Cancer Res, 2022, 28(4): 708-718. |
66. | Huang L, Holtzinger A, Jagan I, et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med, 2015, 21(11): 1364-1371. |
- 1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
- 2. Zarei M, Hajihassani O, Hue JJ, et al. Targeting wild-type IDH1 enhances chemosensitivity in pancreatic cancer. bioRxiv, 2023: 2023.03.29.534596. doi: 10.1101/2023.03.29.534596.
- 3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin, 2017, 67(1): 7-30.
- 4. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pan-creas cancers in the United States. Cancer Res, 2014, 74(11): 2913-2921.
- 5. 尹周一, 王梦圆, 游伟程, 等. 2022美国癌症统计报告解读及中美癌症流行情况对比. 肿瘤综合治疗电子杂志, 2022, 8(2): 54-63.
- 6. 周永杰, 石毓君. 类器官研究进展及展望. 中国普外基础与临床杂志, 2022, 29(6): 716-718.
- 7. 李程, 陈拥华, 麦刚, 等. 精准医疗时代胰腺癌个体化类器官研究现状与应用前景. 中国普外基础与临床杂志, 2016, 23(10): 1272-1275.
- 8. Unger FT, Witte I, David KA. Prediction of individual response to anticancer therapy: historical and future perspectives. Cell Mol Life Sci, 2015, 72(4): 729-757.
- 9. Melzer MK, Roger E, Kleger A. State-matched organoid models to fight pancreatic cancer. Trends Cancer, 2022, 8(6): 445-447.
- 10. Cantrell MA, Kuo CJ. Organoid modeling for cancer precision medicine. Genome Med, 2015, 7(1): 32. doi: 10.1186/s13073-015-0158-y.
- 11. Zhang HC, Kuo CJ. Personalizing pancreatic cancer organoids with hPSCs. Nat Med, 2015, 21(11): 1249-1251.
- 12. Below CR, Kelly J, Brown A, et al. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater, 2022, 21(1): 110-119.
- 13. Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell, 2015, 160(1-2): 324-338.
- 14. Georgakopoulos N, Prior N, Angres B, et al. Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids. BMC Dev Biol, 2020, 20(1): 4. doi: 10.1186/s12861-020-0209-5.
- 15. Watanabe S, Yogo A, Otsubo T, et al. Establishment of patient-derived organoids and a characterization-based drug discovery platform for treatment of pancreatic cancer. BMC Cancer, 2022, 22(1): 489. doi: 10.1186/s12885-022-09619-9.
- 16. Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci. harvard. edu. Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell, 2017, 32(2): 185-203. e13. doi: 10.1016/j.ccell.2017.07.007.
- 17. Koga Y, Ochiai A. Systematic review of patient-derived xenograft models for preclinical studies of anti-cancer drugs in solid tumors. Cells, 2019, 8(5): 418. doi: 10.1186/s12885-022-09619-9.
- 18. Kokkinos J, Sharbeen G, Haghighi KS, et al. Ex vivo culture of intact human patient derived pancreatic tumour tissue. Sci Rep, 2021, 11(1): 1944. doi: 10.1038/s41598-021-81299-0.
- 19. Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer, 2018, 18(7): 407-418.
- 20. Ooft SN, Weeber F, Dijkstra KK, et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients. Sci Transl Med, 2019, 11(513): eaay2574. doi: 10.1126/scitranslmed.aay2574.
- 21. Driehuis E, Gracanin A, Vries RGJ, et al. Establishment of pancreatic organoids from normal tissue and tumors. STAR Protoc, 2020, 1(3): 100192. doi: 10.1016/j.xpro.2020.100192.
- 22. Tiriac H, Bucobo JC, Tzimas D, et al. Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment. Gastrointest Endosc, 2018, 87(6): 1474-1480.
- 23. Seppälä TT, Zimmerman JW, Sereni E, et al. Patient-derived organoid pharmacotyping is a clinically tractable strategy for precision medicine in pancreatic cancer. Ann Surg, 2020, 272(3): 427-435.
- 24. Dantes Z, Yen HY, Pfarr N, et al. Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology. JCI Insight, 2020, 5(15): e137809. doi: 10.1172/jci.insight.137809.
- 25. Jain D, Allen TC, Aisner DL, et al. Rapid on-site evaluation of endobronchial ultrasound-guided transbronchial needle aspirations for the diagnosis of lung cancer: a perspective from members of the Pulmonary Pathology Society. Arch Pathol Lab Med, 2018, 142(2): 253-262.
- 26. Conrad R, Yang SE, Chang S, et al. Comparison of cytopathologist-performed ultrasound-guided fine-needle aspiration with cytopathologist-performed palpation-guided fine-needle aspiration: a single institutional experience. Arch Pathol Lab Med, 2018, 142(10): 1260-1267.
- 27. Boyd JD, Smith GD, Hong H, et al. Fine-needle aspiration is superior to needle core biopsy as a sample acquisition method for flow cytometric analysis in suspected hematologic neoplasms. Cytometry B Clin Cytom, 2015, 88(1): 64-68.
- 28. Yane K, Kuwatani M, Yoshida M, et al. Non-negligible rate of needle tract seeding after endoscopic ultrasound-guided fine-needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer. Dig Endosc, 2020, 32(5): 801-811.
- 29. Kanno A, Yasuda I, Irisawa A, et al. Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: multicenter retrospective study. Dig Endosc, 2021, 33(7): 1146-1157.
- 30. Romero-Calvo I, Weber CR, Ray M, et al. Human organoids share structural and genetic features with primary pancreatic adenocarcinoma tumors. Mol Cancer Res, 2019, 17(1): 70-83.
- 31. Wiedenmann S, Breunig M, Merkle J, et al. Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip. Nat Biomed Eng, 2021, 5(8): 897-913.
- 32. Bragança J, Lopes JA, Mendes-Silva L, et al. Induced pluripotent stem cells, a giant leap for mankind therapeutic applications. World J Stem Cells, 2019, 11(7): 421-430.
- 33. Hirshorn ST, Steele N, Zavros Y. Modeling pancreatic pathophysiology using genome editing of adult stem cell-derived and induced pluripotent stem cell (iPSC)-derived organoids. Am J Physiol Gastrointest Liver Physiol, 2021, 320(6): G1142-G1150. doi: 10.1152/ajpgi.00329.2020.
- 34. Neal JT, Li X, Zhu J, et al. Organoid modeling of the tumor immune microenvironment. Cell, 2018, 175(7): 1972-1988.
- 35. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature, 2013, 501(7467): 346-354.
- 36. Huang L, Desai R, Conrad DN, et al. Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids. Cell Stem Cell, 2021, 28(6): 1090-1104.
- 37. Breunig M, Merkle J, Wagner M, et al. Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells. Cell Stem Cell, 2021, 28(6): 1105-1124.
- 38. Dedhia PH, Bertaux-Skeirik N, Zavros Y, et al. Organoid models of human gastrointestinal development and disease. Gastroenterology, 2016, 150(5): 1098-1112.
- 39. Orth M, Metzger P, Gerum S, et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol, 2019, 14(1): 141. doi: 10.1186/s13014-019-1345-6.
- 40. Gao H, Chakraborty G, Zhang Z, et al. Multi-organ site metastatic reactivation mediated by non-canonical discoidin domain receptor 1 signaling. Cell, 2016, 166(1): 47-62.
- 41. An T, Qin S, Xu Y, et al. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J Extracell Vesicles, 2015, 4: 27522. doi: 10.3402/jev.v4.27522.
- 42. Roma-Rodrigues C, Fernandes AR, Baptista PV. Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells. Biomed Res Int, 2014, 2014: 179486. doi: 10.1155/2014/179486.
- 43. Xu H, Lyu X, Yi M, et al. Organoid technology and applications in cancer research. J Hematol Oncol, 2018, 11(1): 116. doi: 10.1186/s13045-018-0662-9.
- 44. Yang J, Zhang Z, Zhang Y, et al. ZIP4 promotes muscle wasting and cachexia in mice with orthotopic pancreatic tumors by stimulating RAB27B-regulated release of extracellular vesicles from cancer cells. Gastroenterology, 2019, 156(3): 722-734.
- 45. Szvicsek Z, Oszvald Á, Szabó L, et al. Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors. Cell Mol Life Sci, 2019, 76(12): 2463-2476.
- 46. Zhou J, Flores-Bellver M, Pan J, et al. Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells. Sci Rep, 2021, 11(1): 21128. doi: 10.1038/s41598-021-00542-w.
- 47. Zeöld A, Sándor GO, Kiss A, et al. Shared extracellular vesicle miRNA profiles of matched ductal pancreatic adenocarcinoma organoids and blood plasma samples show the power of organoid technology. Cell Mol Life Sci, 2021, 78(6): 3005-3020.
- 48. Frampton AE, Prado MM, López-Jiménez E, et al. Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden. Oncotarget, 2018, 9(27): 19006-19013.
- 49. Leca J, Martinez S, Lac S, et al. Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J Clin Invest, 2016, 126(11): 4140-4156.
- 50. Allenson K, Castillo J, San Lucas FA, et al. High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. Ann Oncol, 2017, 28(4): 741-747.
- 51. Yang Z, Zhao N, Cui J, et al. Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210. Cell Oncol (Dordr), 2020, 43(1): 123-136.
- 52. Yemelyanova A, Vang R, Kshirsagar M, et al. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod Pathol, 2011, 24(9): 1248-1253.
- 53. Boogerd LSF, Vuijk FA, Hoogstins CES, et al. Correlation between preoperative serum carcinoembryonic antigen levels and expression on pancreatic and rectal cancer tissue. Biomark Cancer, 2017, 9: 1179299X17710016. doi: 10.1177/1179299X17710016.
- 54. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol, 2000, 13(9): 962-972.
- 55. Li B, Wang Y, Wang J, et al. Negative p53 expression confers worse prognosis in patients with resected pancreatic ductal adeno-carcinoma: research focused on reinterpretation of immuno-histochemical staining. Pancreas, 2022, 51(9): 1217-1224.
- 56. Neesse A, Hahnenkamp A, Griesmann H, et al. Claudin-4-targeted optical imaging detects pancreatic cancer and its precursor lesions. Gut, 2013, 62(7): 1034-1043.
- 57. Zapata M, Cohen C, Siddiqui MT. Immunohistochemical expression of SMAD4, CK19, and CA19-9 in fine needle aspiration samples of pancreatic adenocarcinoma: utility and potential role. Cytojournal, 2007, 4: 13. doi: 10.1186/1742-6413-4-13.
- 58. Kadri S, Long BC, Mujacic I, et al. Clinical validation of a next-generation sequencing genomic oncology panel via cross-platform benchmarking against established amplicon sequencing assays. J Mol Diagn, 2017, 19(1): 43-56.
- 59. Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 2016, 531(7592): 47-52.
- 60. Biankin AV, Waddell N, Kassahn KS, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature, 2012, 491(7424): 399-405.
- 61. Sinn M, Striefler JK, Sinn BV, et al. Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study. J Surg Oncol, 2013, 108(6): 398-402.
- 62. Shiihara M, Ishikawa T, Saiki Y, et al. Development of a system combining comprehensive genotyping and organoid cultures for identifying and testing genotype-oriented personalised medicine for pancreatobiliary cancers. Eur J Cancer, 2021, 148: 239-250.
- 63. Beutel AK, Schütte L, Scheible J, et al. A prospective feasibility trial to challenge patient-derived pancreatic cancer organoids in predicting treatment response. Cancers (Basel), 2021, 13(11): 2539. doi: 10.3390/cancers13112539.
- 64. Schuster B, Junkin M, Kashaf SS, et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nat Commun, 2020, 11(1): 5271. doi: 10.1038/s41467-020-19058-4.
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