High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer


Autoři: Ryotaro Ohkuma aff001;  Erica Yada aff004;  Shumpei Ishikawa aff005;  Daisuke Komura aff005;  Hidenobu Ishizaki aff006;  Koji Tamada aff007;  Yutaro Kubota aff002;  Kazuyuki Hamada aff002;  Hiroo Ishida aff002;  Yuya Hirasawa aff002;  Hirotsugu Ariizumi aff002;  Etsuko Satoh aff002;  Midori Shida aff001;  Makoto Watanabe aff001;  Rie Onoue aff001;  Kiyohiro Ando aff001;  Junji Tsurutani aff002;  Kiyoshi Yoshimura aff002;  Takehiko Yokobori aff011;  Tetsuro Sasada aff004;  Takeshi Aoki aff012;  Masahiko Murakami aff012;  Tomoko Norose aff013;  Nobuyuki Ohike aff013;  Masafumi Takimoto aff013;  Masahiko Izumizaki aff003;  Shinichi Kobayashi aff009;  Takuya Tsunoda aff002;  Satoshi Wada aff001
Působiště autorů: Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff001;  Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, Tokyo, Japan aff002;  Department of Physiology, Graduate School of Medicine, Showa University, Tokyo, Japan aff003;  Kanagawa Cancer Center Research Institute, Kanagawa, Japan aff004;  Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan aff005;  Noile-Immune Biotech, Inc., Tokyo, Japan aff006;  Department of Immunology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan aff007;  Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff008;  Clinical Research Institute for Clinical Pharmacology & Therapeutics, Showa University, Tokyo, Japan aff009;  Advanced Cancer Translational Research Institute, Showa University, Tokyo, Japan aff010;  Department of Innovative Immune-Oncology Therapeutics, Graduate School of Medicine, Gunma University, Gunma, Japan aff011;  Department of Surgery, Division of General and Gastroenterological Surgery, School of Medicine, Showa University, Tokyo, Japan aff012;  Department of Pathology and Laboratory Medicine, School of Medicine, Showa University, Tokyo, Japan aff013
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226707

Souhrn

Pancreatic cancer has an extremely poor prognosis, and identification of novel predictors of therapeutic efficacy and prognosis is urgently needed. Chemoresistance-related molecules are correlated with poor prognosis and may be effective targets for cancer treatment. Here, we aimed to identify novel molecules correlated with chemoresistance and poor prognosis in pancreatic cancer. We established 10 patient-derived xenograft (PDX) lines from patients with pancreatic cancer and performed next-generation sequencing (NGS) of tumor tissues from PDXs after treatment with standard drugs. We established a gene-transferred tumor cell line to express chemoresistance-related molecules and analyzed the chemoresistance of the established cell line against standard drugs. Finally, we performed immunohistochemical (IHC) analysis of chemoresistance-related molecules using 80 pancreatic cancer tissues. From NGS analysis, we identified olfactomedin-4 (OLFM4) as having high expression in the PDX group treated with anticancer drugs. In IHC analysis, OLFM4 expression was also high in PDXs administered anticancer drugs compared with that in untreated PDXs. Chemoresistance was observed by in vitro analysis of tumor cell lines with forced expression of OLFM4. In an assessment of tissue specimens from 80 patients with pancreatic cancer, Kaplan-Meier analysis showed that patients in the low OLFM4 expression group had a better survival rate than patients in the high OLFM4 expression group. Additionally, multivariate analysis showed that high expression of OLFM4 was an independent prognostic factor predicting poor outcomes. Overall, our study revealed that high expression of OLFM4 was involved in chemoresistance and was an independent prognostic factor in pancreatic cancer. OLFM4 may be a candidate therapeutic target in pancreatic cancer.

Klíčová slova:

Cancer treatment – Cancer detection and diagnosis – Mouse models – Cancer chemotherapy – Adenocarcinomas – Pancreatic cancer – Prognosis – Differentiated tumors


Zdroje

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68: 7–30. doi: 10.3322/caac.21442 29313949

2. Ministry of Health, Labour, and Welfare, Japan. National Vital Statistics in 2017. Available from: https://www.mhlw.go.jp/toukei/saikin/hw/jinkou/kakutei17/index.html. Accessed 03 November 2018 [in Japanese].

3. Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, et al. Pancreatic cancer. Nat Rev Dis Primers. 2016;2: 16022. doi: 10.1038/nrdp.2016.22 27158978

4. Gillen S, Schuster T, Zum Büschenfelde CM, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7: e1000267. doi: 10.1371/journal.pmed.1000267 20422030

5. Cecconi D, Palmieri M, Donadelli M. Proteomics in pancreatic cancer research. Proteomics. 2011;11: 816–828. doi: 10.1002/pmic.201000401 21229586

6. Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388: 73–85. doi: 10.1016/S0140-6736(16)00141-0 26830752

7. Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364: 1817–1825. doi: 10.1056/NEJMoa1011923 21561347

8. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369: 1691–1703. doi: 10.1056/NEJMoa1304369 24131140

9. Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387: 545–557. doi: 10.1016/S0140-6736(15)00986-1 26615328

10. Morton CL, Houghton PJ. Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc. 2007;2: 247–250. doi: 10.1038/nprot.2007.25 17406581

11. Jin K, Li G, Cui B, Zhang J, Lan H, Han N, et al. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases. PLoS One. 2011;6: e28384. doi: 10.1371/journal.pone.0028384 22164281

12. Johnson JI, Decker S, Zaharevitz D, Rubinstein LV, Venditti JM, Schepartz S, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer. 2001;84: 1424–1431. doi: 10.1054/bjoc.2001.1796 11355958

13. Sausville EA, Burger AM. Contributions of human tumor xenografts to anticancer drug development. Cancer Res. 2006;66: 3351–3354. doi: 10.1158/0008-5472.CAN-05-3627 16585151

14. Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C, et al. A molecularly annotated platform of patient-derived xenografts (‘xenopatients’) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2011;1: 508–523. doi: 10.1158/2159-8290.CD-11-0109 22586653

15. Galimi F, Torti D, Sassi F, Isella C, Corà D, Gastaldi S, et al. Genetic and expression analysis of MET, MACC1, and HGF in metastatic colorectal cancer: response to met inhibition in patient xenografts and pathologic correlations. Clin Cancer Res. 2011;17: 3146–3156. doi: 10.1158/1078-0432.CCR-10-3377 21447729

16. Morton CL, Houghton PJ. Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc. 2007;2: 247–250. doi: 10.1038/nprot.2007.25 17406581

17. Chijiwa T, Kawai K, Noguchi A, Sato H, Hayashi A, Cho H, et al. Establishment of patient-derived cancer xenografts in immunodeficient NOG mice. Int J Oncol. 2015;47: 61–70. doi: 10.3892/ijo.2015.2997 25963555

18. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10: R25. doi: 10.1186/gb-2009-10-3-r25 19261174

19. Komura D, Isagawa T, Kishi K, Suzuki R, Sato R, Tanaka M, et al. CASTIN: a system for comprehensive analysis of cancer-stromal interactome. BMC Genomics. 2016;17: 899. doi: 10.1186/s12864-016-3207-z 27829362

20. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834

21. Yada E, Wada S, Yoshida S, Sasada T. Use of patient-derived xenograft mouse models in cancer research and treatment. Future Sci OA. 2018;4: FSO271. doi: 10.4155/fsoa-2017-0136 29568561

22. Hidalgo M, Amant F, Biankin AV, Budinská E, Byrne AT, Caldas C, et al. Patient derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 2014;4: 998–1013. doi: 10.1158/2159-8290.CD-14-0001 25185190

23. Cho SY, Kang W, Han JY, Min S, Kang J, Lee A, et al. An integrative approach to precision cancer medicine using patient-derived xenografts. Mol Cells. 2016;39: 77–86. doi: 10.14348/molcells.2016.2350 26831452

24. Lefford H. US Cancer Institute to overhaul tumour cell lines. Nature. 2016;530: 391. doi: 10.1038/nature.2016.19364 26911756

25. de Sousa Abreu R, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol Biosyst. 2009;5: 1512–1526. doi: 10.1039/b908315d 20023718

26. Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al. Global quantification of mammalian gene expression control. Nature. 2011;473: 337–342. doi: 10.1038/nature10098 21593866

27. Wu L, Candille SI, Choi Y, Xie D, Jiang L, Li-Pook-Than J, et al. Variation and genetic control of protein abundance in humans. Nature. 2013;499: 79–82. doi: 10.1038/nature12223 23676674

28. Zhang B, Wang J, Wang X, Zhu J, Liu Q, Shi Z, et al. Proteogenomic characterization of human colon and rectal cancer. Nature. 2014;513: 382–387. doi: 10.1038/nature13438 25043054

29. Wulfkuhle JD, Liotta LA, Petricoin EF. Proteomic applications for the early detection of cancer. Nat Rev Cancer. 2003;3: 267–275. doi: 10.1038/nrc1043 12671665

30. Lim JE, Chien MW, Eaele CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237: 74–85. doi: 10.1097/00000658-200301000-00011 12496533

31. Matsuno S, Egawa S, Fukuyama S, Motoi F, Sunamura M, Isaji S, et al. Pancreatic Cancer Registry in Japan: 20 years of experience. Pancreas. 2004;28: 219–230. doi: 10.1097/00006676-200404000-00002 15084961

32. Guette C, Valo I, Vétillard A, Coqueret O. Olfactomedin-4 is a candidate biomarker of solid gastric, colorectal, pancreatic, head and neck, and prostate cancers. Proteomics Clin Appl. 2015;9: 58–63. doi: 10.1002/prca.201400083 25400027

33. Liu W, Zhu J, Cao L, Rodgers GP. Expression of hGC-1 is correlated with differentiation of gastric carcinoma. Histopathology. 2007;51: 157–165. doi: 10.1111/j.1365-2559.2007.02763.x 17650212

34. Yu L, He M, Yang Z, Chen G, Li M, Wang L, Chen S. Olfactomedin 4 is a marker for progression of cervical neoplasia. Int J Gynecol Cancer. 2011;21: 367–372. doi: 10.1097/IGC.0b013e31820866fe 21270618

35. Seko N, Oue N, Noguchi T, Sentani K, Sakamoto N, Hinoi T, et al. Olfactomedin 4 (GW112, hGC-1) is an independent prognostic marker for survival in patients with colorectal cancer. Exp Ther Med. 2010;1: 73–78. doi: 10.3892/etm_00000013 23136596

36. Chen L, Li H, Liu W, Zhu J, Zhao X, Wright E, et al. Olfactomedin 4 suppresses prostate cancer cell growth and metastasis via negative interaction with cathepsin D and SDF-1. Carcinogenesis. 2011;32: 986–994. doi: 10.1093/carcin/bgr065 21470957

37. Luo Z, Zhang Q, Zhao Z, Li B, Chen J, Wang Y. OLFM4 is associated with lymph node metastasis and poor prognosis in patients with gastric cancer. J Cancer Res Clin Oncol. 2011;137: 1713–1720. doi: 10.1007/s00432-011-1042-9 21904905

38. Li H, Rodriguez-Canales J, Liu W, Zhu J, Hanson JC, Pack S, et al. Deletion of the olfactomedin 4 gene is associated with progression of human prostate cancer. Am J Pathol. 2013;183: 1329–1338. doi: 10.1016/j.ajpath.2013.06.028 24070418

39. Takadate T, Onogawa T, Fukuda T, Motoi F, Suzuki T, Fujii K, et al. Novel prognostic protein markers of resectable pancreatic cancer identified by coupled shotgun and targeted proteomics using formalin-fixed paraffin-embedded tissues. Int J Cancer. 2013;132: 1368–1382. doi: 10.1002/ijc.27797 22915188

40. Duan C, Liu X, Liang S, Yang Z, Xia M, Wang L, et al. Oestrogen receptor-mediated expression of Olfactomedin 4 regulates the progression of endometrial adenocarcinoma. J Cell Mol Med. 2014;18: 863–874. doi: 10.1111/jcmm.12232 24495253

41. Su W, Luo L, Wu F, Lai Z, Li X, Xie Z, et al. Low expression of olfactomedin 4 correlates with poor prognosis in smoking patients with non-small cell lung cancer. Hum Pathol. 2015;46: 732–738. doi: 10.1016/j.humpath.2015.01.013 25771901

42. Jang BG, Lee BL, Kim WH. Olfactomedin-related proteins 4 (OLFM4) expression is involved in early gastric carcinogenesis and of prognostic significance in advanced gastric cancer. Virchows Arch. 2015;467: 285–294. doi: 10.1007/s00428-015-1793-9 26070873

43. Ma H, Tian T, Liang S, Liu X, Shen H, Xia M, et al. Estrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancer. Oncotarget. 2016;7: 10594–10605. doi: 10.18632/oncotarget.7236 26871282

44. Xiong B, Lei X, Zhang L, Fu J. The clinical significance and biological function of olfactomedin 4 in triple negative breast cancer. Biomed Pharmacother. 2017;86: 67–73. doi: 10.1016/j.biopha.2016.11.081 27939521

45. Mayama A, Takagi K, Suzuki H, Sato A, Onodera Y, Miki Y, et al. OLFM4, LY6D and S100A7 as potent markers for distant metastasis in estrogen receptor-positive breast carcinoma. Cancer Sci. 2018;109: 3350–3359. doi: 10.1111/cas.13770 30137688

46. Wang XY, Chen SH, Zhang YN, Xu CF. Olfactomedin-4 in digestive diseases: A mini-review. World J Gastroenterol. 2018 7;24: 1881–1887. doi: 10.3748/wjg.v24.i17.1881 29740203

47. Kobayashi D, Koshida S, Moriai R, Tsuji N, Watanabe N. Olfactomedin 4 promotes S-phase transition in proliferation of pancreatic cancer cells. Cancer Sci. 2007;98: 334–340. doi: 10.1111/j.1349-7006.2007.00397.x 17270022

48. Liu W, Liu Y, Zhu J, Wright E, Ding I, Rodgers GP. Reduced hGC-1 protein expression is associated with malignant progression of colon carcinoma. Clin Cancer Res. 2008;14: 1041–1049. doi: 10.1158/1078-0432.CCR-07-4125 18281536

49. Grover PK, Hardingham JE, Cummins AG. Stem cell marker olfactomedin 4: critical appraisal of its characteristics and role in tumorigenesis. Cancer Metastasis Rev. 2010;29: 761–775. doi: 10.1007/s10555-010-9262-z 20878207

50. Van Dussen KL, Carulli AJ, Keeley TM, Patel SR, Puthoff BJ, Magness ST, et al. Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells. Development. 2012;139: 488–497. doi: 10.1242/dev.070763 22190634

51. Liu W, Chen L, Zhu J, Rodgers GP. The glycoprotein hGC-1 binds to cadherin and lectins. Exp Cell Res. 2006;312: 1785–1797. doi: 10.1016/j.yexcr.2006.02.011 16566923

52. Zhang X, Huang Q, Yang Z, Li Y, Li CY. GW112, a novel antiapoptotic protein that promotes tumor growth. Cancer Res. 2004;64: 2474–2481. doi: 10.1158/0008-5472.can-03-3443 15059901

53. Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV. Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem. 2000;275: 33416–33426. doi: 10.1074/jbc.M003929200 10924506

54. Chidambaram NV, Angell JE, Ling W, Hofmann ER, Kalvakolanu DV. Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death. J Interferon Cytokine Res. 2000;20: 661–665. doi: 10.1089/107999000414844 10926209

55. Kim KK, Park KS, Song SB, Kim KE. Up regulation of GW112 gene by NF kappaB promotes an antiapoptotic property in gastric cancer cells. Mol Carcinog. 2010;49: 259–270. doi: 10.1002/mc.20596 19908244

56. Yan H, Lu D, Xu L, Xie Q, Dong X, Wu Y. Increased expression level of Olfactomedin4 in peripheral blood mononuclear cells of pancreatic adenocarcinoma patients. Hepatogastroenterology. 2011;58: 1354–1359. doi: 10.5754/hge10623 21937407


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