Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes-Reference-Cited by-同舟云学术

Gene-Expression Profiling of Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with Adverse Outcomes

Published:2022-10-07 Issue:24 Volume:28 Page:5383-5395
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
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Author:

Meagher Nicola S.¹²^ORCID,Gorringe Kylie L.³⁴^ORCID,Wakefield Matthew⁵⁶⁷^ORCID,Bolithon Adelyn¹²^ORCID,Pang Chi Nam Ignatius⁸⁹^ORCID,Chiu Derek S.¹⁰^ORCID,Anglesio Michael S.¹⁰¹¹^ORCID,Mallitt Kylie-Ann¹¹²^ORCID,Doherty Jennifer A.¹³^ORCID,Harris Holly R.¹⁴¹⁵^ORCID,Schildkraut Joellen M.¹⁶^ORCID,Berchuck Andrew¹⁷^ORCID,Cushing-Haugen Kara L.¹⁴^ORCID,Chezar Ksenia¹⁸^ORCID,Chou Angela¹⁹²⁰²¹^ORCID,Tan Adeline²²²³^ORCID,Alsop Jennifer²⁴^ORCID,Barlow Ellen²⁵^ORCID,Beckmann Matthias W.²⁶^ORCID,Boros Jessica²¹²⁷²⁸^ORCID,Bowtell David D.L.³⁴^ORCID,Brand Alison H.²¹²⁸^ORCID,Brenton James D.²⁹^ORCID,Campbell Ian³⁴^ORCID,Cheasley Dane³⁴^ORCID,Cohen Joshua³⁰^ORCID,Cybulski Cezary³¹^ORCID,Elishaev Esther³²^ORCID,Erber Ramona³³^ORCID,Farrell Rhonda²¹³⁴^ORCID,Fischer Anna³⁵^ORCID,Fu Zhuxuan³⁶^ORCID,Gilks Blake³⁷^ORCID,Gill Anthony J.¹⁹²⁰²¹^ORCID,Gourley Charlie³⁸^ORCID,Grube Marcel³⁹^ORCID,Harnett Paul R.²¹⁴⁰^ORCID,Hartmann Arndt³⁵^ORCID,Hettiaratchi Anusha⁴¹^ORCID,Høgdall Claus K.⁴²^ORCID,Huzarski Tomasz³¹⁴³^ORCID,Jakubowska Anna³¹⁴⁴^ORCID,Jimenez-Linan Mercedes⁴⁵^ORCID,Kennedy Catherine J.²¹²⁷²⁸^ORCID,Kim Byoung-Gie⁴⁶^ORCID,Kim Jae-Weon⁴⁷^ORCID,Kim Jae-Hoon⁴⁸^ORCID,Klett Kayla⁴⁹^ORCID,Koziak Jennifer M.⁵⁰^ORCID,Lai Tiffany³⁰^ORCID,Laslavic Angela⁵¹^ORCID,Lester Jenny³⁰^ORCID,Leung Yee²²⁵²⁵³^ORCID,Li Na³⁵⁴^ORCID,Liauw Winston¹⁵⁵^ORCID,Lim Belle W.X.³^ORCID,Linder Anna⁵⁶^ORCID,Lubiński Jan³¹^ORCID,Mahale Sakshi³^ORCID,Mateoiu Constantina⁵⁷^ORCID,McInerny Simone³⁵⁴^ORCID,Menkiszak Janusz⁵⁸^ORCID,Minoo Parham¹⁸^ORCID,Mittelstadt Suzana³⁹^ORCID,Morris David⁵⁹^ORCID,Orsulic Sandra³⁰^ORCID,Park Sang-Yoon⁶⁰^ORCID,Pearce Celeste Leigh⁶¹⁶²^ORCID,Pearson John V.⁶³^ORCID,Pike Malcolm C.⁶²⁶⁴^ORCID,Quinn Carmel M.⁴¹^ORCID,Mohan Ganendra Raj⁵²⁶⁵⁶⁶^ORCID,Rao Jianyu⁶⁷^ORCID,Riggan Marjorie J.¹⁷^ORCID,Ruebner Matthias²⁶^ORCID,Salfinger Stuart⁶⁵^ORCID,Scott Clare L.⁴⁵⁶⁷^ORCID,Shah Mitul²⁴^ORCID,Steed Helen⁶⁸⁶⁹^ORCID,Stewart Colin J.R.⁷⁰^ORCID,Subramanian Deepak³^ORCID,Sung Soseul⁷¹⁷²⁷³^ORCID,Tang Katrina⁷⁴^ORCID,Timpson Paul¹⁹^ORCID,Ward Robyn L.²¹^ORCID,Wiedenhoefer Rebekka³⁵^ORCID,Thorne Heather³^ORCID,Cohen Paul A.²²⁷⁵^ORCID,Crowe Philip¹⁷⁶^ORCID,Fasching Peter A.²⁶^ORCID,Gronwald Jacek³¹^ORCID,Hawkins Nicholas J.¹^ORCID,Høgdall Estrid⁷⁷^ORCID,Huntsman David G.¹¹⁷⁸^ORCID,James Paul A.³⁵⁴^ORCID,Karlan Beth Y.³⁰^ORCID,Kelemen Linda E.⁷⁹^ORCID,Kommoss Stefan³⁹^ORCID,Konecny Gottfried E.³⁰^ORCID,Modugno Francesmary³⁶⁴⁹⁵¹^ORCID,Park Sue K.⁷²⁷³⁸⁰^ORCID,Staebler Annette³⁵^ORCID,Sundfeldt Karin⁵⁶^ORCID,Wu Anna H.⁶²^ORCID,Talhouk Aline¹⁰¹¹³⁷^ORCID,Pharoah Paul D.P.²⁴⁸¹^ORCID,Anderson Lyndal²¹⁸²^ORCID,DeFazio Anna²¹²⁷²⁸⁸³^ORCID,Köbel Martin¹⁸^ORCID,Friedlander Michael L.¹²⁵⁸⁴^ORCID,Ramus Susan J.¹²^ORCID, , ,

Affiliation:

1. 1School of Clinical Medicine, Faculty of Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.

2. 2Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia.

3. 3Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

4. 4Sir Peter MacCallum Department of Medical Oncology, The University of Melbourne, Parkville, Victoria, Australia.

5. 5The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.

6. 6Department of Medical Biology, The University of Melbourne, Melbourne, Victoria, Australia.

7. 7Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Victoria, Australia.

8. 8School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia.

9. 9Bioinformatics Unit, Children's Medical Research Institute, Westmead, Sydney, Australia.

10. 10British Columbia's Gynecological Cancer Research Team (OVCARE), University of British Columbia, BC Cancer, and Vancouver General Hospital, Vancouver, British Columbia, Canada.

11. 11Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.

12. 12Centre for Big Data Research in Health, University of New South Wales Sydney, Sydney, New South Wales, Australia.

13. 13Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

14. 14Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.

15. 15Department of Epidemiology, University of Washington, Seattle, Washington.

16. 16Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.

17. 17Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina.

18. 18Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada.

19. 19The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.

20. 20Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.

21. 21The University of Sydney, Sydney, New South Wales, Australia.

22. 22Division of Obstetrics and Gynaecology, Medical School, University of Western Australia, Crawley, Western Australia, Australia.

23. 23Western Women's Pathology, Western Diagnostic Pathology, Wembley, Western Australia, Australia.

24. 24Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.

25. 25Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, New South Wales, Australia.

26. 26Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.

27. 27Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.

28. 28Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.

29. 29Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.

30. 30David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, California.

31. 31Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.

32. 32Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

33. 33Institute of Pathology, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander Universität Erlangen-Nürnberg, University Hospital Erlangen, Erlangen, Germany.

34. 34Prince of Wales Private Hospital, Randwick, New South Wales, Australia.

35. 35Institute of Pathology and Neuropathology, Tübingen University Hospital, Tübingen, Germany.

36. 36Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania.

37. 37Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

38. 38Nicola Murray Centre for Ovarian Cancer Research, Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh, United Kingdom.

39. 39Department of Women's Health, Tübingen University Hospital, Tübingen, Germany.

40. 40Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.

41. 41The Health Precincts Biobank (formerly the Health Science Alliance Biobank), UNSW Biospecimen Services, Mark Wainwright Analytical Centre, University of New South Wales Sydney, Sydney, New South Wales, Australia.

42. 42Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

43. 43Department of Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland.

44. 44Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.

45. 45Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom.

46. 46Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

47. 47Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

48. 48Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

49. 49Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, Pennsylvania.

50. 50Alberta Health Services-Cancer Care, Calgary, Alberta, Canada.

51. 51Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

52. 52Department of Gynaecological Oncology, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.

53. 53Australia New Zealand Gynaecological Oncology Group, Camperdown, New South Wales, Australia.

54. 54Parkville Familial Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

55. 55Cancer Care Centre, St George Hospital, Sydney, New South Wales, Australia.

56. 56Department of Obstetrics and Gynecology, Inst of Clinical Science, Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, Sweden.

57. 57Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.

58. 58Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.

59. 59St George and Sutherland Clinical School, University of New South Wales Sydney, Sydney, New South Wales, Australia.

60. 60Center for Gynecologic Cancer, National Cancer Center Institute for Cancer Control, Goyang, Republic of Korea.

61. 61Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.

62. 62Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.

63. 63QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

64. 64Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.

65. 65Department of Gynaecological Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia.

66. 66School of Medicine, University of Notre Dame, Fremantle, Western Australia, Australia.

67. 67Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.

68. 68Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.

69. 69Section of Gynecologic Oncology Surgery, North Zone, Alberta Health Services, Edmonton, Alberta, Canada.

70. 70School for Women's and Infants' Health, University of Western Australia, Perth, Western Australia, Australia.

71. 71Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.

72. 72Cancer Research Institute, Seoul National University, Seoul, Korea.

73. 73Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

74. 74Department of Anatomical Pathology, Prince of Wales Hospital, Sydney, New South Wales, Australia.

75. 75Department of Gynaecological Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia.

76. 76Department of Surgery, Prince of Wales Private Hospital, Randwick, New South Wales, Australia.

77. 77Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.

78. 78Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, British Columbia, Canada.

79. 79Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.

80. 80Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, South Korea.

81. 81Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

82. 82Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia.

83. 83The Daffodil Centre, a joint venture with Cancer Council NSW, The University of Sydney, Sydney, New South Wales, Australia.

84. 84Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia.

Abstract

Abstract Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Funder

National Health and Medical Research Council

New South Wales Ministry of Health

University of New South Wales

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-1206/3212870/ccr-22-1206.pdf

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