期刊
CLINICAL CANCER RESEARCH
卷 28, 期 24, 页码 5383-5395出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-22-1206
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资金
- U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia [191, 211, 182]
- Cancer Council Tasmania
- National Health and Medical Research Council of Australia (NHMRC) [ID199600, ID400413, ID400281, APP1023698, 1092856, APP2009840, APP1117044, APP1092856]
- Canadian Institutes of Health Research [MOP-86727]
- ELAN Funds of the University of Erlangen-Nuremberg
- NCI/NIH [R01CA168758, R01CA112523, R01CA087538]
- Translational Cancer Research Network - Cancer Institute NSW
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
- National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [HI16C1127, 0920010]
- University of Pittsburgh School of Medicine Dean's Faculty Advancement Award
- National Science Foundation [DGE-2217399-Modugno]
- National Cancer Institute [P30CA047904]
- Cancer Research UK [C490/A16561, A22905, A15601, A17197]
- UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Cambridge Cancer Centre
- BC Cancer Foundation
- VGH and UBC Hospital Foundation
- National Health and Medical Research Council of Australia [310670, 628903]
- Cancer Institute NSW [12/RIG/1-17, 15/RIG/1-16, 15/TRC/1-01]
- Sydney West Translational Cancer Research Centre - Cancer Institute NSW
- NSW Ministry of Health
- UNSW Sydney under the NSW Health PhD Scholarship Program
- Translational Cancer Research Network
- U.S. Department of Defense [OC170121]
- Australian National Health and Medical Research Council
- Peter MacCallum Cancer Foundation
- U.S. Department of Defense (DoD) Ovarian Cancer Transitional Leverage Award [W81XWH-12-1-0104]
- Calgary Laboratory Services research support fund [RS19-612]
- Ovarian Cancer Research Fund (OCRF)
- Michael Smith Foundation for Health Research Scholar Award
- Janet D. Cottrelle Foundation Scholars programme
- Dr. Chew Wei Memorial Professorship in Gynecologic Oncology
- Canada Research Chairs programme (Research Chair in Molecular and Genomic Pathology)
- American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]
- National Center for Advancing Translational Sciences (NCATS) [UL1TR000124]
- Swedish Cancer Foundation [CAN 18-384]
- Swedish government [ALFGBG965552]
- Swedish county council [ALFGBG965552]
- [002/RID/2018/19]
- Korea Health Promotion Institute [0920010] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Clinical and gene expression data were analyzed to identify prognostic and diagnostic features of advanced-stage mucinous ovarian carcinoma (MOC) and differentiate it from gastrointestinal (GI) metastases. An infiltrative growth pattern was associated with poor prognosis, and high expression of THBS2 and TAGLN was linked to adverse prognosis in MOC. HER2 amplification or high mRNA expression was detected in some MOC cases, suggesting the potential of HER2-targeted therapy. MOC samples clustered with upper GI tumors, indicating similar biology and treatment strategies.
Purpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primaryMOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and geneexpression 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.
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