Prognostic Molecular Classification of Appendiceal Mucinous Neoplasms Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
BACKGROUND: Appendiceal mucinous neoplasm (AMN) with peritoneal metastasis is a rare but deadly disease with few prognostic or therapy-predictive biomarkers to guide treatment decisions. Here, we investigated the prognostic and biological attributes of gene expression-based AMN molecular subtypes.
METHODS: AMN specimens (n = 138) derived from a population-based subseries of patients treated at our institution with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 05/2000 and 05/2013 were analyzed for gene expression using a custom-designed NanoString 148-gene panel. Signed non-negative matrix factorization (sNMF) was used to define a gene signature capable of delineating robustly-classified AMN molecular subtypes. The sNMF class assignments were evaluated by topology learning, reverse-graph embedding and cross-cohort performance analysis.
RESULTS: Three molecular subtypes of AMN were discerned by the expression patterns of 17 genes with roles in cancer progression or anti-tumor immunity. Tumor subtype assignments were confirmed by topology learning. AMN subtypes were termed immune-enriched (IE), oncogene-enriched (OE) and mixed (M) as evidenced by their gene expression patterns, and exhibited significantly different post-treatment survival outcomes. Genes with specialized immune functions, including markers of T-cells, natural killer cells, B-cells, and cytolytic activity showed increased expression in the low-risk IE subtype, while genes implicated in the promotion of cancer growth and progression were more highly expressed in the high-risk OE subtype. In multivariate analysis, the subtypes demonstrated independent prediction power for post-treatment survival.
CONCLUSIONS: Our findings suggest a greater role for the immune system in AMN than previously recognized. AMN subtypes may have clinical utility for predicting CRS/HIPEC treatment outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Annals of surgical oncology - 27(2020), 5 vom: 24. Mai, Seite 1439-1447 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Su, Jing [VerfasserIn] |
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| Anmerkungen: |
Date Completed 30.12.2020 Date Revised 02.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1245/s10434-020-08210-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305776304 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Appendiceal mucinous neoplasm (AMN) with peritoneal metastasis is a rare but deadly disease with few prognostic or therapy-predictive biomarkers to guide treatment decisions. Here, we investigated the prognostic and biological attributes of gene expression-based AMN molecular subtypes | ||
| 520 | |a METHODS: AMN specimens (n = 138) derived from a population-based subseries of patients treated at our institution with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) between 05/2000 and 05/2013 were analyzed for gene expression using a custom-designed NanoString 148-gene panel. Signed non-negative matrix factorization (sNMF) was used to define a gene signature capable of delineating robustly-classified AMN molecular subtypes. The sNMF class assignments were evaluated by topology learning, reverse-graph embedding and cross-cohort performance analysis | ||
| 520 | |a RESULTS: Three molecular subtypes of AMN were discerned by the expression patterns of 17 genes with roles in cancer progression or anti-tumor immunity. Tumor subtype assignments were confirmed by topology learning. AMN subtypes were termed immune-enriched (IE), oncogene-enriched (OE) and mixed (M) as evidenced by their gene expression patterns, and exhibited significantly different post-treatment survival outcomes. Genes with specialized immune functions, including markers of T-cells, natural killer cells, B-cells, and cytolytic activity showed increased expression in the low-risk IE subtype, while genes implicated in the promotion of cancer growth and progression were more highly expressed in the high-risk OE subtype. In multivariate analysis, the subtypes demonstrated independent prediction power for post-treatment survival | ||
| 520 | |a CONCLUSIONS: Our findings suggest a greater role for the immune system in AMN than previously recognized. AMN subtypes may have clinical utility for predicting CRS/HIPEC treatment outcomes | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Jin, Guangxu |e verfasserin |4 aut | |
| 700 | 1 | |a Votanopoulos, Konstantinos I |e verfasserin |4 aut | |
| 700 | 1 | |a Craddock, Lou |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Perry |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Jeff W |e verfasserin |4 aut | |
| 700 | 1 | |a Qasem, Shadi |e verfasserin |4 aut | |
| 700 | 1 | |a O'Neill, Stacey S |e verfasserin |4 aut | |
| 700 | 1 | |a Perry, Kathleen Cummins |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Lance D |e verfasserin |4 aut | |
| 700 | 1 | |a Levine, Edward A |e verfasserin |4 aut | |
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