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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 13/2020

01-12-2020 | Glioma | Peritoneal Surface Malignancy

Clinical Implications of Genetic Signatures in Appendiceal Cancer Patients with Incomplete Cytoreduction/HIPEC

Authors: Omeed Moaven, MD, Jing Su, PhD, Guangxu Jin, PhD, Konstantinos I. Votanopoulos, MD, PhD, Perry Shen, MD, Christopher Mangieri, MD, Stacey S. O’Neill, MD, PhD, Kathleen C. Perry, MSc, Edward A. Levine, MD, Lance D. Miller, PhD

Published in: Annals of Surgical Oncology | Issue 13/2020

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Abstract

Introduction

Clinical decision-making is challenging in patients who undergo cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) when complete cytoreduction is not feasible. Nevertheless, some patients still benefit with long-term survival after incomplete CRS/HIPEC. There is currently no robust predictive tool that can assist clinical decision-making in this setting.

Methods

We quantified gene expression of 79 appendiceal mucinous neoplasms (AMN) from patients with incomplete CRS/HIPEC (R2 resection) using a custom NanoString gene panel. Using our previously defined, prognostic subtype classification algorithm based on signed nonnegative matrix factorization, we classified AMN cases into three molecular subtypes termed: immune enriched (IE), mixed (M), and oncogene enriched (OE). Kaplan–Meier and Cox proportional hazards analyses were used to associate subtypes and individual genes with overall survival (OS).

Results

Median overall survival (OS) was 7.7 years for IE, 3.6 years for M, and 1.4 years for OE. Compared with IE, OE was associated with significantly lower survival [hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.63–8.13; p = 0.0017]. The differences were observed in both low-grade and high-grade tumors. While only two genes were identified to be associated with OS in low-grade tumors, multiple genes were identified to be associated with OS in high-grade tumors, particularly genes with functions in cell cycle/proliferation, mucin production, immune pathways, and cell adhesion/migration.

Conclusion

Genetic signatures have prognostic value in patients with incomplete cytoreduction and provide valuable information to assist clinical and operative decision-making. Unraveling genetic alterations and involved pathways can direct efforts to design novel therapeutic modalities.
Appendix
Available only for authorised users
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Metadata
Title
Clinical Implications of Genetic Signatures in Appendiceal Cancer Patients with Incomplete Cytoreduction/HIPEC
Authors
Omeed Moaven, MD
Jing Su, PhD
Guangxu Jin, PhD
Konstantinos I. Votanopoulos, MD, PhD
Perry Shen, MD
Christopher Mangieri, MD
Stacey S. O’Neill, MD, PhD
Kathleen C. Perry, MSc
Edward A. Levine, MD
Lance D. Miller, PhD
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 13/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08841-8

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