A Distinct Innate Immune Signature of Early Onset Colorectal Cancer.

Autor:	Gardner IH; Department of Surgery, Oregon Health & Science University, Portland, OR., Siddharthan R; Department of Surgery, Oregon Health & Science University, Portland, OR., Watson K; Department of Surgery, Oregon Health & Science University, Portland, OR., Dewey E; Department of Surgery, Oregon Health & Science University, Portland, OR., Ruhl R; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR., Khou S; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR., Guan X; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR.; Computational Biology Program, Oregon Health & Science University, Portland, OR; and., Xia Z; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR.; Computational Biology Program, Oregon Health & Science University, Portland, OR; and., Tsikitis VL; Department of Surgery, Oregon Health & Science University, Portland, OR., Anand S; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR; anands@ohsu.edu.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR.; Department of Radiation Medicine, Oregon Health & Science University, Portland, OR.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2021 Jun 23; Vol. 5 (6), pp. 489-499. Date of Electronic Publication: 2021 Jun 23.
DOI:	10.4049/immunohorizons.2000092
Abstrakt:	Despite a decrease in the prevalence of colorectal cancer (CRC) over the last 40 y, the prevalence of CRC in people under 50 y old is increasing around the globe. Early onset (≤50 y old) and late onset (≥65 y old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used NanoString immune profiling to analyze mRNA expression of immune genes in formalin-fixed paraffin-embedded surgical specimens from patients with early ( n = 40) and late onset ( n = 39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset CRC and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression-free survival, and increased expression of C7 was associated with worse overall survival. We also performed gain-of-function experiments with CFD and SAA1 in s.c. tumor models and found that CFD is associated with higher tumor volumes, impacted several immune genes, and impacted three genes in mice that were also found to be differentially expressed in early onset CRC (EGR1, PSMB9, and CXCL9). Our data demonstrate that the immune microenvironment, characterized by a distinct innate immune response signature in early onset CRC, is unique, location dependent, and might contribute to worse outcomes. (Copyright © 2021 The Authors.)
Databáze:	MEDLINE
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