Colorectal
Caroline Medin, MD
Resident
Emory University, United States
Disclosure: Disclosure information not submitted.
Over half of patients with colorectal cancer(CRC) develop liver metastases. While immunotherapy is an emerging treatment of solid tumors, its use among CRC patients is limited. Furthermore, gene expression patterns of liver-specific CRC metastases remain unclear. The purpose of this study was to identify a high-risk gene expression profile for patients with colorectal liver metastases(CRLM) to better inform prognosis and development of novel targeted therapies.
Methods:
Fifty-three FFPE CRLM samples from patients who underwent complete metastatectomy from 2009-2017 were examined. Expression profiling of extracted RNA was performed using NanoString Immuno-Oncology(IO360) 750-gene panel. High expression was defined as an absolute log 2-fold change≥1.5 and p-value<0.05. Patients were analyzed by extremes of outcomes: survival in the lowest quartile (high risk) compared to those still alive at last follow-up(survivors).
Results:
Thirty patients were included in final analysis. Median age was 58 years(IQR 20.5), 27% were female. Nine were high risk, with a median survival of 15 months. The 21 survivors had a median follow-up of 49 months. We identified 8 differentially expressed genes that were associated with poor survival: C7, IL6R, MGMT, CXCL2, PCK2, CSF1, and LILB4 were overexpressed; PLA2G2A was under-expressed(Figure 1).
Conclusions:
This study demonstrates differential gene expression associated with poor survival among patients with resected CRLM. Specific genes of interest include IL6R, MGMT, CSF1 and LILRB4. IL6R is a known effector of tumor proliferation via IL6 signaling from tumor-associated macrophages, myeloid-derived suppressor cells(MDSCs) and T-cells. MGMT repairs alkylating DNA damage and is implicated in carcinogenesis and chemotherapy response. CSF1 promotes M2-macrophage differentiation, suppressing inflammation and anti-tumor defense mechanisms. LILRB4 activation via MDSCs leads to T-cell inhibition. These overall suggest a myeloid-dominant tumor immune microenvironment and represent important potential therapeutic targets. Next steps include performing immunohistochemistry to validate findings at the protein level and investigate their tumor intrinsic role using human cell lines.