Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer
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- Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer
- J L Lee; S A Roh; C W Kim; Y H Kwon; Y J Ha; Seon-Kyu Kim; Seon-Young Kim; D H Cho; Yong Sung Kim; J C Kim
- Bibliographic Citation
- World Journal of Gastroenterology, vol. 25, no. 11, pp. 1341-1354
- Publication Year
Genomic profiling of tumors has contributed to the understanding of colorectal
cancer (CRC), facilitating diagnosis, prognosis and selection of treatments,
including targeted regimens. A report suggested that a 19-gene-based risk
classifier (TCA19) was a prognostic tool for patients with stage III CRC. The
survival outcomes in patients with stage IV CRC are still poor and appropriate
selection of targeted therapies and immunotherapies is challenging.
To assess clinical implication of TCA19 in patients with stage IV CRC, and to
identify TCA19 with involvement in immune-oncology.
A retrospective review of the medical records of 60 patients with stage IV CRC
was conducted, assessing clinicopathological variables and progression-free
survival (PFS). TCA19 gene expression was determined by quantitative
polymerase chain reaction (qPCR) in matched normal and tumor tissues taken
from the study cohort. Expression of potential immune-oncology regulatory
proteins and targets was examined by immunohistochemistry (IHC), western
blot, immunofluorescence staining in tissues from a validation cohort of 10
patients, and in CRC cell lines co-cultured with monocyte in vitro.
In the patients with TCA19 score higher than the median, the PFS rates of eight
patients who received the targeted regimens were significantly higher than the
PFS rates of four patients who received 5-fluorouracil-based regimen (P = 0.041).
In multivariate analysis, expression of signaling lymphocytic activation molecule
family, member 7 (SLAMF7) and triggering receptor expressed on myeloid cells 1
(TREM1) was associated with PFS in the 60-patient cohort. After checking
another 10 validate set, the expression of the IHC, the level of real-time qPCR,
and the level of western blot were lower for SLAMF7 and higher for TREM7 in
primary and metastatic tumors than in normal tissues. In CRC cells expressing
SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD
73 were significantly lower at day 5 of co-culture than at day 0.
The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV
CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in
primary and metastatic tumor tissues.
- Colorectal cancer; Prognosis; Immunotherapy; Signaling lymphocytic activation molecule family, member 7; Triggering receptor expressed on myeloid cells 1
- Baishideng Publishing Group Inc
- Appears in Collections:
- Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Korea Bioinformation Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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