Published online Mar 21, 2019. doi: 10.3748/wjg.v25.i11.1341
Peer-review started: November 20, 2018
First decision: January 30, 2019
Revised: February 19, 2019
Accepted: February 22, 2019
Article in press: February 22, 2019
Published online: March 21, 2019
Our team previously developed a risk score system based a 19 gene-based scoring system (TCA19), worked as a prognostic factor in stage II-III colorectal cancer (CRC). Stage IV CRC is still challenging in the treatment including target-regimen and immunotherapy.
It is needed to identify whether the TCA19 scores predict survival outcomes in patients with stage IV CRC undergoing different chemotherapy regimens including target-regimen and 19 genes are related to immuno-oncology.
The current study aims to determine whether the TCA19 system can be used as a prognostic indicator for stage IV CRC and to identify possible target or marker genes associated with immune functions from 19 genes.
A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinico-pathologic variables, and progression-free survival (PFS). TCA19 gene expressions were determined by real-time quantitative polymerase chain reaction (RT-qPCR) in matched normal, primary tumor, and metastatic tumor tissues taken from the 60 study cohort. After selection of genes, related to immuno-oncology, expression of potential target or marker genes were examined by RT-qPCR, immunohistochemistry, western blot, and immunofluorescence staining using tissues from 10 validate set and in CRC cell lines co-cultured with monocytes in vitro.
In the patients with higher TCA19 score, the PFS rates of the patients with target-regimen were significantly higher than the patients with 5-fluorouracil-based regimen. In multivariable analysis, expression of signaling lymphocytic activation molecule family, member 7 (SLAMF7) and triggering receptor expressed on myeloid cells 1 (TREM1) was associated with PFS. From the results of the 10 validate set, down-regulation of SLAMF7 and up-regulation of TREM1 were observed in primary tumor and metastatic tumor tissues compared with normal tissue. In CRC cells expressing SLAMF7 that co-cultured with a monocytic cell line, levels of CD68 and CD73 in IFS imaging were significantly lower at day 5 of co-culture than at day 0. This result suggests that SLAMF7 may have an inhibitory role in the immune response.
The current study found an inhibitory role of the SLAMF7 in the immune response. Recently, it is known that the patients with microsatellite-high CRC may respond the immune therapy. In this concept, the direction of the future research is the role of SLAMF7 in the patients with stage IV CRC in terms of the immune therapy.