Abstract 3125: Functional validation of respective gene from a nineteen gene-based risk score classifier, TCA19 as a prognostic indicator and response to immune system of colorectal cancer patients
Authors: Lee Jong Lyul , Kim Jin Cheon , Kim Chan Wook , Roh Seon Ae 
Published: August 2018

Background: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Pathologic staging is the gold standard for prognosis, concurrently selecting patients for adjuvant chemotherapy. A recent study reports that the risk score based 19 gene regulated by TREM1 or CTGF activation, TCA19, was an independent risk factor for disease-free survival.

Objective: The aim of this study was to validate TCA19 as a prognostic indicator of colorectal cancer patients and to select candidate genes related to clinicopathologic variables and immune system. Patients and Method: A retrospective review was conducted on patients who underwent surgery followed by adjuvant chemotherapy for CRC at the Asan Medical Center, Seoul, Korea, between December 2008 and December 2014. To validate TCA19, the medical records of 60 patients who met inclusion criteria were reviewed. According to the previous report, RNA sequencing using reverse transcription-quantitative polymerase chain reaction (RT-PCR) was done and then TCA19 risk score using 2ΔΔCt values was checked. After checking TCA19 genes, we selected key candidate genes according to the correlation with clinicopathologic variables and PFS. Immunohistochemistry (IHC), Western blot, and immunofluorescence staining (IFS) were done for the selected candidate genes, TREM1, CKS2, SLAMF7.

Results: Among 60 study cohort, 59 patients were in stage IV and 1 patient was in stage IIIC. Among 30 patients with high TCA risk score, the PFS rates between 4 patients who received 5-FU regimen and 8 patients received the target regimens (bevacizumab or cetuximab) were significantly different. On multivariate analyses for PFS, lymphovascular invasion (LVI), circumferential resection margin (CRM), SLAMF7, CKS2, and TREM1 were risk factors associated with PFS. Based on the association with clinicopathologic variables and the survival results, the SLAMF7, the CKS2, and the TREM1 can become a key gene among the TCA 19 genes in terms of prognostic factor and previous results. Primary and metastatic tumor IHC of the SLAMF7, the CKS2, and the TREM1 was significantly overexpressed, compared with normal tissue IHC of the three genes. Like IHC results, 5 days' IFS imaging of SLAMF7 after co-culture showed significant hypoexpression compared with 0 day imaging of SLAMF7.

Conclusion: TCA 19 risk score might be one of prognostic predictors related to using the target regimens (bevacizumab or cetuximab). TREM1, CKS2, and SLAMF7 were key candidate genes among the TCA19 genes in terms of clinicopathologic variables and survival outcomes. TREM1 was overexpressed in primary or metastatic tumor on the contrary; downregulation of SLAMF7 was shown in the primary or metastatic tumor. Further functional study using a large cohort will be needed.

Citation Format: Jong Lyul Lee, Jin Cheon Kim, Chan Wook Kim, Seon Ae Roh. Functional validation of respective gene from a nineteen gene-based risk score classifier, TCA19 as a prognostic indicator and response to immune system of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3125.