Abstract 353: Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer
Authors: Chen Chung-Yu , Lai Peng-Sheng , Chen Ying-Yin , Lin Long-Wei 
Published: September 2020

Background: Administration of postoperative adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival for patients with resected colorectal cancer (CRC). Regarding the prognostic factors, including pathologic features and gene mutation have major relevance for stage III disease, it is not well known whether they might help select patients who would fare favorably when received adjuvant chemotherapy.

OBJECTIVE: Expression of astrocyte-elevated gene-1 (AEG-1), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) were needed to investigate the role involved in adjuvant combination therapy for patients with resectable stage III colon cancer.

Methods: AEG-1, TS, ERCC1, EGFR and VEGF were investigated by CRC cell lines and intra-tumor immunohistochemistry stain. Furthermore, this study collected 29 patients with stage III colorectal cancer who underwent surgical resection from 2011 to 2016 and received postoperative adjuvant chemotherapy. The culmination of clinical data registration included surgical procedures, tumor size, number of lymph node metastases, and types of chemotherapy drugs.

Result: A significant positive correlation between AEG-1, TS, ERCC1, EGFR, and VEGF gene expression levels were revealed in CRC cell lines. Cell lines with lower AEG-1 and TS expression had higher sensitivity to 5-FU treatment. In clinical studies, we found that higher AEG-1 expression was noted in T4 and also caused CRC recurrence or metastasis. Patients with T4 and stage IIIC CRC had a significantly shorter DFS (T4 v.s. T1-3, DFS, months, median: 4.1 ± 1.2 v.s. non-reach [NR], p &lt; 0.001; IIIC v.s. IIIA or IIIB, DFS, months, median: 10.6 ± 5.3 v.s. NR, p = 0.037; respectively). Patients with higher AEG-1 and TS expression had a shorter DFS (AEG-1, high v.s. low, months, median: 12.8 ± 2.4 v.s. NR, p = 0.003; TS, high v.s. low, months, median: 13.8 ± 2.3 v.s. NR, p = 0.012; respectively). In multivariate Cox Regression analysis, advanced tumor invasion (T4) and high AEG-1 expression could be an independent prognostic factor to cause poor survival in resectable stage III CRC patients treated with adjuvant chemotherapy.

Conclusion: Expressions of AEG-1 and tumor grade as a candidate prognostic factor of recurrence in stage III colorectal cancer patients receiving adjuvant fluoropyrimidine-based chemotherapy. A prospective cohort study should be guaranteed to validate these factors to be predictive markers of adjuvant chemotherapy benefit for stage III CRC.

Citation Format: Chung-Yu Chen, Peng-Sheng Lai, Ying-Yin Chen, Long-Wei Lin. Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 353.