Background. Radiotherapy is increasingly used in preoperative approaches for locally advanced rectal cancer to reduce local recurrence. However, the principal limitation is large variability in response among different individuals due to tumor heterogeneity. In current study, we compared gene expression profiles between radiation responder and non-responder in cancerous tissues to identify radiation-related molecules that can be used to evaluate the tumor response of radiation.

Methods. We investigated five genes (CDC25A, VAV1, TP73, BRCA1 and ZAP70) which were significantly related to prognostic factors (tumor size, advanced stage, invasive depth, lymph node metastasis and differentiation) from 110 colorectal cancer tissues confirmed by membrane array and RT-PCR methods in our previous study. Therefore, we further investigate those protein overexpressions by immunohistochemical stain in pretherapeutic rectal cancerous tissues. The expression profiles were evaluated according to the frequency of positive staining in the cytoplasm and/or nucleus of cancer cells. Its expression was classified as positive in cases with more than 50% positive-stained cells, with other samples being classified as negative. Cancer tissues that expressed scores of + were regarded as the overexpression group, whereas those with scores of negative staining were regarded as the non-overexpression group.

Results. We focused on these 5 genes and validated data with pretherapeutic biopsies from 36 locally advanced rectal cancer patients, and found that overexpression of CDC25A, VAV1 and ZAP70 were correlated with tumor response (P=0.001, 0.033, and 0.016, respectively). The multivariate logistic regressions with adjustment of age, sex and stage, CDC25A overexpression more than 2-fold were significantly correlated with tumor response (OR = 2.667, 95%CI = 1.591-4.470, P=0.03). Positive findings of CDC25A immunohistochemistry stain were also present in the tumor specimens of responders.

Conclusion. We identified radiation-related genes in rectal cancer and demonstrated that CDC25A may play an important role in response to radiotherapy. These findings suggest that CDC25A may be a novel marker for predicting the effectiveness of radiotherapy in clinical patients.

Note: This abstract was not presented at the meeting.

Citation Format: Ming-Yii Huang. CDC25A overexpression is correlated with tumor response to radiotherapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2791. doi:10.1158/1538-7445.AM2017-2791

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.