Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma

Aziz Zaanan, Jae Myung Park, David Tougeron, Shengbing Huang, Tsung Teh Wu, Nathan R. Foster, Frank A. Sinicrope

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Beclin 1 is an essential regulator of autophagy that is induced in response to cellular stress and serves to maintain cell survival in established tumors. We recently demonstrated that Beclin 1 suppression can sensitize colorectal cancer cells to radiation-induced DNA damage and apoptosis. Therefore, we hypothesized that the level of Beclin 1 expression may be associated with radiation sensitivity in vivo. We determined the association of Beclin 1 expression in pretreatment rectal cancer tissues with response to neoadjuvant chemoradiation in surgical resection specimens. Stages II and III (n=96) rectal adenocarcinoma patients were treated with neoadjuvant chemoradiation followed by surgical resection with curative intent. Beclin 1 was analyzed by immunohistochemistry and the expression level was dichotomized at the median value with categorization into low and high groups. We identified 56 (58.3%) and 40 (41.7%) patients whose tumors had high- versus low-level Beclin 1 expression, respectively. Rectal cancers with high versus low Beclin 1 expression were significantly less likely to be downstaged after chemoradiation treatment (45% [25/55] vs. 58% [22/38]; p=0.02). In a multivariable analysis adjusted for age, sex, histological grade and baseline tumor node metastasis (TNM) stage, the impact of Beclin 1 expression on tumor downstaging remained statistically significant (p=0.03). The association of the level of Beclin 1 expression with the rate of tumor downstaging after chemoradiation is consistent with in vitro data, and suggests that Beclin 1 may be a predictive biomarker for the efficacy of chemoradiation in patients with rectal cancer. What's new? Patients with nonmetastatic rectal cancer routinely receive chemotherapy and radiation before surgery. However, a predictive marker for the efficacy of chemoradiation is lacking. Here, the authors show that the essential autophagy protein Beclin 1 -known to protect against radiation-induced DNA damage- could be such a predictive marker. In locally advanced rectal cancer patients, high-level Beclin 1 expression in pretreatment tumor tissues was associated with a significantly reduced rate of tumor downstaging after chemoradiation and vice versa, supporting a new role of Beclin 1 as a clinical biomarker.

Original languageEnglish (US)
Pages (from-to)1498-1502
Number of pages5
JournalInternational Journal of Cancer
Volume137
Issue number6
DOIs
StatePublished - Sep 1 2015

Keywords

  • autophagy
  • beclin 1
  • biomarker
  • chemoradiation
  • rectal cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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