title: Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.
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.
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Aziz
authors.initials: A
authors.lastname: Zaanan
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Jae Myung
authors.initials: JM
authors.lastname: Park
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: David
authors.initials: D
authors.lastname: Tougeron
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Shengbing
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Biomedical Statistics and Informatics, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo Cancer Center, Rochester, MN.|Department of Oncology, Mayo Clinic and Mayo Cancer Center, Rochester, MN.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000071186:Beclin-1; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging / Q000379:methods; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins
keywords: autophagy; beclin 1; biomarker; chemoradiation; rectal cancer