title: Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: angiogenic markers of neoadjuvant chemoradiation.
abstract: The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor 1α (HIF‑1α), vascular endothelial growth factor (VEGF), stromal cell‑derived factor 1α (SDF-1α) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1α protein was downregulated after NCRT in the rectal cancer tissues (P<0.001, P=0.001 and P=0.044, respectively). However, SDF-1α was upregulated after NCRT (P<0.001). Moreover, upregulated expression of SDF-1α (P=0.016) and positive PlGF staining (P=0.001) after NCRT were significantly associated with resistance to NCRT. On multivariate analysis, positive PlGF staining after NCRT was found to be independently associated with resistance to NCRT (P=0.013). Our data suggest that SDF-1α and PlGF should be evaluated as new targets for NCRT in LARC.
authors.affiliation: Department of Internal Medicine, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Han Jo
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Sang Byung
authors.initials: SB
authors.lastname: Bae
authors.affiliation: Department of Pathology, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Department of Radiation Oncology, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Eun Seog
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Surgery, Eulji University College of Medicine, Daejeon, Republic of Korea.
authors.forename: Chang-Nam
authors.initials: CN
authors.lastname: Kim
authors.affiliation: Department of Surgery, Dankook University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Dong-Guk
authors.initials: DG
authors.lastname: Park
authors.affiliation: Department of Surgery, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Ahn
authors.affiliation: Department of Surgery, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Surgery, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Eung Jin
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Department of Surgery, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Moon Soo
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Soonchunhayng University College of Medicine, Cheonan, Republic of Korea.
authors.forename: Moo Jun
authors.initials: MJ
authors.lastname: Baek
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000628:therapy; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D054377:Chemokine CXCL12; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; C098069:PIGF protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A