title: Molecular biomarkers correlate with disease-free survival in patients with anal canal carcinoma treated with chemoradiation.
abstract: Large primary tumor and clinical nodal involvement in patients with anal carcinoma treated with chemoradiation are associated with poor disease-free survival (DFS). However, the outcome in individual patient is unpredictable. We hypothesized that biomarkers related to chemotherapy and/or radiation resistance would be associated with DFS. We analyzed clinical and biomarker data in 30 patients with anal carcinoma who had chemoradiation. Patient selection was based on the availability of untreated cancer for biomarkers, completion of prescribed chemoradiation, and patient outcomes (~50% disease-free) nonrepresentative of published cohorts but conducive to biomarker discovery. Ten biomarkers, Ki67, human telomerase (hTERT), epidermal growth factor receptor (EGFR), p53, p16, Bcl-2, vascular endothelial growth factor (VEGF), nuclear factor kappa-B (NF-kappaB), SHH, and Gli-1, were studied. Raw data as continuous variable (only EGFR was trichotomized) were analyzed. Univariate and multivariate Cox models were utilized to assess relationship between DFS and biomarkers. Twenty-three of 30 patients were women, tumor diameter was >5 cm in 30, and 37% had clinically positive nodes. Fourteen (30%) patients had a DFS event after chemoradiation. In univariate analysis, NF-kappaB (P = 0.01), SHH (P = 0.02), Gli-1 (P = 0.02), and tumor diameter (P = 0.03) were significantly associated with DFS, and Ki67 (P = 0.07) was marginally significant. In multivariate analysis, tumor diameter (P = 0.003), Ki67 (P = 0.005), NF-kappaB (P = 0.002), SHH (P = 0.02), and Gli-1 (P = 0.02) were significantly associated with DFS. Our data, albeit preliminary, suggest that several biomarkers (Ki67, NF-kappaB, SHH, and Gli-1) are associated with DFS. Upon further expansion and validation, these results may provide a biomarker-based understanding of heterogeneous clinical biology of patients with anal carcinoma.
authors.affiliation: Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. jajani@mdanderson.org
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Julie G
authors.initials: JG
authors.lastname: Izzo
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Crane
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: John M
authors.initials: JM
authors.lastname: Skibber
authors.forename: Prajnan
authors.initials: P
authors.lastname: Das
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
mesh_terms: D001003:Anal Canal / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D053823:Hedgehog Proteins / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis*; D016328:NF-kappa B / Q000032:analysis*; D011379:Prognosis; D011879:Radiotherapy Dosage; D014157:Transcription Factors / Q000032:analysis*; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D019394:Ki-67 Antigen; D016328:NF-kappa B; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D002945:Cisplatin; D005472:Fluorouracil