Prognostic Value of ACVRL1 Expression in Metastatic Colorectal Cancer Patients Receiving First-Line Chemotherapy with Bevacizumab: Results from the TRIBE Study
| Autor: | Hanna, Diana L., Loupakis, Fotios, Yang, Dongyun, Cremolini, Chiara, Schirripa, Marta, Li, Meng, Matsusaka, Satoshi, Berger, Martin D., Miyamoto, Yuji, Zhang, Wu, Ning, Yan, Antoniotti, Carlotta, Salvatore, Lisa, Moran, Miriana, Zeger, Gary, Astrow, Stephanie H., Falcone, Alfredo, Lenz, Heinz-Josef |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Organoplatinum Compounds Colon Activin Receptors Type II Leucovorin Middle Aged Prognosis Article Progression-Free Survival Bevacizumab Italy Antineoplastic Combined Chemotherapy Protocols Biomarkers Tumor Disease Progression Humans Camptothecin Female Fluorouracil Prospective Studies RNA Messenger Colorectal Neoplasms Aged |
| Popis: | BACKGROUND: No biomarkers exist to predict benefit from anti-angiogenic therapy in metastatic colorectal cancer (mCRC) patients. ACVRL1 encodes for ALK1, a member of the transforming growth factor β (TGFβ) receptor family, which directs pathologic angiogenesis. We examined intratumoral expression of ACVRL1 and other angiogenesis pathway related genes to identify molecular markers in TRIBE. MATERIALS AND METHODS: Among 503 randomized patients, 228 had sufficient tissue for analysis. Formalin-fixed paraffin-embedded (FFPE) specimens were examined for expression of VEGF-A, VEGF-B, VEGF-C, VEGFR1, VEGFR2, ACVRL1, EphB4, and EGFL7 by RT-PCR. A maximal chi-square approach was used to determine mRNA levels associated with PFS, overall survival (OS), RR, early tumor shrinkage, and depth of response. Recursive partitioning (RP) trees were constructed to identify composite prognostic biomarker profiles. External validation was conducted in silico using the Oncomine database. RESULTS: High ACVRL1 expression was associated with superior OS in both treatment arms (FOLFOXIRI-bevacizumab: 32.7 vs. 13.5 months, HR 0.38, P=0.023; FOLFIRI-bevacizumab: 35.1 vs. 22.0 months, HR 0.36, P=0.006), and with prolonged PFS (11.7 vs. 5.9 months, multivariate HR 0.17, P=0.001) in patients receiving FOLFOXIRI-bevacizumab, in univariate and multivariate analyses. In RP analysis, ACVRL1 was the strongest discriminator of RR, PFS, and OS in patients receiving FOLFOXIRI-bevacizumab, and of OS in patients receiving FOLFIRI-bevacizumab. In silico validation revealed significant associations between ACVRL1 expression, disease recurrence, and 1-year survival (P |
| Databáze: | OpenAIRE |
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