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- Title
Identification of a serum-based miRNA signature for response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy.
- Authors
Niwa, Yukiko; Yamada, Suguru; Sonohara, Fuminori; Kurimoto, Keisuke; Hayashi, Masamichi; Tashiro, Mitsuru; Iwata, Naoki; Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro
- Abstract
<bold>Background: </bold>Neoadjuvant chemotherapy (NAC) has become the standard of care for resectable esophageal squamous cell carcinoma (ESCC) which is one of the most lethal cancers, to improve resectability and prognosis. On this basis, to provide individually optimized therapy for ESCC, a minimally-invasive biomarker for response to NAC is strongly desired. This study aimed to identify the miRNA signature in serum specimens taken from ESCC patients undergoing NAC through genome-wide microarray technology.<bold>Methods: </bold>Comprehensive miRNA-expression profiles of serum specimens from ESCC patients before initial treatment were analyzed using microarray. A qPCR assay was performed to test the robustness of identified serum-based miRNA signature for discriminating response to NAC with serum specimens taken from 100 ESCC cases undergoing NAC.<bold>Results: </bold>We prioritized 62 miRNAs differentially expressed between responders and non-responders (absolute log2 fold change > 1.0, corresponding P < 0.05) and from the 62 miRNAs, we selected the miR-23a-5p, miR-193b-5p, and miR-873-3p, which were highly expressed in non-responders. Following qPCR analysis indicated the expression of miR-193b-5p and miR-873-3p in serum specimens were significantly higher in non-responders among three selected miRNAs (P = 0.004 and 0.001, respectively). Subsequently, we developed 2-miR-model (miR-193b-5p and miR-873-3p), 3-miR-model, and 2-miR + lymphatic invasion (ly) model based on logistic regression analysis, which achieved the better area under the receiver operating characteristic curves than those of single miRNAs as 2-miR-model, 0.70 (95% CI 0.57 to 0.82); 3-miR-model, 0.70 (95% CI 0.57 to 0.83); and 2-miR + ly, 0.73 (95% CI 0.60-0.86), respectively. Furthermore, we compared the detective power of the combined model: 2-miR + ly for discriminating non-responders to NAC, to other pretreatment clinical features. Consequently, 2-miR + ly model was superior to serum SCC antigen with great significance (P = 0.01) and to ly, and clinical T stage with marginal significance (P = 0.18, 0.07, respectively).<bold>Conclusions: </bold>Collectively, we demonstrated that the potential of a multi-miRNA biomarker for identifying NAC response in ESCC is realistic, and can be used in the clinic with the further validation.
- Subjects
TREATMENT of esophageal cancer; CANCER chemotherapy; SQUAMOUS cell carcinoma; POLYMERASE chain reaction; BIOMARKERS; THERAPEUTIC use of antineoplastic agents; RESEARCH; RESEARCH methodology; RNA; PROGNOSIS; ANTINEOPLASTIC agents; EVALUATION research; MEDICAL cooperation; COMPARATIVE studies; GENE expression profiling; GENES; RESEARCH funding; COMBINED modality therapy; RECEIVER operating characteristic curves; LOGISTIC regression analysis; PHARMACODYNAMICS
- Publication
Journal of Translational Medicine, 2019, Vol 17, Issue 1, pN.PAG
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-018-1762-6