A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.
In: Gastroenterology (00165085), Jg. 161 (2021-07-01), Heft 1, S. 151-151
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Zugriff:
We recently reported use of tissue-based transcriptomic biomarkers (microRNA [miRNA] or messenger RNA [mRNA]) for identification of lymph node metastasis (LNM) in patients with invasive submucosal colorectal cancers (T1 CRC). In this study, we translated our tissue-based biomarkers into a blood-based liquid biopsy assay for noninvasive detection of LNM in patients with high-risk T1 CRC. We analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from 2 clinical cohorts—a training cohort (N = 46) and a validation cohort (N = 142)—and matched formalin-fixed paraffin-embedded samples (N = 142). We performed quantitative reverse-transcription polymerase chain reaction, followed by logistic regression analysis, to develop an integrated transcriptomic panel and establish a risk-stratification model combined with clinical risk factors. We used comprehensive expression profiling of a training cohort of LNM-positive and LMN-negative serum specimens to identify an optimized transcriptomic panel of 4 miRNAs (miR-181b, miR-193b, miR-195, and miR-411) and 5 mRNAs (AMT , forkhead box A1 [ FOXA1 ], polymeric immunoglobulin receptor [ PIGR ], matrix metalloproteinase 1 [ MMP1 ], and matrix metalloproteinase 9 [ MMP9 ]), which robustly identified patients with LNM (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.72–0.94). We validated panel performance in an independent validation cohort (AUC, 0.82; 95% CI, 0.74–0.88). Our risk-stratification model was more accurate than the panel and an independent predictor for identification of LNM (AUC, 0.90; univariate: odds ratio [OR], 37.17; 95% CI, 4.48–308.35; P <.001; multivariate: OR, 17.28; 95% CI, 1.82–164.07; P =.013). The model limited potential overtreatment to only 18% of all patients, which is dramatically superior to pathologic features that are currently used (92%). A novel risk-stratification model for noninvasive identification of T1 CRC has the potential to avoid unnecessary operations for patients classified as high-risk by conventional risk-classification criteria. A novel biomarker signature can distinguish patients with high-risk invasive submucosal colorectal cancers who have lymph node metastasis from those who do not. [ABSTRACT FROM AUTHOR]
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Titel: |
A Liquid Biopsy Assay for Noninvasive Identification of Lymph Node Metastases in T1 Colorectal Cancer.
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Autor/in / Beteiligte Person: | Wada, Yuma ; Shimada, Mitsuo ; Murano, Tatsuro ; Takamaru, Hiroyuki ; Morine, Yuji ; Ikemoto, Tetsuya ; Saito, Yu ; Balaguer, Francesc ; Bujanda, Luis ; Pellise, Maria ; Kato, Ken ; Saito, Yutaka ; Ikematsu, Hiroaki ; Goel, Ajay |
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Zeitschrift: | Gastroenterology (00165085), Jg. 161 (2021-07-01), Heft 1, S. 151-151 |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
ISSN: | 0016-5085 (print) |
DOI: | 10.1053/j.gastro.2021.03.062 |
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