Biomarker Signature May Identify Patients With High-Risk T1 CRC and Lymph Node Metastases

Researchers tested a novel liquid biopsy assay for detection of lymph node metastasis in patients with high-risk T1 CRC.

Researchers have developed a risk-stratification model that can help detect lymph node metastases (LNM) in a liquid biopsy assay, providing more robust and accurate identification of patients with high-risk T1 colorectal cancers (CRC). These findings according to a study published in Gastroenterology.

The investigators analyzed 330 samples from patients with high-risk T1 CRC, including 188 serum specimens from 2 cohorts: a training cohort (n = 46; 5 LNM-positive [LNP] and 41 LNM-negative [LNN] patients) and a validation cohort (n = 142; 12 LNP and 130 LNN patients) from a hospital in Japan. Matched formalin-fixed paraffin-embedded (n = 142) specimens were also obtained from participants in the validation cohort. Patients underwent radical surgeries from January to December 2017 in the training cohort, and from January 2011 to December 2017 in the validation cohort.

The researchers performed real-time, quantitative reverse transcription polymerase chain reaction and logistic regression analysis to develop an integrated transcriptomic panel and establish a risk-stratification model. Comprehensive expression profiling was used to identify an optimized transcriptomic panel of 4 micro-ribonucleic acids ([miRNAs] miR-181b, miR-193b, miR-195, miR-411) and 5 messenger-ribonucleic acids ([mRNAs] AMT, FOXA1, PIGR, MMP1, MMP9).

Identification of LNM was superior when all 4 miRNAs and 5 mRNAs were used to establish a combined transcriptomic panel (area under the curve [AUC] = 0.86; 95% CI, 0.72-0.94). After the signature in matched blood serum specimens was assessed, the diagnostic accuracy was similar to the findings from tissue specimens (AUC = 0.82; 95% CI, 0.74-0.88).

Univariate and multivariate logistic regression analysis showed that the risk-stratification model was superior to the panel and was an independent predictor of LNM (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) in the validation cohort.

Among the 32 patients who were considered high risk, 9 had LNM (7%), suggesting that 18% (23 of 130) of participants with T1 CRC may have been over-treated. This finding is “dramatically superior” compared with currently used pathologic features (92% vs 18%), according to the study authors.

“This highlights the potential for using our liquid biopsy-based risk-assessment model in patients with high-risk T1 CRC,” they commented.

The researchers noted several limitations, including the retrospective design and limited sample size. Additionally, the study used training and validation cohorts of patients from Japan with similar clinicopathologic characteristics, limiting potential variation.

“Pending validation in future prospective studies, our findings highlight the potential clinical impact of our model for improved selection of patients with high-risk T1 CRC, which will reduce the overall burden of unnecessary surgeries and expenses associated with these procedures, and improve the overall management of patients with this malignancy,” the investigators concluded.


Wada Y, Shimada M, Murano T, et al. A liquid biopsy assay for noninvasive identification of lymph node metastases in T1 colorectal cancer. Gastroenterol. Published online April 2, 2021. doi: 10.1053/j.gastro.2021.03.062