Blood-based Liquid Biopsy Detects Lymph Node Metastasis in Colorectal Cancer Patients

Local cancer in many parts of the body can cause lymph nodes to enlarge because of tumor cells that have metastasized into the node. Lymph node involvement is often a key factor in the diagnosis and treatment of cancer. As part of the investigations or workup for cancer, lymph nodes may be imaged or even surgically removed. Whether lymph nodes are affected will affect the staging of the cancer and overall treatment and prognosis.

Investigators at City of Hope (Duarte, CA, USA) had previously used surgically resected tissue specimens and endoscopic biopsies taken during colonoscopy to establish a panel of miRNAs and mRNAs for the identification of lymph node metastasis (LNM) in invasive submucosal colorectal cancers (T1 CRC). In the current study, they translated these tissue-based biomarkers into a noninvasive blood-based liquid biopsy assay.

The investigators analyzed 330 specimens from patients with high-risk T1 CRC, which included 188 serum samples from two clinical cohorts and matched FFPE (formalin-fixed-paraffin-embedded) samples. They performed RT-qPCR followed by logistic regression analysis to develop an integrated transcriptomic panel and establish a risk-stratification model, combined with clinical risk factors.

The liquid biopsy test was found to accurately identify lymph node metastasis with high sensitivity (83.3%) and specificity (76.2%). These results enabled the investigators to identify an optimized transcriptomic panel of four miRNAs (miR-181b, miR-193b, miR-195, miR-411) and five mRNAs (AMT, FOXA1, PIGR, MMP1, MMP9), which robustly identified patients with LNM. Application of this diagnostic model limited potential over-treatment to only 18% of all patients, which was dramatically superior to currently used models based on pathological features (92%).

"Since radical surgery dramatically reduces quality of life for patients, improving the success rate of identification of high-risk individuals with lymph node metastasis remains the challenge in T1 colorectal cancer diagnosis," said senior author Dr. Ajay Goel, chair of the department of molecular diagnostics and experimental therapeutics at City of Hope. "In the future, we hope to improve our confidence in identifying which individuals truly have lymph node metastasis via this novel biomarker-based liquid biopsy test for T1 colorectal cancer, in combination with clinical and pathological criteria. Obtaining results with more than 80% accuracy (sensitivity) in finding lymph node metastasis in the blood was a completely unexpected finding and is a complete game changer."

The blood-based liquid biopsy for detection of lymph node metastasis was described in the April 2, 2021, online edition of the journal Gastroenterology.

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