New Evidence for Liquid Biopsy Early Screening: Geneseeq MERCURY Achieves 0.95 AUC in Preoperative Differentiation of Kidney Masses

A new blood-based test shows promise in distinguishing benign from malignant kidney masses before surgery, potentially helping doctors avoid unnecessary procedures on harmless growths while catching cancers early.

The technology, developed by Chinese diagnostics company Geneseeq, analyzes fragments of tumor DNA circulating in the bloodstream. In a study of 488 patients published in the journal Molecular Biomedicine, the test achieved an accuracy rate of 94.6% in distinguishing cancerous kidney masses from benign lesions.

The findings address a persistent challenge in urology: determining whether a kidney mass is cancerous before surgery. Benign growths such as fat-poor angiomyolipomas and oncocytomas often mimic kidney cancer on imaging scans, leading to difficult decisions about whether to remove the kidney or preserve it.

"Over-treatment of benign lesions can increase surgical risks and affect long-term kidney function, while underestimating malignant lesions may delay intervention," the researchers wrote. The study was led by Professor Wang Yongquan at the First Affiliated Hospital of the Army Medical University in Chongqing, China.

A Multi-Layered Approach

Geneseeq's MERCURY technology takes a comprehensive approach to detecting cancer signals in blood. Rather than looking for a single biomarker, the test analyzes three types of information from cell-free DNA fragments: copy number variations, methylation patterns inferred from fragment characteristics, and nucleosome footprints.

The researchers sequenced plasma DNA at an average depth of five times across the entire genome, then used machine learning to integrate the three data types into a single predictive model. The training cohort included 331 patients—171 with kidney cancer and 160 with benign lesions—while a separate validation cohort of 144 patients tested the model's accuracy.

The integrated model achieved a sensitivity of 89% and specificity of 87% in the validation set. When researchers restricted the analysis to the most challenging cases—solid lesions like angiomyolipomas and oncocytomas that are hardest to distinguish from cancer on imaging—the accuracy remained high at 95.9%.

Performance in Difficult Cases

Kidney cancer presents a particular challenge for liquid biopsy because these tumors tend to shed relatively little DNA into the bloodstream. In this study, nearly 90% of kidney cancer samples had tumor fractions below 3%, yet the model maintained strong performance in this subgroup with an accuracy of 94.1%.

The test also showed promise across different tumor sizes. For masses larger than 4 centimeters, it correctly identified 85.3% of benign lesions. For smaller masses of 4 centimeters or less, it detected 84.6% of cancers. Early-stage kidney cancers were identified with sensitivities of 77% for stage I and 100% for stage II.

Perhaps most notably, the model correctly classified all 35 cases in the study where imaging results disagreed with the final pathology diagnosis. In a separate exploration cohort of 13 renal oncocytomas—tumors that frequently lead to unnecessary surgery—the test correctly identified 12 as benign, achieving a specificity of approximately 92%.

Building on Previous Work

This study, called DECIPHER-RCC-2, follows earlier research by the same team that explored kidney cancer early detection using the same MERCURY platform. That work was published in ESMO Open in June 2025.

Geneseeq, based in Nanjing, has been expanding its liquid biopsy capabilities across multiple cancer types. The company's DECIPHER series has published early detection results for colorectal, liver, lung, gastric, endometrial, esophageal, breast, pancreatic, prostate, ovarian, and biliary tract cancers in peer-reviewed journals over the past five years.

The company's broader portfolio includes diagnostic kits approved by regulatory authorities in China and the United States. In 2025, Geneseeq received FDA approval for a comprehensive next-generation sequencing panel for solid tumors, making it the first company to achieve regulatory clearance in China, the U.S., and Europe for such a test.

The latest kidney mass differentiation study adds to growing evidence that multi-omics liquid biopsy approaches can provide clinically useful information even when tumors release minimal DNA into the bloodstream. If validated in larger, prospective trials, the test could help urologists make more informed decisions about surgery, potentially sparing patients with benign growths from unnecessary procedures while ensuring those with cancer receive timely treatment.

The study was published in Molecular Biomedicine with the DOI: 10.1186/s43556-026-00568-4. The journal has an impact factor of 13.