Affiliated Hospital of Nantong University Seeks Technology Transfer of a Novel circRNA Biomarker for Non-Small Cell Lung Cancer Diagnosis

Recently, the Affiliated Hospital of Nantong University released a public notice on the transformation of scientific and technological achievements in accordance with the Law of the People's Republic of China on Promoting the Transformation of Scientific and Technological Achievements, proposing to transfer an invention patent it owns.“A circRNA Biomarker for Non-Small Cell Lung Cancer Screening”, transferred to the industrial party, with a transfer amount of RMB20,000 yuan. This patented technology was developed by experts in the field of laboratory medicine at the Affiliated Hospital of Nantong UniversityJu Shaoqing and his teamCompleted.

The patent invention proposed for conversion in this project provides a novel circular RNA (circRNA) molecular biomarker for non-small cell lung cancer screening. This biomarker is specifically highly expressed in the serum of lung cancer patients and is closely associated with disease progression. Validated through large-scale clinical studies, it demonstrates excellent diagnostic performance in distinguishing lung cancer patients from healthy individuals, with an area under the curve (AUC) reaching0.810, providing a promising novel molecular detection method for early non-invasive screening of lung cancer.

Lung cancer is currently the malignant tumor with the highest incidence and mortality rates worldwide. Among them,Non-Small Cell Lung CancerIt is the most common type of primary lung cancer, accounting for approximately 85% of all lung cancers, with its main subtypes includingLung AdenocarcinomaandSquamous Cell Lung Carcinoma。

Despite advances in multidisciplinary comprehensive treatment for lung cancer, a large number of patients are diagnosed at intermediate or advanced stages due to the insidious nature of early symptoms, the limited population coverage of conventional imaging examinations (such as low-dose spiral CT), and the lack of highly sensitive early molecular diagnostic tools. This has directly resulted in persistently low overall survival rates among lung cancer patients. Therefore,Development of Effective Early Screening and Diagnostic Methods, is a key measure to reduce lung cancer mortality.

In the field of molecular diagnostics,Circular RNAIn recent years, it has attracted widespread attention. It is a special type of non-coding RNA molecule with a closed-loop structure, lacking the 5' cap and 3' polyadenylated tail characteristic of traditional linear RNAs. This unique circular structure confers resistance to degradation by RNases, resulting in greater stability in vivo and enabling its detection in body fluids such as blood. Functionally, circular RNAs can act as "sponges" that sequester intracellular microRNAs (miRNAs), thereby relieving miRNA-mediated repression of their target genes. This indirectly regulates gene expression and participates in tumorigenesis and tumor progression.

With the widespread adoption of high-throughput sequencing technology, numerous studies have demonstrated that many circular RNAs exhibit differential expression between non-small cell lung cancer tissues and normal tissues, and their aberrant expression is closely associated with malignant processes such as tumor proliferation and metastasis. Therefore,Systematic identification of circular RNAs with specific dysregulation in non-small cell lung cancer,and elucidating its functions holds significant scientific value and clinical importance for the development of novel diagnostic biomarkers and therapeutic approaches.

Therefore, in the face of the significant clinical demand for early diagnosis of non-small cell lung cancer (NSCLC) and the limitations of existing methods, identifying a stable, sensitive, and easily accessible biomarker has become the key to overcoming the current challenges.

The core advantages and advanced nature of this patented technology are primarily reflected in its first-time identification and systematic validation of a novel circular RNA molecular biomarker with high diagnostic potential—hsa_circ_0016601。

This finding was not accidental but was based on rigorous high-throughput sequencing technology. By systematically comparing the circular RNA expression profiles of non-small cell lung cancer tissues with those of adjacent normal tissues, significantly differentially expressed molecules were screened out. This marks that the biomarker originates from the very source of tumorigenesis—At the level of gene transcriptionPrecisely targeted, with a solid molecular biological basis for its association with the disease.

One key advantage of this biomarker lies in itsExceptional Stability and DetectabilityBenefiting from the covalently closed circular structure of circular RNA, hsa_circ_0016601 can effectively resist degradation by RNases in vivo. Patent experimental data confirm that its detection signal remains stable even after serum samples are stored at room temperature for extended periods or subjected to repeated freeze-thaw cycles.

This characteristic is crucial for clinical laboratory testing. It implies that diagnostic assays developed using this biomarker have relatively lenient requirements for sample collection, transport, and storage conditions, making them better suited for real-world clinical applications. Furthermore, its stable presence in peripheral blood enables non-invasive “liquid biopsy” through simple venipuncture.

In terms of clinical diagnostic performance, this patentProvides a complete chain of evidence, from molecular characteristics to large-scale clinical validation. The study was validated in over 250 clinical serum samples (including 132 patients and 119 healthy controls),The expression level of hsa_circ_0016601 in the serum of patients with non-small cell lung cancer is significantly higher than that in healthy individuals.

What is more valuable,Its expression level is closely associated with the malignant progression of tumors:Higher concentrations of this biomarker are observed in patients with more advanced TNM stages (Stage III–IV), distant metastasis, or higher cellular proliferative activity (high Ki-67 expression). This suggests that it may not only serve to distinguish between diseased and healthy individuals but also provide adjunctive information for assessing tumor aggressiveness and prognosis.

The most prominent advancement of this patent is reflected in itsQuantitative Evaluation of Diagnostic PerformanceWhen hsa_circ_0016601 is used alone for diagnosis, the area under the receiver operating characteristic curve (AUC) reaches as high as 0.810. AUC is a core metric for assessing diagnostic accuracy, with values ranging from 0.5 to 1; the closer the value is to 1, the higher the diagnostic accuracy.An AUC value of 0.810 indicates that the biomarker exhibits good discriminatory ability when used alone.Meanwhile, its diagnostic sensitivity is72%, with a specificity of77%, which means it can correctly identify 72% of true patients and correctly exclude 77% of healthy individuals, with overall performance superior to that of some traditional protein-based tumor markers commonly used in clinical practice.

Furthermore, this patent explores and validates an innovative combined diagnostic strategy, thereby elevating diagnostic efficacy to new heights. When hsa_circ_0016601 was jointly analyzed with routinely measured clinical tumor markers—carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (Cyfra21-1)—the constructed diagnostic model achieved breakthrough performance.

The AUC value of the four combined factors further increased to0.879, and the diagnostic sensitivity significantly increased to86%. This means that this"Novel Circular RNA + Traditional Protein Biomarkers"combination regimen, which can capture more cases that would be missed by single indicators, providing a more powerful and reliable tool for early detection and auxiliary subtyping diagnosis of non-small cell lung cancer.

Given the biomarker’s significant superiority in diagnosing non-small cell lung cancer (NSCLC) and its potential for clinical translation, the research team did not rest on the discovery of a single target. In response to the unmet complex clinical needs in lung cancer diagnosis and treatment, relevant institutions and enterprises are systematically expanding their unique expertise and technological platforms accumulated in circular RNA research into broader translational medicine domains.

Circurna’s ciRNA™ circular RNA platform,Using proprietary cyclization and purification technologies, linear RNA molecules are ligated into covalently closed circular structures. This unique closed-loop structure endows ciRNA™ with superior stability compared to conventional linear mRNA, enabling resistance to nuclease degradation. Consequently, it achieves more sustained protein expression and may elicit a stronger immune response, which theoretically translates to fewer administrations, prolonged therapeutic duration, and reduced side effects.

To efficiently deliver circular RNA molecules to target cells, the platform integrates a heat-stable nanoparticle delivery system and is currently collaborating withGATC HealthCollaborate to leverage artificial intelligence in optimizing the design of lipid nanoparticles, targeting ligands, and payloads, thereby enhancing therapeutic precision. Currently, Circurna remains a preclinical-stage company with no products yet entered into human clinical trials.

Currently, to advance its R&D pipeline, the company has partnered withGlobal CRDMO Company: Yiming BiologyEstablished a strategic partnership, with the latter providing end-to-end services—including process development, scale-up manufacturing, and GMP production of circular RNA active pharmaceutical ingredients (APIs) and drug products—to accelerate the advancement of its candidate therapies toward first-in-human clinical trials.

Guangzhou Gese Biotechnology Co., Ltd.Provides real-time quantitative PCR detection kits for circular RNA (circRNA) and related diagnostic biomarker development services. It offers specialized kits for the precise detection of circRNA expression levels to researchers in both scientific and clinical fields, along with a comprehensive suite of solutions covering the entire workflow from biomarker discovery to validation.

Its technical mechanism involves the use of the company’s proprietary reverse transcriptase and qPCR detection system to achieve highly sensitive and specific quantitative analysis of structurally stable circular RNA molecules. To support this service, the company has established a comprehensive platform containingOver 2,000 pairsof validated specific primers"circRNA Primer Library", and independently developedcircBank: A Database of Human Circular RNAs, to facilitate the screening and development of diagnostic biomarkers.

Overall, Gisse Biotech is currently in an industrialization phase marked by a deep expansion from scientific research services into clinical applications and drug development. The company not only boasts a mature portfolio of research reagents but has also progressively established a comprehensive technical platform encompassing circRNA in vitro synthesis, process development, and GMP manufacturing. It has already begun providing critical CRO services and technical support to domestic and international research institutions and pharmaceutical companies for their circRNA vaccine and drug development projects.

In the future, with the accumulation of more clinical data and the standardization of detection technologies, circular RNAs are expected to form more comprehensive solutions in the field of precision medicine, such as early cancer screening and treatment efficacy monitoring, providing new possibilities to address the limitations of existing clinical diagnostic approaches.