CN-122012689-A - Marker combination for thyroid nodule risk assessment and application thereof

Abstract

Marker combinations for thyroid nodule risk assessment and uses thereof. The present invention further identifies typical molecular markers of EICs including zchc 12, CDLN1 and NPC2 based on large sample multiple sets of chemical sequencing data, finding that Papillary Thyroid Carcinoma (PTC) has a common epithelial lineage origin with benign nodules and that epithelial intermediate state cells with malignant potential are found in benign nodules (EICs). These three genes are involved in proliferation and differentiation of cells, expression is significantly up-regulated in PTC, and assessment of risk of malignant lesions in thyroid benign nodules can be achieved by detecting the expression levels of the above markers in biological samples. The invention provides means for identifying benign nodules at high risk before malignant transformation occurs for the first time, realizes risk foresight, and has higher specificity and sensitivity for identifying benign nodules with malignant potential.

Inventors

• XIAO HAIPENG
• PENG SUI
• WANG FANG
• LIU YIHAO

Assignees

• 中山大学附属第一医院

Dates

Publication Date

20260512

Application Date

20260116

Claims (10)

1. 1. A marker combination for risk assessment of thyroid benign nodules, characterized in that the markers comprise CDLN a1, NPC2 and zchc 12.
2. 2. The marker combination according to claim 1, wherein the markers consist of CDLN, NPC2 and ZCCHC12.
3. Use of cdln1, NPC2 and zchc 12 for the preparation of a reagent and/or kit for detecting epithelial intermediate state cells (EIC).
4. Use of cdln1, NPC2 and zchc 12 in the preparation of a reagent and/or kit for assessing risk of thyroid nodules.
5. 5. The use of claim 4, wherein the assessing risk of benign thyroid nodules comprises distinguishing thyroid cancer from healthy people.
6. 6. The use of claim 4, wherein the assessing thyroid nodule risk comprises distinguishing between thyroid cancer and thyroid benign nodules.
7. 7. The use according to any one of claims 5-6, wherein the thyroid cancer is papillary thyroid cancer.
8. 8. A kit for detecting epithelial intermediate status cells (EIC), comprising reagents for detecting CDLN, NPC2, and zchc 12 expression levels.
9. 9. A kit for assessing risk of benign thyroid nodules, comprising reagents for detecting the expression levels of CDLN a, NPC2 and zchc 12.
10. 10. The kit according to any one of claims 8 to 9, wherein the reagents comprise reagents for determining CDLN, NPC2 and zchc 12 sequences, primers for amplifying CDLN, NPC2 and zchc 12 or reagents for detecting CDLN, NPC2 and zchc 12 protein expression levels.

Description

Marker combination for thyroid nodule risk assessment and application thereof Technical Field The invention relates to the fields of molecular diagnosis and tumor detection, in particular to a marker combination for thyroid nodule risk assessment and application thereof. Background The ultrasonic detection rate of thyroid nodules worldwide can reach 19-68%, wherein more than 85% of the thyroid nodules are benign nodules. ATA guidelines recommend a yearly ultrasound follow-up of cytologically or ultrasound-suggested benign thyroid nodules to monitor for signs of malignant transformation. The strategy mainly depends on an ultrasonic imaging characteristic evaluation system such as TI-RADS grading and the like, and risk layering is carried out on the ultrasonic imaging characteristic evaluation system according to the characteristics such as the morphology, the boundary, the echo, the calcification and the like of the nodule, so that follow-up frequency and further intervention decision are guided. However, this approach is somewhat subjective and it is difficult to identify high risk nodules with a malignant potential from a molecular level. The large thyroid nodule count not only creates heavy follow-up pressure, but also places a significant burden on the disease. The root cause is that the mechanism of whether and how thyroid nodules become cancerous is currently poorly understood. Therefore, there is a need in the clinic to establish a more accurate risk stratification strategy to address the management difficulties of large scale thyroid nodules. There is no clear conclusion about the occurrence pattern of thyroid cancer. Different from the clear continuous evolution of normal epithelium-polyp-cancer in colorectal cancer and from the direct malignant transformation of cervical cancer, esophageal squamous carcinoma and other tumors through abnormal hyperplasia of normal epithelium, the clear independent origin mode of benign lesion stage is not experienced, and the evolution process of thyroid cancer is not yet agreed at present. Papillary Thyroid Carcinoma (PTC) is a major pathological type of thyroid carcinoma accounting for 90% or more, and its origin and evolution mechanism are receiving a great deal of attention. Previous histology sequencing studies revealed distinct genomic mutation characteristics between benign nodules and PTC, supporting the independent theory of origin of PTC. Epidemiological studies, however, have shown that some benign thyroid nodules still have the potential to develop thyroid cancer, although their overall probability is less than 1%. Furthermore, with advances in molecular diagnostic techniques, researchers have observed the phenomenon of clonal expansion of Pi Ya in some benign nodules, suggesting a potential for further evolution towards malignant lesions, but so far lack of direct and powerful evidence to verify. Thus, the localization of benign nodules in thyroid carcinogenesis, and their relationship with malignant lesions, has not been fully elucidated. No molecular markers currently evaluate the risk of progression of benign nodules in the thyroid to thyroid cancer. It should be noted that PTC is a tumor with a relatively low abrupt load. In addition to the well-defined driving mutations including BRAF V600E (40-60%), RET/PTC gene fusion (10-20%) and RAS mutation (10-20%), there were very few background somatic mutations. This low mutation property places higher demands on the sensitivity of mutation detection, and also limits the resolution of traditional DNA sequencing in PTC clonal evolution tracking. In the prior art, imaging methods are often used for detection of thyroid cancer, including Magnetic Resonance Imaging (MRI), conventional CT, ultrasound, etc. (Gao Jinliang, etc., to enhance the diagnostic value of CT for thyroid cancer neck metastasis, chinese CT and journal of MRI). However, the imaging detection is usually performed by large-scale equipment, the detection cost is high, and the detection may be missed due to various factors during operation. Wang Qiqi et al, which uses the levels of serum microRNA-599 and Galectin-3 to predict metastasis of papillary thyroid cancer (Wang Qiqi et al, high-frequency ultrasound combined with serum microRNA-599 and Galectin-3 have predictive value in metastasis of cervical lymph nodes of papillary thyroid cancer, journal of modern medicine, china). However, the extraction and separation of miRNA molecules in serum is difficult, and a specific kit is usually required to complete the measurement. Any of these can provide an auxiliary prediction of metastasis of thyroid cancer by monitoring Ki67 and Survivin protein expression (any of these can provide a predictive value of thyroid cancer tissue Ki67 and Survivin protein expression for postoperative recurrence metastasis, international journal of test medicine). However, conventional methods for detecting the level of protein, such as immunohistochemistry and western bl