CN-122017243-A - 15-Hydroxy prostaglandin dehydrogenase

Abstract

The application relates to an application of a 15-hydroxy prostaglandin dehydrogenase detection reagent in preparing a lung adenocarcinoma prognosis evaluation kit. The application firstly defines 15-hydroxy prostaglandin dehydrogenase (15-PGDH) as a diagnosis/evaluation reagent for lung adenocarcinoma metastasis/prognosis, the expression level of the 15-hydroxy prostaglandin dehydrogenase is obviously related to the metastasis risk and survival outcome of patients, the application further reveals a negative regulation mechanism of tumor hypoxia microenvironment on 15-PGDH expression, obviously improves the biological rationality and clinical interpretation capability of metastasis judgment, and in addition, the application establishes the application potential of 15-PGDH as a new target for research and development of anti-lung adenocarcinoma metastasis medicaments, provides important theoretical support for developing a targeting treatment strategy, and has important conversion application value in the precise medical field.

Inventors

• LIU HAIPENG
• WANG YAXUAN
• XU JUNFANG
• JIANG XIAOFENG
• NIU QIANPING
• CHEN JIANXIA

Assignees

• 上海市肺科医院（上海市职业病防治院）

Dates

Publication Date

20260512

Application Date

20260120

Claims (5)

1. Application of a 15-hydroxy prostaglandin dehydrogenase detection reagent in preparing a lung adenocarcinoma prognosis evaluation kit.
2. The application of the detection reagent of the 15-hydroxy prostaglandin dehydrogenase in preparing a lung adenocarcinoma metastasis diagnosis kit.
3. The application of the combined detection reagent of the 15-hydroxy prostaglandin dehydrogenase and the low-oxygen microenvironment marker in preparing a lung adenocarcinoma metastasis diagnosis kit.
4. 4. The method of claim 3, wherein the low oxygen microenvironment marker comprises carbonic anhydrase 9.
5. Use of a 15-hydroxy prostaglandin dehydrogenase activator in the manufacture of a medicament for the treatment of lung adenocarcinoma metastasis.

Description

15-Hydroxy prostaglandin dehydrogenase Technical Field The present invention relates to the field of medicine, and in particular to 15-hydroxy prostaglandin dehydrogenase. Background Lung cancer is one of the most frequently occurring malignant tumors worldwide, with non-SMALL CELL lung cancer (NSCLC) accounting for about 80% of all lung cancer cases. Despite the continual improvement in existing therapies, the high mortality rate of lung cancer is still mainly due to its highly invasive and distant metastatic properties. Clinical data shows that about 15-20% of very early (T1-2 stage) lung cancer patients have undergone distant micrometastases at the time of diagnosis that are not monitored by conventional clinical means. Lung cancer metastasis is a complex biological process involving multiple steps and factors, including in situ invasion, vascular infiltration, circulatory survival, distant colonization, and proliferation. At present, the traditional treatment modes such as surgical excision, chemotherapy, radiotherapy and the like have limited control effect on lung cancer metastasis, so that the prognosis of patients with metastatic lung cancer is extremely poor. The tumor microenvironment plays a key regulatory role in the metastasis process of lung cancer, with the hypoxic microenvironment (hypoxia) being considered an important initiating factor driving malignant progression of the tumor. Areas with oxygen partial pressure significantly lower than that of normal tissues are commonly present in solid tumors due to abnormal vascular structures, vigorous metabolism and the like. The hypoxia microenvironment can promote metastasis by various mechanisms, hypoxia inducible factor-1 alpha (HIF-1 alpha) can up-regulate Vascular Endothelial Growth Factor (VEGF), matrix Metalloproteinases (MMPs) and other metastasis promoting molecules, and simultaneously, the p53 function deficiency under the hypoxia condition can enhance the anti-apoptosis capability and the metastatic potential of tumor cells. Although the association of hypoxia with tumor metastasis has been widely recognized, the molecular mechanism by which hypoxia microenvironment regulates lung cancer metastasis has not yet been fully elucidated, and therapeutic targets targeting this process remain very lacking. Prostaglandin E 2（PGE2) is a key lipid mediator in the inflammatory and oncological microenvironment, and has been shown to promote metastasis of various tumors such as lung cancer, colorectal cancer, etc. by activating EP4 receptors and their downstream PI3K/AKT, EGFR, etc. signaling pathways. PGE 2 is produced in vivo by arachidonic acid catalyzed by Cyclooxygenase (COX), the termination of its biological effect is primarily dependent on the degradation of 15-hydroxy prostaglandin dehydrogenase (15-PGDH, encoded by the HPGD gene), which converts PGE 2 into 15-keto-PGE 2, which has significantly reduced biological activity. However, the expression changes of 15-PGDH and its clinical significance in the course of lung cancer metastasis are not clear, and the interaction mechanism with hypoxia microenvironment is still yet to be explored. In the prior art, prognosis for non-small cell lung cancer metastasis mainly depends on TNM staging, imaging examination and traditional tumor markers (such as CEA, CYFRA21-1 and the like), but these methods have insufficient sensitivity and specificity in early stage metastasis risk prediction and personalized prognosis evaluation. In particular, the major subtype of NSCLC, lung adenocarcinoma, is currently lacking in agents that can efficiently predict metastasis progression, resulting in clinical difficulties in effective intervention in early stages of the disease, missing the optimal therapeutic window. Therefore, there is a need in the art to develop novel and reliable lung cancer metastasis prognosis kits (kits) and to build molecular mechanism-based assessment systems to improve the accurate diagnosis and survival outcome of lung cancer patients. Disclosure of Invention The invention aims to overcome the defects of the prior art, and adopts the following technical scheme: The first aspect of the invention provides the use of a 15-hydroxy prostaglandin dehydrogenase detection reagent in the preparation of a lung adenocarcinoma prognostic evaluation kit. In a second aspect, the present invention provides the use of a 15-hydroxy prostaglandin dehydrogenase assay reagent in the preparation of a diagnostic kit for lung adenocarcinoma metastasis. The third aspect of the invention provides the application of the combined detection reagent of 15-hydroxy prostaglandin dehydrogenase and the hypoxia microenvironment marker in preparing a lung adenocarcinoma metastasis diagnosis kit. Preferably, the low oxygen microenvironment marker comprises carbonic anhydrase 9. In a fourth aspect, the present invention provides the use of a 15-hydroxy prostaglandin dehydrogenase activator in the manufacture of a medicament fo