CN-122012698-A - Biomarkers for predicting COPD cognitive dysfunction and uses thereof

Abstract

The invention relates to the technical field of biological medicine, and discloses a biomarker for predicting COPD cognitive dysfunction and application thereof. The present invention discovers and demonstrates for the first time that Stearic Acid (SA) in serum and its synthetic key enzyme ELOVL6 are specifically elevated in patients with cognitive dysfunction (CI) secondary to Chronic Obstructive Pulmonary Disease (COPD), and that its level is inversely correlated with the extent of cognitive impairment, with good predictive efficacy (AUC > 0.82) for COPD-CI. Based on this, the invention protects the use of serum SA and/or ELOVL6 as biomarkers for predicting the risk of CI secondary to COPD, in vitro diagnostic kits comprising detection reagents thereof, and methods for risk prediction using detection of the levels of the markers. The invention provides a brand new and reliable metabolism marker tool for early warning and intervention of CI of COPD patients, and has important clinical value and conversion prospect.

Inventors

• LI DONG
• HE BAOYU
• XING ZHENKAI
• ZHANG BIN
• ZHAO XUEZHEN
• BIE QINGLI
• WANG SHUAI

Assignees

• 济宁医学院

Dates

Publication Date

20260512

Application Date

20260225

Claims (8)

1. 1. A biomarker for predicting cognitive dysfunction in COPD, for use in the manufacture of a product for predicting or aiding in the diagnosis of a risk of secondary cognitive dysfunction in a COPD patient, characterized in that the biomarker is stearic acid or an ultralong chain fatty acid elongase 6 protein or an expression product of an ultralong chain fatty acid elongase 6 protein encoding gene.
2. 2. The biomarker for predicting cognitive dysfunction in COPD according to claim 1, wherein the product is an in vitro diagnostic reagent or kit.
3. 3. An in vitro test kit for predicting or assessing the risk of secondary cognitive dysfunction in a COPD patient, employing a biomarker for predicting cognitive dysfunction according to claim 2, comprising reagents for detecting the level of stearic acid in a serum sample from a subject or comprising reagents for detecting the level of ELOVL6 protein or mRNA thereof in a serum sample from a subject.
4. 4. An in vitro test kit for predicting or assessing the risk of secondary cognitive dysfunction in a COPD patient according to claim 3, wherein the reagents for detecting stearic acid levels comprise reagents and standards for liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry.
5. 5. An in vitro test kit for predicting or assessing the risk of secondary cognitive dysfunction in a COPD patient according to claim 3, wherein the agent for detecting the level of ELOVL6 protein is an ELISA detection agent or the agent for detecting the level of ELOVL6 mRNA is a reverse transcription-polymerase chain reaction agent.
6. 6. An in vitro test kit for predicting or assessing the risk of secondary cognitive dysfunction in a COPD patient according to claim 3, comprising both said reagents for detecting the level of stearic acid and said reagents for detecting the level of ELOVL6 protein or mRNA thereof.
7. 7. A method of predicting the risk of secondary cognitive dysfunction in a COPD patient comprising the steps of: (a) Obtaining a serum sample of a patient with COPD to be detected; (b) Detecting the expression level of stearic acid and/or ELOVL6 in the serum sample; (c) Comparing the detected expression level with a preset threshold; (d) And judging the risk level of the secondary CI of the patient with the COPD based on the comparison result, wherein the expression level of stearic acid and/or ELOVL6 is higher than a preset threshold value, so that the risk of the secondary CI is increased.
8. 8. The method of predicting the risk of secondary cognitive dysfunction in COPD patients according to claim 7, wherein the pre-set threshold is determined based on statistical analysis of stearic acid and/or ELOVL6 expression levels in serum of healthy control populations or populations of COPD patients who do not develop CI.

Description

Biomarkers for predicting COPD cognitive dysfunction and uses thereof Technical Field The invention relates to the technical field of biological medicines, in particular to a biomarker for predicting COPD cognitive dysfunction and application thereof. Background Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease characterized by persistent airflow limitation, with high global disease rates and heavy disease burden. Both clinical observations and epidemiological studies have found that the incidence of cognitive dysfunction (CI) in COPD patients is significantly higher than that of the same age healthy population, with about 20% -40% of COPD patients being associated with varying degrees of cognitive impairment, manifested as decreased memory, hypo-executive function, inattention, etc., severely affecting the quality of life, therapeutic compliance and long-term prognosis of the patient. At present, the pathogenesis of CI secondary to COPD is not completely elucidated, and the existing research is mainly focused on traditional approaches such as systemic inflammation, oxidative stress, hypoxia and the like, but lacks stable and early-warning biological markers. Clinically, doctors mainly rely on neuropsychological scales (such as Montreal cognitive assessment, moCA) for diagnosis, but scale assessment has the limitation of strong subjectivity and difficulty in finding small changes in early disease, so that intervention time is often delayed. Metabonomics can systematically reflect the overall change of endogenous small molecule metabolites of the body, and compared with traditional single inflammatory factors, the metabonomics are more stable in spectrum and can reflect long-term pathophysiological states, so that unique advantages are presented in early disease prediction and typing. In recent years, disorders of fatty acid metabolism have been found to play an important role in a variety of neurodegenerative diseases (such as Alzheimer's disease), but their role in CI associated with COPD has been rarely reported. Stearic Acid (SA) is a common saturated long chain fatty acid whose in vivo levels are regulated by the synthase ELOVL6 (ultralong chain fatty acid elongase 6). ELOVL6 catalyzes the conversion of palmitic acid (C16:0) to stearic acid (C18:0) and is a key rate-limiting enzyme in the prolonged metabolism of fatty acids. To date, no study has been conducted to link serum stearic acid and ELOVL6 levels to risk prediction of CI secondary to COPD, and no related patent or product has been developed that serves as a predictive marker. Therefore, a biomarker capable of accurately and early predicting CI risk of patients with COPD is discovered, and has urgent clinical requirements and great scientific value. Disclosure of Invention In order to solve the problems in the background art, the invention is realized by the following technical scheme: a biomarker for predicting cognitive dysfunction in COPD, the biomarker being used in the manufacture of a product for predicting or aiding in diagnosing a risk of secondary cognitive dysfunction in a COPD patient, the biomarker being stearic acid or an ultralong chain fatty acid elongase 6 protein or an expression product of an ultralong chain fatty acid elongase 6 protein encoding gene. Further, the product is an in vitro diagnostic reagent or kit. An in vitro test kit for predicting or assessing the risk of secondary cognitive dysfunction in a COPD patient comprising reagents for detecting the level of stearic acid in a serum sample of a subject or comprising reagents for detecting the level of ELOVL6 protein or mRNA thereof in a serum sample of a subject. Further, reagents for detecting stearic acid levels include reagents and standards for liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry. Further, the reagent for detecting the level of the ELOVL6 protein is an ELISA detection reagent, or the reagent for detecting the level of the ELOVL6 mRNA is a reverse transcription-polymerase chain reaction reagent. Further, the reagent for detecting stearic acid level and the reagent for detecting ELOVL6 protein or mRNA level thereof are contained at the same time. A method of predicting the risk of secondary cognitive dysfunction in a COPD patient comprising the steps of: (a) Obtaining a serum sample of a patient with COPD to be detected; (b) Detecting the expression level of stearic acid and/or ELOVL6 in the serum sample; (c) Comparing the detected expression level with a preset threshold; (d) And judging the risk level of the secondary CI of the patient with the COPD based on the comparison result, wherein the expression level of stearic acid and/or ELOVL6 is higher than a preset threshold value, so that the risk of the secondary CI is increased. Further, the preset threshold is determined based on statistical analysis of stearic acid and/or ELOVL6 expression levels in serum of healthy control populations or p