CN-121978227-A - Colorectal cancer related polycyclic aromatic hydrocarbon plasma metabolism molecular biomarker and screening method and application thereof

Abstract

The invention discloses a colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarker and a screening method and application thereof, belonging to the technical field of colorectal cancer, and detecting plasma of colorectal cancer cases and healthy control group personnel by a gas chromatography mass spectrometry; the method comprises the steps of deriving a plurality of metabolite information detected by a plasma sample, adjusting a batch effect through a ComBat method based on empirical Bayes, screening polycyclic aromatic hydrocarbon with a detection rate of more than 60% in colorectal cancer case control samples, screening three polycyclic aromatic hydrocarbons as colorectal cancer related polycyclic aromatic hydrocarbon plasma metabolism molecular biomarkers by adopting a random forest method, wherein the biomarkers are combined biomarkers of fluorene, anthracene and benzo [ k ] fluoranthene, the combined AUC of the three polycyclic aromatic hydrocarbons is 0.785, and the prediction of colorectal cancer has higher accuracy.

Inventors

• WANG MEILIN
• LI SHUWEI
• GU DONGYING
• CHEN SILU
• FU ZAN
• LI ZHENGYI

Assignees

• 南京医科大学

Dates

Publication Date

20260505

Application Date

20251209

Claims (4)

1. 1. A colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarker, characterized in that the biomarker is a combination of fluorene, anthracene, benzo [ k ] fluoranthene.
2. 2. The method for screening a biomarker according to claim 1, comprising the steps of: detecting plasma of colorectal cancer group cases and healthy control group personnel by gas chromatography mass spectrometry; Deriving a plurality of metabolite information detected by the plasma sample, adjusting a batch effect by a ComBat method based on empirical Bayes, and screening out polycyclic aromatic hydrocarbon with the detection rate of more than 60% in colorectal cancer case control samples; Three polycyclic aromatic hydrocarbons are screened out by adopting a random forest method and are used as the colorectal cancer related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarkers, and the three screened polycyclic aromatic hydrocarbons are fluorene, anthracene and benzo [ k ] fluoranthene.
3. 3. The use of a biomarker according to claim 1, wherein a colorectal cancer predictive model is constructed based on the biomarker.
4. 4. Use according to claim 3, characterized in that the prediction equation of the colorectal cancer prediction model is as follows: Score = 0.035×FI + 0.445×An + 0.628×BkF + 0.019×age -0.137×sex; The value of FI is the concentration of fluorene in a plasma sample, the unit is mug/mL, the value of An is the concentration of anthracene in the plasma sample, the unit is mug/mL, the unit is BkF is the concentration of benzo [ k ] fluoranthene in the plasma sample, the unit is mug/mL, the value of age is 19-89, the value is carried out according to the actual age, the value of sex is 1 when a subject is female, and the value of sex is 2 when the subject is male; at risk scores above 1.487, the subject is at high risk of having colorectal cancer.

Description

Colorectal cancer related polycyclic aromatic hydrocarbon plasma metabolism molecular biomarker and screening method and application thereof Technical Field The invention belongs to the technical field of colorectal cancer, and particularly relates to a colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolism molecular biomarker, a screening method and application thereof. Background Colorectal cancer is one of the most common malignant tumors worldwide, and has become a serious public health problem. The occurrence of colorectal cancer is greatly affected by environmental factors, with evidence that exposure to polycyclic aromatic hydrocarbons due to poor diet significantly increases the risk of developing colorectal adenoma and colorectal cancer in individuals. Therefore, the pathogenesis factor and pathogenesis of colorectal cancer are further explored, effective environmental exposure biomarkers are searched, and the method has important public health significance for the accurate prevention and early diagnosis of colorectal cancer. At present, colorectal cancer diagnosis methods mainly rely on imaging examination, biochemical examination and pathological examination, wherein colorectal microscopy is a gold standard for colorectal cancer diagnosis and is the most effective screening method for precancerous lesions and morbidity, but the invasive nature and high operation cost limit the application of large-scale screening. In view of the advances in metabonomics analysis technology, many studies have shown the feasibility of detecting fecal metabolites as a noninvasive diagnosis of colorectal cancer. The metabonomics can reflect the metabolism of the individual under different physiological and pathological conditions by using samples such as blood plasma, urine, feces and tissues of the individual. In the prior art, researchers use non-targeted liquid chromatography-mass spectrometry (LC-MS) to detect metabolites of plasma-like varieties, find that oleic acid and iso-cholic acid play antagonism in colorectal cancer, establish 17 colorectal cancer diagnosis models of the metabolites, have better diagnosis efficacy, and also use ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to identify a group of urine metabolite markers, so that colorectal cancer patients and healthy controls can be distinguished. The novel tumor marker based on metabonomics has the characteristics of simplicity, convenience and rapidness in implementation, good individual compliance, no wound and the like, and can be widely used for screening common people. However, in the current research, biomarkers for colorectal cancer-related polycyclic aromatic hydrocarbon metabolic changes are screened against colorectal cancer incidence differences caused by polycyclic aromatic hydrocarbon exposure. Disclosure of Invention In order to overcome the problems, the invention provides a colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarker, and a screening method and application thereof. The technical scheme is as follows: In a first aspect, the invention provides a colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarker screening method, in particular to a colorectal cancer-related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarker screening method: detecting plasma of colorectal cancer group cases and healthy control group personnel by gas chromatography mass spectrometry; Deriving a plurality of metabolite information detected by the plasma sample, adjusting a batch effect by a ComBat method based on empirical Bayes, and screening out polycyclic aromatic hydrocarbon with the detection rate of more than 60% in colorectal cancer case control samples; Three polycyclic aromatic hydrocarbons are screened out by adopting a random forest method and are used as the colorectal cancer related polycyclic aromatic hydrocarbon plasma metabolic molecular biomarkers, and the three screened polycyclic aromatic hydrocarbons are fluorene, anthracene and benzo [ k ] fluoranthene. In a second aspect, the invention provides colorectal cancer-associated polycyclic aromatic hydrocarbon plasma metabolic molecular biomarkers that are combinations of fluorene, anthracene, benzo [ k ] fluoranthene. In a third aspect, the invention constructs a colorectal cancer predictive model based on the biomarkers. The prediction equation of the colorectal cancer prediction model is as follows: Score = 0.035×FI + 0.445×An + 0.628×BkF + 0.019×age - 0.137×sex; the method comprises the steps of obtaining fluorene concentration in a plasma sample in units of mug/mL, obtaining anthracene concentration in the plasma sample in units of mug/mL, obtaining benzo [ k ] fluoranthene concentration in the plasma sample in units of mug/mL by BkF, obtaining a value of age in a range of 19-89 according to actual age, obtaining a v