| Objective: Analyze the effect of cholesterol homeostasis on the occurrence and development of breast cancer by detecting the blood lipid level of serum samples and the expression of candidate genes in cholesterol homeostasis in tissue samples.Method: A total of 144 breast cancer patients who were admitted to Taizhou People’s Hospital from November 2019 to November 2020 who met the enrollment criteria were collected as the breast cancer group,collect 200 health physical examiners from outpatient clinics during the same period as a healthy control group.Their clinical data and blood lipid levels were collected to retrospectively analyze the correlation between blood lipid levels and the risk of breast cancer.A subgroup analysis was performed on the enrolled breast cancer patients to explore the relationship between comprehensive blood lipid levels and tumor clinicopathological characteristics.Collect breast cancer tissues and adjacent normal tissues from 14 of the above breast cancer patients,use these clinical samples to detect cholesterol in tissues,and use immunohistochemical staining(IHC),Quantitative Real-time PCR,Western-Blot to detect the protein location,m RNA and protein expression in human breast cancer and its corresponding adjective normal tissues of cholesterol homeostasis related genes like Low-density lipoprotein receptor(LDLR),3-hydroxy 3-methylglutaryl Coenzyme A reductase(HMGCR),Scavenger receptor Class B type 1(SCARB1),and ATP binding cassette transporter A1(ABCA1).SPSS 26.0 was used to analyze the data.The comparison between the groups was carried out by the Ftest,and the t test or non-parametric test was used for the analysis between the groups,Graph Pad Prism 8 was used for graphing.The difference in analysis results with p <0.05 between the two groups was statistically significant.Result: 1.The serum TC,TG,LDL-C,and Apo E of breast cancer patients are higher than those of the healthy control group,and the serum HDL-c and Apo A-I are lower than those of the healthy control group.There is no significant difference in Apo B levels between the two groups significance;2.Compared with breast cancer patients 55 years and older,breast cancer patients under 55 years old have lower serum TC and Apo-B levels and higher LDL-c levels;serum TG levels in menopausal breast cancer patients are significantly lower than those who have not Menopausal patients;3.By analyzing the blood lipid levels of different pathological characteristics of breast cancer patients,it was found that serum Apo A-I was elevated in estrogen receptorpositive patients,and TG was increased in patients with Ki-67 expression <15%;serum TC,TG,LDL-c and Apo B levels in patients with Luminal A breast cancer are higher,while serum LDL-C levels in patients with Luminal B breast cancer are significantly lower;the serum TC level of breast cancer with distant metastasis is reduced,and the serum TC level of patients with advanced stage(Ⅲ+Ⅳ)is lower than that of early stage(Ⅰ+Ⅱ)patients.Analysis of other subgroups was not statistically significant;4.The cholesterol level in breast cancer tissue was significantly higher than that in adjacent tissues,and the average cholesterol level in breast cancer tumors with lymph node metastasis was higher than that in those without lymph node metastasis;no significant correlation was found between cholesterol levels and other clinical indicators;5.LDLR,HMGCR,SCARB1,ABCA1 proteins are expressed in most breast cancer tissues and corresponding adjacent normal tissues;The immune response score showed that the expression of LDLR in breast cancer tissues was significantly higher than in the corresponding adjacent normal tissues.The expression of HMGCR and ABCA1 in breast cancer tissues was significantly lower than that in the corresponding adjacent tissues,while the difference between SCARB1 in breast cancer and adjacent tissues was not statistically significant;6.The m RNA expression levels of LDLR and SCARB1 in breast cancer tissues were significantly higher than those in adjacent tissues,and the m RNA expression levels of HMGCR and ABCA1 were significantly lower than those in adjacent normal tissues;the level of LDLR m RNA in hormone receptor-positive cancer tissue is lower than that in hormone receptor-negative cancer tissue,and the level of HMGCR m RNA in cancer tissue with positive lymph node is higher than that in cancer tissue with negative lymph node.No obvious correlation was found between the m RNA level of each gene and other clinical indicators;7.Western-blot results showed that the protein expression of LDLR and SCARB1 in breast cancer tissue was significantly higher than that of adjacent tissues,and the protein expression of HMGCR and ABCA1 was significantly lower than that of adjacent tissues;8.ROC curve analysis shows that ABCA1 has more diagnostic power for breast cancer.Conclusion: 1.There are certain disorders of lipid metabolism and cholesterol metabolism in breast cancer patients.2.Young women have higher levels of TC and Apo B,and lower levels of LDL-C;serum TG levels in menopausal breast cancer patients have decreased significantly.3.Serum TC,TG,Apo A-I,and Apo B levels in hormone-dependent breast cancer patients are higher than those in the healthy control group;LDL-c levels in hormone-dependent breast cancer patients are higher.4.TG is highly expressed in breast cancer patients whose Ki-67 expression is less than 15%,and the decrease of TC level can better indicate the occurrence of advanced breast cancer and distant metastasis.5.The expression of LDLR m RNA and protein is up-regulated in ER and PR-negative breast cancer tissues;the expression of HMGCR m RNA and protein is down-regulated in lymph node-negative breast cancer tissues.6.It is feasible to assist in the early diagnosis and treatment of breast cancer through ABCA1 detection,more further studying is hoped.7.For people at high risk of breast cancer,it is recommended to regularly check blood lipid levels,adjust dietary structure,and living conditions,which may have certain significance in preventing breast cancer. |
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