Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

Tao, Jianhua; Wang, Xiaotong; Yuan, Wei; Chen, Jianan; Wang, Zhijie; Ma, Yun-Bin; Zhao, Fen; Zhang, Liu-Yuan; Ma, Jie; Liu, Qian

doi:10.12998/wjcc.v10.i14.4446

Cited by 6 publications

(6 citation statements)

References 43 publications

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“…For example, OSBPL1A (oxysterol binding protein-like 1A, ReliefF weight=0.058) was the top aging marker. OSBPL1A is one of a set of intracellular lipid receptors and is closely related to lipid metabolism and cholesterol metabolism ( 32 , 33 ). TIGD4 (tigger transposable element derived 4, ReliefF weight=0.0253), as the top disease marker, was related to glycogen metabolism.…”

Section: Resultsmentioning

confidence: 99%

The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level

Chen,

Yao,

Zhao

et al. 2023

Front. Endocrinol.

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BackgroundType 2 diabetes mellitus (T2DM) is a chronic endocrine metabolic disease caused by insulin dysregulation. Studies have shown that aging-related oxidative stress (as “oxidative aging”) play a critical role in the onset and progression of T2DM, by leading to an energy metabolism imbalance. However, the precise mechanisms through which oxidative aging lead to T2DM are yet to be fully comprehended. Thus, it is urgent to integrate the underlying mechanisms between oxidative aging and T2DM, where meaningful prediction models based on relative profiles are needed.MethodsFirst, machine learning was used to build the aging model and disease model. Next, an integrated oxidative aging model was employed to identify crucial oxidative aging risk factors. Finally, a series of bioinformatic analyses (including network, enrichment, sensitivity, and pan-cancer analyses) were used to explore potential mechanisms underlying oxidative aging and T2DM.ResultsThe study revealed a close relationship between oxidative aging and T2DM. Our results indicate that nutritional metabolism, inflammation response, mitochondrial function, and protein homeostasis are key factors involved in the interplay between oxidative aging and T2DM, even indicating key indices across different cancer types. Therefore, various risk factors in T2DM were integrated, and the theories of oxi-inflamm-aging and cellular senescence were also confirmed.ConclusionIn sum, our study successfully integrated the underlying mechanisms linking oxidative aging and T2DM through a series of computational methodologies.

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Section: Resultsmentioning

confidence: 99%

The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level

Chen,

Yao,

Zhao

et al. 2023

Front. Endocrinol.

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“…Low HDL levels in CRC patients may be caused by malnutrition in tumor patients or by the tumor affecting lipid metabolism, resulting in lower HDL levels. Literature reports have shown that serum HDL levels correlate with tumor size and stage of CRC, which further suggested that HDL levels may be associated with the severity and prognosis of CRC 25 . In addition, a team investigation also found that elevated TG/HDL‐C ratio was also associated with an increased risk of CRC in adults in northern China 26 .…”

Section: Discussionmentioning

confidence: 92%

“…Literature reports have shown that serum HDL levels correlate with tumor size and stage of CRC, which further suggested that HDL levels may be associated with the severity and prognosis of CRC. 25 In addition, a team investigation also found that elevated TG/HDL‐C ratio was also associated with an increased risk of CRC in adults in northern China. 26 Assessing HDL levels alone in patients with CRC does not necessarily provide diagnostic or predictive value.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR‐1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer

Wu,

Zhang,

Lin

et al. 2024

Cancer Medicine

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BackgroundIn recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC.MethodsWe screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR‐1470 in healthy volunteers and CRC patients were analyzed using qRT‐PCR. To evaluate the diagnostic potential of the selected miR‐1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR‐1470 in CRC cell lines, we detected the miR‐1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR‐1470 in SW480, HCT‐116 cells.ResultsExosomal miR‐1470 exhibited significant up‐regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876–0.7920) for exosomal miR‐1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR‐1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR‐1470 in CRC cell lines. CCK8 proliferation assay showed that miR‐1470 promoted the proliferation ability of SW480 and HCT‐116 cells. Transwell assay showed that miR‐1470 promoted the migration and invasion ability of SW480 and HCT‐116 cells.ConclusionThis suggested that non‐invasive diagnosis of CRC is possible by detecting the level of miR‐1470 in exosomes, which has important implications for early detection and treatment of this disease.

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“…OSBPL1A is a molecule that mediates cholesterol metabolism. Current research on OSBPL1A is limited, but existing studies suggest that it influences the production of HDL-C in the liver and intestines in conjunction with ABCA1 and also acts as a crucial prognostic factor in colorectal cancer [ 43 , 44 ]. The PRKD1 gene encodes a protein known as protein kinase D1 (PRKD1), which belongs to a significant class of signal transduction protein kinases.…”

Section: Discussionmentioning

confidence: 99%

Lipid Metabolism-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Advanced Gastric Cancer

He,

Ye,

Zhu

et al. 2024

Gastroenterology Research and Practice

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Objective. Abnormal lipid metabolism is known to influence the malignant behavior of gastric cancer. However, the underlying mechanism remains elusive. In this study, we comprehensively analyzed the biological significance of genes involved in lipid metabolism in advanced gastric cancer (AGC). Methods. We obtained gene expression profiles from The Cancer Genome Atlas (TCGA) database for early and advanced gastric cancer samples and performed differential expression analysis to identify specific lipid metabolism-related genes in AGC. We then used consensus cluster analysis to classify AGC patients into molecular subtypes based on lipid metabolism and constructed a diagnostic model using least absolute shrinkage and selection operator- (LASSO-) Cox regression analysis and Gene Set Enrichment Analysis (GSEA). We evaluated the discriminative ability and clinical significance of the model using the Kaplan-Meier (KM) curve, ROC curve, DCA curve, and nomogram. We also estimated immune levels based on immune microenvironment expression, immune checkpoints, and immune cell infiltration and obtained hub genes by weighted gene co-expression network analysis (WGCNA) of differential genes from the two molecular subtypes. Results. We identified 6 lipid metabolism genes that were associated with the prognosis of AGC and used consistent clustering to classify AGC patients into two subgroups with significantly different overall survival and immune microenvironment. Our risk model successfully classified patients in the training and validation sets into high-risk and low-risk groups. The high-risk score predicted poor prognosis and indicated low degree of immune infiltration. Subgroup analysis showed that the risk model was an independent predictor of prognosis in AGC. Furthermore, our results indicated that most chemotherapeutic agents are more effective for AGC patients in the low-risk group than in the high-risk group, and risk scores for AGC are strongly correlated with drug sensitivity. Finally, we performed qRT-PCR experiments to verify the relevant results. Conclusion. Our findings suggest that lipid metabolism-related genes play an important role in predicting the prognosis of AGC and regulating immune invasion. These results have important implications for the development of targeted therapies for AGC patients.

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Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

Cited by 6 publications

References 43 publications

The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level

The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level

Exosomal miR‐1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer

Lipid Metabolism-Related Gene Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Advanced Gastric Cancer

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