Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers

Zhang, Min; He, Shan

doi:10.3389/fphar.2023.1169566

Cited by 3 publications

References 55 publications

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Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple‐Negative Breast Cancer: A Comprehensive Analysis

Zhang,

Liu,

Zhang

et al. 2024

PPAR Research

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Triple‐negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator‐activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear. Integrated analysis of large published datasets from clinical cohorts and cell lines through databases has proven to be a powerful and essential approach for understanding cancer and uncovering new molecular targets. Here, we conducted a comprehensive study investigating the clinical relevance and drug modulation of the PPAR signaling pathway in TNBC, using data from The Cancer Genome Atlas (TCGA) for TNBC patients and Genomics of Drug Sensitivity in Cancer (GDSC) for TNBC cell lines, along with drug perturbation information from Connectivity Map (CMap). In the TCGA‐TNBC cohort, higher PPAR signaling activity was not associated with clinical stage, prognosis, tumor mutational burden, microsatellite instability, homologous recombination deficiency, stemness, or proliferation status. However, it was linked to older age; an elevated rate of piccolo presynaptic cytomatrix protein (PCLO) mutations; and oncogenic signal transduction involving MAPK, Ras, and PI3K‐Akt pathways. Additionally, it influenced biological pathways including fatty acid metabolism, AMPK signaling, and ferroptosis. Strikingly, higher PPAR activity appeared to promote the formation of an antitumor immune and microbial microenvironment. In the GDSC‐TNBC cells, nevertheless, it seemed to incur chemoresistance. Furthermore, we identified a batch of potential compounds that can regulate the PPAR signaling pathway. Lastly, our experimental validation demonstrated the ability of the histone deacetylase (HDAC) inhibitor chidamide to activate the PPAR signal in TNBC cells. In conclusion, the PPAR signaling pathway likely has pleiotropic biological effects in TNBC. These preliminary but interesting findings enhance our understanding of the role played by PPAR signal and provide new insights into the heterogeneity driven by it in TNBC.

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Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple‐Negative Breast Cancer: A Comprehensive Analysis

Zhang,

Liu,

Zhang

et al. 2024

PPAR Research

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Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: a cross-sectional study

Wang,

Jiang,

Yan

et al. 2024

Nutr Metab (Lond)

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Background With increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis. Methods Postmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected. Results A total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups ( P < 0.05). Pearson correlation analysis revealed that gastrointestinal symptoms ( r = -0.518, P < 0.01) was negatively correlated with BMD in postmenopausal women, while PCS ( r = 0.194, P = 0.004), MCS ( r = 0.305, P < 0.01), 25(OH)D ( r = 0.531, P < 0.01), total protein ( r = 0.324, P < 0.01), albumin ( r = 0.341, P < 0.01) and prealbumin ( r = 0.259, P < 0.01) were positively correlated with BMD. Logistic regression analysis revealed that both the gastrointestinal symptom score and serum 25(OH)D level were found to have a significant association with BMD (both P < 0.01). This association remained significant even after adjusting for age, BMI, education level, dietary habits, and exercise frequency. Conclusion Gastrointestinal symptoms and serum 25(OH)D elevel are associated with increased risk of osteoporosis in postmenopausal women and may be useful in predicting osteoporosis in postmenopausal women.

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Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: A cross-sectional study

Wang,

Jiang,

Yan

et al. 2024

Preprint

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Background With increasing age, the social and economic burdens of postmenopausal osteoporosis are steadily increasing. This study aimed to investigate the factors that influence the development of postmenopausal osteoporosis. Methods Postmenopausal women at the Affiliated Hospital of Jiangnan University from January 2023 to December 2023 were recruited for BMD examination. The patients were divided into a normal group, an osteopenia group and an osteoporosis group according to their T value. Questionnaires, including the Gastrointestinal Symptom Rating Scale and Short Form 12, were administered through face-to-face interviews. Bone turnover markers and serum protein levels of Fasting venous blood were detected. Results A total of 222 postmenopausal women met the inclusion criteria were recruited. Univariate analysis revealed statistically significant differences in age, education, BMI, supplementation with soy products, supplementation with dairy products, supplementation with other nutritional supplements, exercise frequency, gastrointestinal symptom score, quality of life, 25(OH)D, total protein, albumin and prealbumin among the three groups (P < 0.05). Pearson correlation analysis revealed that gastrointestinal symptoms (r = -0.518, P<0.01) was negatively correlated with BMD in postmenopausal women, while PCS (r= 0.194, P= 0.004), MCS (r= 0.305, P < 0.01), 25(OH)D (r= 0.531, P < 0.01), total protein (r= 0.324, P < 0.01), albumin (r= 0.341, P < 0.01) and prealbumin (r= 0.259, P < 0.01) were positively correlated with BMD. Conclusion Increasing age, low BMI, gastrointestinal disorders, decreased serum protein and 25(OH)D levels may contribute to an increased risk of postmenopausal osteoporosis. Supplementation with soy and dairy products and consistent exercise may prevent postmenopausal osteoporosis.

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Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers

Cited by 3 publications

References 55 publications

Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple‐Negative Breast Cancer: A Comprehensive Analysis

Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple‐Negative Breast Cancer: A Comprehensive Analysis

Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: a cross-sectional study

Gastrointestinal health and serum proteins are associated with BMD in postmenopausal women: A cross-sectional study

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