Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine

Ghanemi, Abdelaziz; Yoshioka, Mayumi; St‐Amand, Jonny

doi:10.3390/genes12111832

Cited by 12 publications

(9 citation statements)

References 102 publications

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“…In addition, the population selected in the dataset for clinical pathological data statistics and survival prognosis analysis may exhibit regional or genetic differences and certain differences in human physique and living environment are likely to be present. Increases in the serum levels of SPARC may occur as part of biological functions and processes such as tumors and obesity; of note, SPARC expression levels were upregulated in the lung during hypoxia induction in a mouse model, and the hypoxia-inducible factor 2A signaling pathway induces SPARC expression, which in turn has an effect on proliferation and apoptosis of tumor cells in humans (59)(60)(61). It has also been indicated that the SPARC signaling pathway induces albumin-bound paclitaxel, which enhances initial chemoresistance of patients with lung cancer and this may also be used to optimize individual gene therapy regimens, which are important for mechanistic studies, animal models and clinical treatment evaluation in NSCLC (62).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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The aim of the present study was to elucidate the significance of secreted protein acidic and cysteine rich (SPARC) expression in non-small cell lung cancer (NSCLC) in terms of clinicopathology, immune-cell infiltration and survival prognosis. A meta-analysis and bioinformatics analysis were performed using studies retrieved with PubMed, Web of Science, Wanfang Data and the Chinese National Knowledge Infrastructure databases. The meta-analysis suggested that, compared with normal tissues, SPARC expression was elevated in NSCLC tissues. The expression of SPARC was not significantly associated with TNM stage and lymph-node metastasis, and was positively associated with patient gender. Regarding the differential expression of SPARC and the relationship between expression levels and survival, the Oncomine database was consulted and Kaplan-Meier curves were drawn. It was indicated that SPARC mRNA expression levels were higher in NSCLC tissues than in normal tissues. Low expression of SPARC mRNA was negatively associated with overall survival, first progression survival and post-progression survival of patients. Further exploration of the relationship between SPARC expression and survival by univariate analysis indicated that TNM stage, lymph node metastasis, distant metastasis and depth of infiltration of lung cancer were negatively associated with patient prognosis. Cox multifactorial analysis suggested that SPARC expression levels and TNM stage were risk factors significantly affecting the prognosis of patients with NSCLC. Analysis with the GEPIA and UALCAN databases further indicated that the mRNA expression level of SPARC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was higher than that in normal lung tissue, and the SPARC expression levels were affected by factors such as the TNM stage of lung cancer.A lower the level of SPARC mRNA expression was associated with a better relative survival prognosis of patients. In the Human Protein Atlas database, the expression level of SPARC protein was higher in LUAD and LUSC than in normal lung tissue. In the Timer database, the expression level of SPARC was closely linked to immune cells related to the occurrence of lung cancer, and the degree of immune-cell infiltration and SPARC protein expression were closely related to the prognosis of patients with lung cancer. Immune cells were indicated to exhibit significant inhibition of DNA proliferation mutation mechanisms in lung cancer (P<0.05). In summary, SPARC expression may be used as a valuable indicator of prognosis in patients with NSCLC, which may provide new approaches for preventative treatment.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Shi

Zhang

et al. 2022

Oncol Lett

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“…These evidences add up on those of functional genomics [ 78 , 79 , 80 , 81 ] as illustrated by the secreted protein acidic and rich in cysteine (SPARC). Indeed, SPARC expression changes during obesity [ 82 ] and with ageing [ 83 ] and Sparc/SPARC represents an exercise-induced gene upon which exercise-induced muscle phenotype changes would depend [ 84 , 85 ]. In addition, SPARC is involved in diverse biological activities [ 86 ] related to those described above in the context of obesity, ageing, and exercise.…”

Section: Biological Similarities Between Ageing and Obesitymentioning

confidence: 99%

Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics

2021

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In modern societies, ageing and obesity represent medical challenges for healthcare professionals and caregivers. Obesity and ageing share common features including the related cellular and molecular pathways as well as the impacts they have as risk factors for a variety of diseases and health problems. Both of these health problems also share exercise and a healthy lifestyle as the best therapeutic options. Importantly, ageing and obesity also have common epigenetic changes (histone modification, DNA methylation, noncoding RNAs, and chromatin remodeling) that are also impacted by exercise. This suggests that epigenetic pathways are among the mechanisms via which exercise induces its benefits, including ageing and obesity improvements. Exploring these interrelations and based on the fact that both ageing and obesity represent risk factors for each other, would lead to optimizing the available therapeutic approaches towards improved obesity management and healthy ageing.

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“…SPARC serum levels also increase with exercise [9], both in humans and in mice [10]. We have suggested that the exercise-induced muscle phenotype changes are SPARC-dependent [11], and exercise-induced Sparc expression could be an indicator of the therapeutic efficacy of exercise and the response to exercise [12]. In addition, adding SPARC to C2C12 (muscle cells) increased their differentiation [13].…”

Section: Introductionmentioning

confidence: 95%

Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Leads to an Accelerated Ageing Phenotype Which Is Improved by Exercise Whereas SPARC Overexpression Mimics Exercise Effects in Mice

et al. 2022

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Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in various functions, including metabolism, tissue regeneration, and functional homeostasis. SPARC/Sparc declines with ageing but increases with exercise. We aim to verify two hypotheses: (1) SPARC deficiency leads to an ageing-like phenotype (metabolic decline, muscle loss, etc.), and (2) SPARC overexpression would mimic exercise, counteract ageing, and improve age-related changes. Our mice experiments are divided into two parts. First, we explore the consequences of Sparc knockout (KO) and compare them to the ageing effects. We also observe the effects of exercise. In the second part, we study the effects of SPARC overexpression and compare them to the exercise benefits. At the end, we make an analysis of the results to point out the analogies between Sparc KO and the ageing-like phenotype on the one hand and make comparisons between SPARC overexpression and exercise in the context of exercise counteracting ageing. The measurements were mainly related to tissue weights, adiposity, metabolism, and muscle strength. The main findings are that Sparc KO reduced glucose tolerance, muscle glucose transporter expression, and abdominal adipose tissue weight but increased glycogen content in the muscle. SPARC overexpression increased muscle strength, muscle mass, and expressions of the muscle glucose transporter and mitochondrial oxidative phosphorylation but lowered the glycemia and the adiposity, especially in males. Collectively, these findings, and the data we have previously reported, show that Sparc KO mice manifest an ageing-like phenotype, whereas SPARC overexpression and exercise generate similar benefits. The benefits are towards counteracting both the SPARC deficiency-induced ageing-like phenotype as well as reversing the age-related changes. The potential applications of these findings are to build/optimize Sparc KO-based animal models of various health conditions and, on the other hand, to develop therapies based on introducing SPARC or targeting SPARC-related pathways to mimic exercise against age-related and metabolic disorders.

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Measuring Exercise-Induced Secreted Protein Acidic and Rich in Cysteine Expression as a Molecular Tool to Optimize Personalized Medicine

Cited by 12 publications

References 102 publications

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Prognostic significance of SPARC expression in non‑small cell lung cancer: A meta‑analysis and bioinformatics analysis

Ageing and Obesity Shared Patterns: From Molecular Pathogenesis to Epigenetics

Secreted Protein Acidic and Rich in Cysteine (Sparc) KO Leads to an Accelerated Ageing Phenotype Which Is Improved by Exercise Whereas SPARC Overexpression Mimics Exercise Effects in Mice

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