Clinical and prognostic significance of serum transforming growth factor-beta1 levels in patients with pancreatic ductal adenocarcinoma

Zhao, Jingjing; Liang, Yajing; Yin, Qiang; Liu, S.; Wang, Q.; Tang, Yao; Cao, Chunxiang

doi:10.1590/1414-431x20165485

Cited by 29 publications

(18 citation statements)

References 22 publications

(23 reference statements)

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“…Our previous studies have shown that TNF-α and TGF-β cytokines can upregulate ZIP14 levels in muscle cells [21]. These cytokines can be detected in the conditioned media of PDAC cell lines and sera of PDAC patients [9,[28][29][30][31][32]. It remains to be tested in future studies whether blocking TNF-α or TGF-β signaling in muscles can reduce Zip14 expression.…”

Section: Discussionmentioning

confidence: 96%

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

Shakri

Zhong

et al. 2019

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type in which the mortality rate approaches the incidence rate. More than 85% of PDAC patients experience a profound loss of muscle mass and function, known as cachexia. PDAC patients with this condition suffer from decreased tolerance to anti-cancer therapies and often succumb to premature death due to respiratory and cardiac muscle wasting. Yet, there are no approved therapies available to alleviate cachexia. We previously found that upregulation of the metal ion transporter, Zip14, and altered zinc homeostasis are critical mediators of cachexia in metastatic colon, lung, and breast cancer models. Here, we show that a similar mechanism is likely driving the development of cachexia in PDAC. In two independent experimental metastasis models generated from the murine PDAC cell lines, Pan02 and FC1242, we observed aberrant Zip14 expression and increased zinc ion levels in cachectic muscles. Moreover, in advanced PDAC patients, high levels of ZIP14 in muscles correlated with the presence of cachexia. These studies underscore the importance of altered ZIP14 function in PDAC-associated cachexia development and highlight a potential therapeutic opportunity for improving the quality of life and prolonging survival in PDAC patients.

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Section: Discussionmentioning

confidence: 96%

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

Shakri

Zhong

et al. 2019

Cancers

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“…In this study, they found that serum levels of TGF-β were significantly higher in PDAC patients than patients with benign pancreatic conditions. They also concluded that high levels of TGF-β were associated with increased tumor size, metastasis (lymphatic and distant), and higher tumor stage [ 89 ]. The five-year median overall survival was 21.7% in the low TGF-β group and 15.5% in the high TGF-β group ( p < 0.01) [ 89 ].…”

Section: Tgf-β/smad4 As a Prognostic Marker Of Pdacmentioning

confidence: 99%

The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance

Ahmed

Bradshaw

Gera

et al. 2017

JCM

140

116

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4. Among these, Smad4 mutation is relatively specific and its inactivation is found in more than 50% of invasive pancreatic adenocarcinomas. Smad4 is a member of the Smad family of signal transducers and acts as a central mediator of transforming growth factor beta (TGF-β) signaling pathways. The TGF-β signaling pathway promotes many physiological processes, including cell growth, differentiation, proliferation, fibrosis, and scar formation. It also plays a major role in the development of tumors through induction of angiogenesis and immune suppression. In this review, we will discuss the molecular mechanism of TGF-β/Smad4 signaling in the pathogenesis of pancreatic adenocarcinoma and its clinical implication, particularly potential as a prognostic factor and a therapeutic target.

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“…CD40 has also been related to transforming growth factor beta 1 (TGF-β1) [ 28 ], another key protein implicated in angiogenesis, immune suppression, and cell migration [ 30 , 31 ] and proposed as a prognostic biomarker for PC. Thus, Zhao et al [ 32 ] found higher serum TGF-β1 concentrations in patients with PC than in patients with benign pancreatic disease or healthy controls and observed a correlation of this increase with more advanced tumor stage and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Proteomic biomarkers in body fluids associated with pancreatic cancer

et al. 2018

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Pancreatic cancer (PC) is a highly malignant disease that represents the fourth leading cancer-related death worldwide. There has been very little improvement in survival rates over recent years, and surgical resection remains the only reliable curative approach. Factors that contribute to this dismal prognosis for PC include its rapid progression and invasion, the absence of specific symptoms, and the little impact of available chemotherapy. Importantly, the management of this malignancy is also limited by the lack of highly specific and sensitive biomarkers for its diagnosis and follow-up, and their identification is therefore considered a promising strategy to improve outcomes in these patients. Numerous translational studies have explored the usefulness of body fluids as a non-invasive source of PC-specific biomarkers, and innovations in proteomic methods and technologies have provided a myriad of protein biomarkers for different cancers. The adoption of a proteomic approach has improved understanding of the biology of PC and contributed to the potential identification of protein biomarkers for this disease. This review considers the most recent research efforts to develop novel proteomic biomarkers in body fluids for PC.

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Clinical and prognostic significance of serum transforming growth factor-beta1 levels in patients with pancreatic ductal adenocarcinoma

Cited by 29 publications

References 22 publications

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

The TGF-β/Smad4 Signaling Pathway in Pancreatic Carcinogenesis and Its Clinical Significance

Proteomic biomarkers in body fluids associated with pancreatic cancer

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