Clustering of patients with intrahepatic cholangiocarcinoma based on serum periostin may be predictive of prognosis

Thuwajit, Chanitra; Thuwajit, Peti; Jamjantra, Pranisa; Pairojkul, Chawalit; Wongkham, Sopit; Bhudhisawasdi, Vajarabhongsa; Ono, Junya; Fujimoto, Kiminori; Izuhara, Kenji

doi:10.3892/ol.2017.6250

Cited by 19 publications

(27 citation statements)

References 62 publications

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“…Our results demonstrating a strong positive correlation between increasing levels of both tumor and serum Postn as a function of increasing liver cholangiocarcinoma tumor size, enhanced desmoplastic stroma, and increased gross peritoneal metastases in BDEneu tumor‐bearing rats also strongly support stromal Postn overexpression as being predictive of progressive cholangiocarcinoma growth in our rat cholangiocarcinoma model. Our findings are thus compatible with the findings of Utispan et al6 and Thuwajit et al11 for human ICC. In contrast, rats with biliary cirrhosis induced by bile duct ligation were previously demonstrated by us not to exhibit measurable levels of Postn protein expression by either immunohistochemistry or western blot analysis 1…”

Section: Discussionsupporting

confidence: 94%

“…Patients with cholangiocarcinoma were also reported to exhibit a significantly higher median Postn level in their serum than those with normal liver, liver cirrhosis, HCC, or other malignancies 10. High serum and tumor tissue samples with high Postn expression detected by immunohistochemistry have been significantly associated with reduced survival in patients with ICC,11 which suggests that elevated serum Postn may be used to divide such patients into low and high Postn groups.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

Manzanares

Campbell

Maldonado

et al. 2017

Hepatology Communications

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Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three‐dimensional culture models of rat cholangiocarcinoma progression. Using our orthotopic model, we demonstrated a strong positive correlation between tumor and serum periostin and mesothelin and increasing liver tumor mass and associated peritoneal metastases that also reflected differences in cholangiocarcinoma cell aggressiveness and malignant grade. Periostin immunostaining was most prominent in the desmoplastic stroma of larger sized more aggressive liver tumors and peritoneal metastases. In comparison, mesothelin was more highly expressed in the cholangiocarcinoma cells; the slower growing more highly differentiated liver tumors exhibited a luminal cancer cell surface immunostaining for this biomarker, and the rapidly growing less differentiated liver and metastatic tumor masses largely showed cytoplasmic mesothelin immunoreactivity. Two molecular weight forms of mesothelin were identified, one at ∼40 kDa and the other, a more heavily glycosylated form, at ∼50 kDa. Increased expression of the 40‐kDa mesothelin over that of the 50 kDa form predicted increased malignant progression in both the orthotopic liver tumors and in cholangiocarcinoma cells of different malignant potential in three‐dimensional culture. Moreover, coculturing of cancer‐associated myofibroblasts with cholangiocarcinoma cells promoted overexpression of the 40‐kDa mesothelin, which correlated with enhanced malignant progression in vitro. Conclusion: Periostin and mesothelin are useful predictors of tumor progression in our rat desmoplastic cholangiocarcinoma models. This supports their relevance to human intrahepatic cholangiocarcinoma. (Hepatology Communications 2018;2:155–172)

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

Manzanares

Campbell

Maldonado

et al. 2017

Hepatology Communications

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“…In a recent study, similar results were observed. Thus, serum POSTN levels in patients with cholangiocarcinoma were significantly increased compared with that in healthy controls, patients with benign liver diseases, and even patients with breast cancer, indicating that serum POSTN levels could be used as a diagnostic biomarker ( 96 ). Furthermore, high levels of serum POSTN, as well as tissue POSTN levels, were significantly associated with reduced survival rate.…”

Section: Serum Postn Levels As a Biomarker Of Poor Prognosismentioning

confidence: 99%

“…Furthermore, high levels of serum POSTN, as well as tissue POSTN levels, were significantly associated with reduced survival rate. Serum POSTN was identified as an independent prognostic factor suggesting that it could be used as a marker of poor prognosis in patients with cholangiocarcinoma ( 96 ).…”

Section: Serum Postn Levels As a Biomarker Of Poor Prognosismentioning

confidence: 99%

Periostin: A Matricellular Protein With Multiple Functions in Cancer Development and Progression

2018

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Tumor microenvironment is considered nowadays as one of the main players in cancer development and progression. Tumor microenvironment is highly complex and consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial cells, or infiltrating leukocytes) and a large list of extracellular matrix proteins and soluble factors. The way that microenvironment components interact among them and with the tumor cells is very complex and only partially understood. However, it is now clear that these interactions govern and modulate many of the cancer hallmarks such as cell proliferation, the resistance to death, the differentiation state of tumor cells, their ability to migrate and metastasize, and the immune response against tumor cells. One of the microenvironment components that have emerged in the last years with strength is a heterogeneous group of multifaceted proteins grouped under the name of matricellular proteins. Matricellular proteins are a family of non-structural matrix proteins that regulate a variety of biological processes in normal and pathological situations. Many components of this family such as periostin (POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to regulate key aspect of tumor biology, including proliferation, invasion, matrix remodeling, and dissemination to pre-metastatic niches in distant organs. Matricellular proteins can be produced by tumor cells themselves or by tumor-associated cells, and their synthesis can be affected by intrinsic and/or extrinsic tumor cell factors. In this review, we will focus on the role of POSTN in the development and progression of cancer. We will describe their functions in normal tissues and the mechanisms involved in their regulation. We will analyze the tumors in which their expression is altered and their usefulness as a biomarker of tumor progression. Finally, we will speculate about future directions for research and therapeutic approaches targeting POSTN.

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“…Thus, these two independent interaction-induced signaling pathways are important for the development and maintenance of cancer cells [ 40 ]. Elevated levels of POSTN have been detected in sera from patients with various types of cancers [ 45 , 46 , 47 ], suggesting that POSTN may be a useful biomarker for those cancers. The detection of POSTN by the immunohistochemical (IHC) staining of tumor lesions by anti-POSTN mAbs targeting the fasciclin domain, which can inhibit integrin-mediated cell migration in vitro, has also been reported [ 48 ].…”

Section: Current Knowledge Regarding the Roles Of The Matricellulamentioning

confidence: 99%

The Roles of Matricellular Proteins in Oncogenic Virus-Induced Cancers and Their Potential Utilities as Therapeutic Targets

Maeda

Maenaka

2017

IJMS

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Matricellular proteins differ from other classical extracellular matrix proteins; for instance, they are transiently expressed as soluble proteins rather than being constitutively expressed in pathological conditions, such as acute viral infections. Accumulating studies have revealed that matricellular proteins, including osteopontin and tenascin-C, both of which interact with integrin heterodimers, are involved in inflammatory diseases, autoimmune disorders, and cancers. The concentrations of these matricellular proteins are elevated in the plasma of patients with certain types of cancers, indicating that they play important roles in oncogenesis. Chronic viral infections are associated with certain cancers, which are distinct from non-viral cancers. Viral oncogenes play critical roles in the development and progression of such cancers. It is vital to investigate the mechanisms of tumorigenesis and, particularly, the mechanism by which viral proteins induce tumor progression. Viral proteins have been shown to influence not only the viral-infected cancer cells, but also the stromal cells and matricellular proteins that constitute the extracellular matrix that surrounds tumor tissues. In this review, we summarize the recent progress on the involvement of matricellular proteins in oncogenic virus-induced cancers to elucidate the mechanism of oncogenesis and consider the possible role of matricellular proteins as therapeutic targets in virus-induced cancers.

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Clustering of patients with intrahepatic cholangiocarcinoma based on serum periostin may be predictive of prognosis

Cited by 19 publications

References 62 publications

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

Periostin: A Matricellular Protein With Multiple Functions in Cancer Development and Progression

The Roles of Matricellular Proteins in Oncogenic Virus-Induced Cancers and Their Potential Utilities as Therapeutic Targets

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