Clinicopathological significance of <i>stanniocalcin 2</i> gene expression in colorectal cancer

Ieta, Keisuke; Tanaka, Fumiaki; Yokobori, Takehiko; Kita, Yoshiaki; Haraguchi, Naotsugu; Mimori, Koshi; Kato, Hiroyuki; Asao, Takayuki; Inoue, Hiroshi; Kuwano, Hiroyuki; Mori, Masaki

doi:10.1002/ijc.24453

Cited by 57 publications

(59 citation statements)

References 37 publications

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“…STC2 has recently been described to inhibit epithelial-mesenchymal transition through the PKC/claudin-1-mediated signaling in human breast cancer cells [45]. Previous studies have shown deregulated expression of STC2 in a variety of cancers, with its expression correlating with poor prognosis [45][46][47][48][49][50][51]. Although such studies Fig.…”

Section: Discussionmentioning

confidence: 96%

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

et al. 2016

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An important role has been attributed to cancerassociated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAFsecreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometrybased proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-β1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.Electronic supplementary material The online version of this article

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Section: Discussionmentioning

confidence: 96%

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

et al. 2016

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“…In addition to a role in the cellular stress response, STC2 expression has been correlated with the development or severity of several types of cancer, including breast, prostate, renal, colorectal, and ovarian carcinomas (4,5,22,36,51). In fact, several of these studies have proposed using STC2 expression as a prognostic marker (5,15,26,36).…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, Stc1 Ϫ/Ϫ , Stc2 Ϫ/Ϫ , and Stc1 Ϫ/Ϫ Stc2 Ϫ/Ϫ mice do not exhibit any changes in serum Ca 2ϩ or phosphate levels and do not have any deficits in growth or fertility (8,9). While STC2 does not appear to play a physiologic role in the endocrine regulation of Ca 2ϩ homeostasis, numerous studies have demonstrated a link between STC2 expression and a variety of different cancers, including breast, prostate, renal, colorectal, and ovarian carcinomas (4,5,22,36,51). Other recent work has suggested that STC2 promotes invasiveness and metastasis in cancer cells (26,29,53).…”

Section: Camentioning

confidence: 99%

Stanniocalcin 2 Is a Negative Modulator of Store-Operated Calcium Entry

Zeiger

Ito

McGinley

et al. 2011

Molecular and Cellular Biology

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“…It has been reported that STC2 expression was upregulated in various tumors, including breast cancer [16,17], prostate cancer [18], esophageal squamous cell carcinoma (ESC) [19], gastric cancer [20], colorectal cancer [21], renal cell carcinoma (RCC) [22] and neuroblastoma [23]. Clinical and pathological studies reveal that STC2 overexpression correlates to advanced tumor grade, tumor invasiveness, metastasis and poor prognosis in prostate cancer, ESC, gastric cancer, colorectal cancer and RCC [18].…”

Section: Introductionmentioning

confidence: 99%

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

Shen

Guo

Wen

et al. 2014

J Exp Clin Cancer Res

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BackgroundStanniocalcin 2 (STC2) is overexpressed in several types of human cancers, and its overexpression positively correlates to tumor progression and poor prognosis. However, the clinical significance of STC2 overexpression in nasopharyngeal carcinomas (NPC) has not been investigated. This study examined STC2 expression in a cohort of 94 NPC samples, and explored its value in clinical diagnosis and prognosis.MethodsTumor samples from 94 patients diagnosed in 2008 were studied. All samples were obtained prior to treatment start. All cases were clinically diagnosed and pathologically confirmed to be poorly differentiated or undifferentiated NPC without distant metastasis, and have been treated with radical radiation therapy and followed-up for five years. Survival analyses were performed.ResultsOf the 94 NPC samples, STC2 overexpression (STC2+) was detected in 65 samples (69.1%). Overall survival rate of STC2 (+) patients is significantly lower than that of patients with normal STC2 levels (72.2% vs. 96.4%, respectively, P = 0.049). Moreover, STC2 (+) is also strongly predictive of a low progression-free survival and distant metastasis-free survival (63.0% vs 92.9%. P = 0.007; and 77.0% vs 96.4%. P = 0.028). Of the 54 patients treated with IMRT, residual tumors were found in 54.8% of STC2 positive patients (17/31), but only in 17.4% of STC2 negative ones (4/23), suggesting STC2 overexpression predicts a higher risk of residual tumors after IMRT.ConclusionsSTC2 overexpression correlates to poor prognosis for NPC and may be useful as a novel biomarker to predict NPC responses to radiation. Whether STC2 promotes NPC progression and metastasis remains to be investigated.

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Clinicopathological significance of stanniocalcin 2 gene expression in colorectal cancer

Cited by 57 publications

References 37 publications

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures

Stanniocalcin 2 Is a Negative Modulator of Store-Operated Calcium Entry

Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas

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