Identification of cystatin SN as a novel biomarker for pancreatic cancer

Jiang, Jie; Liu, Huiling; Liu, Zhihao; Tan, Siwei; Wu, Bin

doi:10.1007/s13277-014-3033-3

Cited by 50 publications

(46 citation statements)

References 26 publications

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“…In accordance with this, the Kaplan–Meier survival analysis demonstrated that the OS and DFS of breast cancer patients with high CST1 expression were worse than those with low CST1 expression. High CST1 expression was also reported by previous studies to be linked to poor survival in colorectal cancer [40], pancreatic cancer [41], and non-small cell lung cancer patients [42], which was consistent with our results. Interestingly, the prognostic effect of CST1 is especially strong in stratified survival analysis of breast cancer, according to the factors attributed to worse outcome.…”

Section: Discussionsupporting

confidence: 93%

Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

Dai

Chen

et al. 2017

J Mol Med

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Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer.Key messages High CST1 expression is negatively correlated with survival of breast cancer patients.CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells.CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer. Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-017-1537-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

Dai

Chen

et al. 2017

J Mol Med

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“…For instance, we screened 98 DEGs which were observed in all the pancreatic cancer samples analyzed. Of these DEGs, some were previously recognized regulators associated with this malignancy, such as S100P [18], ITGA3 [19], ITGA2 [20], LAMC2 [21], SERPINB5 [22], SDC1 [23] and CST1 [24], some were identified involved in this disease for the first time (Table 1). Further validation of genes with altered expression was based on data from a different platform, which was of benefits in terms of evading platform-specific biases.…”

Section: Discussionmentioning

confidence: 99%

Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer

et al. 2017

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Pancreatic cancer is a complex and heterogeneous disease with the etiology largely unknown. The deadly nature of pancreatic cancer, with an extremely low 5-year survival rate, renders urgent a better understanding of the molecular events underlying it. The aim of this study is to investigate the gene expression module of pancreatic adenocarcinoma and to identify differentially expressed genes (DEGs) with prognostic potentials. Transcriptome microarray data of five GEO datasets (GSE15471, GSE16515, GSE18670, GSE32676, GSE71989), including 117 primary tumor samples and 73 normal pancreatic tissue samples, were utilized to identify DEGs. The five sets of DEGs had an overlapping subset consisting of 98 genes (90 up-regulated and 8 down-regulated), which were probably common to pancreatic cancer. Gene ontology (GO) analysis of the 98 DEGs showed that cell cycle and cell adhesion were the major enriched processes, and extracellular matrix (ECM)-receptor interaction and p53 signaling pathway were the most enriched pathways according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Elevated expression of gap junction protein beta 2 (GJB2) and reduced endoplasmic reticulum oxidoreductase 1-like beta (ERO1LB) expression were validated in an independent cohort. Kaplan-Meier survival analysis revealed that GJB2 and ERO1LB levels were significantly associated with the overall survival of pancreatic cancer patients. GJB2 and ERO1LB are implicated in pancreatic cancer progression and can be used to predict patient survival. Therapeutic strategies targeting GJB2 and facilitating ERO1LB expression may deserve evaluation to improve prognosis of pancreatic cancer patients.

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“…33, 34, 35 Paradoxically, CST1 has been proposed to be a novel marker in several tumors, including non-small cell lung cancer, pancreatic cancer, colorectal cancer and gastric cancer. 8, 9, 10, 11 The upregulated expression of CST1 is associated with proliferation, invasion and metastasis of cells, which are the main characteristics of tumor malignancy. 8, 10, 36 To date, the cooperative effect of CatB and CST1 during tumorigenesis remains poorly defined.…”

Section: Discussionmentioning

confidence: 99%

“…7 Cystatin SN (CST1), encoded by CST1, is a member of the type 2 cystatin family, and the induction of CST1 expression is associated with tumorigenesis, increased cancer cell proliferation and invasion, and tumor recurrence. 8, 9, 10, 11 As CatB is a functional protease and CST1 is its inhibitor, it is highly paradoxical that both of them contribute to tumorigenesis. To date, the underlying relationship between CST1 and CatB, and their roles in tumor development, remains poorly understood.…”

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confidence: 99%

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation

Park

Lee

et al. 2017

Cell Death Dis

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Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.

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Identification of cystatin SN as a novel biomarker for pancreatic cancer

Cited by 50 publications

References 26 publications

Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

Genome-scale analysis identifies GJB2 and ERO1LB as prognosis markers in patients with pancreatic cancer

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation

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