SPARC gene variants predict clinical outcome in locally advanced and metastatic pancreatic cancer patients

Arqueros, Cristina; Salazar, Juliana; Arranz, Maria; Sebio, Ana; Móra, Josefina; Sullivan, Ivana; Tobeña, M.; Martı́n-Richard, Marta; Barnadas, Agustí; Baiget, Montserrat; Páez, David

doi:10.1007/s12032-017-0993-3

Cited by 8 publications

(8 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, elevated SPARC expression at the stoma is present in approximately 40% of patients with PDAC having received resection surgery, and critically, SPARC levels appear to be an independent prognostic factor [ 44 ]. A previous study also indicated that polymorphisms in SPARC could predict outcomes for patients with locally advanced and metastatic pancreatic cancer [ 45 ]. In another study, SPARC had a dual functional role as a prognosis predictor and potential marker for lymph node metastasis in patients with resected lesions [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

Luan

Zhang

et al. 2022

BMC Cancer

View full text Add to dashboard Cite

Background Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown. Methods We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein–protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER). Results In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes. Conclusions Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes.

show abstract

Section: Discussionmentioning

confidence: 99%

The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

Luan

Zhang

et al. 2022

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…SPARC encodes an extracellular protein that plays key roles in various cancer cell processes, such as cell proliferation, migration, matrix cell adhesion, angiogenesis and tissue remodeling ( 17 ). A number of studies have identified the impact of SPARC overexpression in patients with certain types of tumor and indicated that high expression levels of SPARC were associated with poor outcome, such as in pancreatic cancer ( 18 ). Furthermore, SPARC can activate the PI3K pathway and promote oral squamous cell carcinoma proliferation and metastasis ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes in peripheral blood mononuclear cells for the diagnosis of hepatocellular carcinoma using a weighted gene co‑expression network analysis

Zeng

Shen

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Human hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive tract that is prevalent worldwide. Improving diagnosis methods for HCC helps to improve patient survival rate. The present study aimed to identify novel HCC biomarkers for the diagnosis of HCC through analyzing gene changes on peripheral blood mononuclear cells (PBMCs) and verifying these in additional samples. The gene expression profiles GSE49515 (including 10 specimens from normal patients and 10 specimens from patients with HCC) and GSE58208 (including 5 specimens from normal patients and 10 specimens from patients with HCC) were downloaded from the online Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) in PBMCs between healthy controls and patients with HCC were identified using R software. A total of 935 DEGs, including 686 upregulated DEGs and 249 downregulated DEGs, were identified in the present study. In order to identify any internal associations, these DEGs were used to construct weighted gene co-expression networks (WGCNA). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of genes in each module were conducted using the online database DAVID. Furthermore, hub genes with high module membership were identified in a co-expression network and receiver operating characteristic curves were used to verify the diagnostic values of these eight hub genes. Furthermore, the expression and diagnosis value of the eight hub genes were also verified in additional samples. The results of the present study suggested that secreted protein acidic and cysteine rich(SPARC), transmembrane protein 40 (TMEM40), solute carrier family 25 member 44, formyl peptide receptor 2 (FPR2), complement C8 β chain, N-myristoyltransferase 1, protein kinase C δ(PRKCD) and protein phosphatase, Mg 2+ /Mn 2+ dependent 1M(PPM1M) were hub genes. SPARC, TMEM40, FPR2, PRKCD and PPM1M had prominent diagnostic value according to the results from the GEO data and the additional samples. The present study demonstrated that these hub genes may help to improve the diagnosis of HCC.

show abstract

“…The SPARC protein modulates different cell functions, such as adhesion, proliferation, angiogenesis, and cell survival, and has been associated with tumor development and progression . The SPARC gene is differentially expressed in different types of cancer, as higher levels were observed in malignant tumors, such as breast, esophagus, stomach, brain, prostate, pancreas, glioma, and melanoma, and data suggest that higher expression is correlated with a more aggressive phenotype such as tumor size, metastasis, and poor prognosis …”

Section: Discussionmentioning

confidence: 99%

“…14,15 The SPARC gene is differentially expressed in different types of cancer, as higher levels were observed in malignant tumors, such as breast, esophagus, stomach, brain, prostate, pancreas, glioma, and melanoma, [16][17][18][19] and data suggest that higher expression is correlated with a more aggressive phenotype such as tumor size, metastasis, and poor prognosis. 16,17,[19][20][21][22][23][24][25] With the aim of further investigating the genetic component that can account for HCC susceptibility, we analyzed the expression patterns of SNPs in the SPARC gene in a group of HCC patients and controls to evaluate their impact on the susceptibility and survival of these patients.…”

Section: Discussionmentioning

confidence: 99%

Secreted protein acidic and rich in cysteine gene variants: Impact on susceptibility and survival of hepatocellular carcinoma patients

Darweesh

Alziz

Omar

et al. 2018

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients. Methods We conducted a case–control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real‐time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood. Results One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups. Conclusions The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides.

show abstract

SPARC gene variants predict clinical outcome in locally advanced and metastatic pancreatic cancer patients

Cited by 8 publications

References 27 publications

The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma

Identification of hub genes in peripheral blood mononuclear cells for the diagnosis of hepatocellular carcinoma using a weighted gene co‑expression network analysis

Secreted protein acidic and rich in cysteine gene variants: Impact on susceptibility and survival of hepatocellular carcinoma patients

Contact Info

Product

Resources

About