Expression of Secreted Protein Acidic and Rich in Cysteine in the Stroma of a Colorectal Carcinoma is Associated With Patient Prognosis

Kim, Jeong Yeon; Jeong, Dongjun; Ahn, Tae Sung; Kim, Hyung Ju; Park, Doo San; Park, So Yong; Bae, Sang Byung; Lee, Sook-Young; Lee, Sungsoo; Lee, Moon Soo; Cho, Hyun Deuk; Baek, Moo Jun

doi:10.3393/ac.2013.29.3.93

Cited by 15 publications

(11 citation statements)

References 26 publications

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“…Altered levels of TGF-β, a main mediator of communication between the tumor and its micro-environment, can cause cancer progression by stimulation of angiogenesis, tumor immune escape, and recruitment of myofibroblasts [19]. Moreover, secreted protein acidic and rich in cysteine (SPARC), a matricellular protein that promotes the interaction between tumor cells and substrates, was reported to be strongly expressed in the stroma cells of pancreatic adenocarcinoma, non-small cell lung cancer, and colorectal carcinoma [20][21][22]. Changes in the stroma could thus promote the invasion and metastasis of tumors.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of the tumor-stroma ratio in gallbladder cancer

Li¹,

Yuan²,

Han³

et al. 2017

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In recent years, the tumor-stroma ratio (TSR) has attracted increasing attention as an independent prognostic factor for several solid tumors. However, the importance of the stromal compartment has not been investigated yet in gallbladder cancer (GBC). The objective of this study is to investigate the prognostic value of TSR in GBC and the relationship between TSR and other known prognostic parameters. A total of 51 patients who underwent operations for gallbladder carcinoma were selected for this study. TSR was determined on haematoxylin and eosin (H et E)-stained sections by two independent investigators. Stromal ratio groups were classified as stroma-poor (ratio of stroma 50%). The Mann-Whitney test, the Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazards model were used to analyze the data. The median survival time for patients in the stroma-rich group was 6.00 months (95% CI, 4.47-7.54). In contrast, for the stroma-poor group, the median survival time was 17.00 months (95% CI, 3.64-30.36). The 3-year overall survival rate was 19.7% in the stroma-poor group and 7.2% in the stroma-rich group. Patients with stroma-rich tumors had a worse prognosis than those with stroma-poor tumors (log-rank P = 0.004). According to the univariate analysis, the TSR, differentiation grade, pTNM stage, and operative methods were shown to be related to overall survival (OS) with statistical significance. The hazard ratio (HR) of TSR was 2.428 (95% CI, 1.29-4.58; P = 0.006). However, the TSR did not prove to be an independent prognostic factor in the multivariate analysis. Our study demonstrated that the tumor-stroma ratio (TSR) is an important prognostic parameter for gallbladder cancer (GBC). Stroma-rich tumors were associated with poor overall survival.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of the tumor-stroma ratio in gallbladder cancer

Li¹,

Yuan²,

Han³

et al. 2017

neo

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“…Briefly, the number of patients in each study ranged from 36 to 1,093, and a total of 5,939 patients from 11 countries were included in the present meta-analysis. The studies focused on solid tumors, including gastric cancer,11,16-18 esophageal squamous cell carcinoma,19,20 pancreatic cancer,8,21-25 lung cancer,10,26,27 breast cancer,4,9,28 colorectal cancer,29-32 diffuse large B-cell lymphoma,12,33 biliary tract cancer,7 and nasopharyngeal carcinoma 34. The positive rates of SPARC varied among the 9 solid tumors, and in the same tumor type, the positive rates of SPARC expressed in cancer and stromal cells were also different ( Figure 1B ).…”

Section: Resultsmentioning

confidence: 99%

Prognostic role of secreted protein acidic and rich in cysteine in patients with solid tumors

Chen

et al. 2019

SMJ

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Objectives: To analyze the heterogeneous functions of secreted protein acidic and rich in cysteine (SPARC) from different origins and in different tumor microenvironments with the purpose of determining its clinical significance. Methods: The PubMed, CINAHL, Cochrane, Web of Science and Embase databases were utilized. Studies that focused on the effects of SPARC expression on solid tumor progression and clinical implications were used. The different outcomes including overall survival and disease-free survival were analyzed to evaluate their relations with tumor- and stroma-derived SPARC expression. Results: A total of 26 studies including 5,939 patients were enrolled in the present meta-analysis. Tumor-derived SPARC overexpression was significantly related with poor overall survival (hazard ratio: 1.478; 95% CI: 1.143-1.910; p=0.003), and a similar tendency was also observed in disease-free survival (hazard ratio: 1.476; 95% CI: 0.993-2.195; p=0.054). However, the hazard ratios for overall survival and disease-free survival did not present a statistical trend in stromal SPARC overexpression. Tumor type subgroup analysis revealed marked heterogeneity among outcomes. In pancreatic cancer, SPARC overexpression in the stroma was significantly associated with poorer overall survival and disease-free survival. In colorectal cancer, SPARC overexpression in the stroma was associated with better disease-free survival. Conclusion: For the majority of solid tumors, SPARC in cancer cells may be an unfavorable indicator for long-term survival for patients. As for stromal expression, SPARC indicates a poorer prognosis in pancreatic cancer, but a better disease-free survival in colorectal cancer. Secreted protein acidic and rich in cysteine might be a potential biomarker for solid tumor prognosis.

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“…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

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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.

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Expression of Secreted Protein Acidic and Rich in Cysteine in the Stroma of a Colorectal Carcinoma is Associated With Patient Prognosis

Cited by 15 publications

References 26 publications

Prognostic significance of the tumor-stroma ratio in gallbladder cancer

Prognostic significance of the tumor-stroma ratio in gallbladder cancer

Prognostic role of secreted protein acidic and rich in cysteine in patients with solid tumors

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

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