SPARCL1, a Novel Prognostic Predictive Factor for GI Malignancies: a Meta-Analysis

Hu, Hanguang; Cui, Wen; Zheng, Shu; Ge, Weiting

doi:10.1159/000485584

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…Previous analyses of hSPARCL1 expression in human tissues showed a preferential downregulation of expression in neoplastic tissues [5,[8][9][10][11][12][13][14][15]. This is also reflected by recent studies examining the effects of hSPARCL1 on tumorigenesis and metastasis formation [25][26][27][28][29][30]. However, there is still little information on the general expression patterns of SPARCL1 in human and murine tissues.…”

Section: Discussionmentioning

confidence: 99%

Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues

et al. 2020

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SPARCL1 is a matricellular protein with anti-adhesive, anti-proliferative and anti-tumorigenic functions and is frequently downregulated in tumors such as colorectal carcinoma or non-small cell lung cancer. Studies have identified SPARCL1 as an angiocrine tumor suppressor secreted by tumor vessel endothelial cells, thereby exerting inhibitory activity on angiogenesis and tumor growth, in colorectal carcinoma. It is unknown whether SPARCL1 may exert these homeostatic functions in all organs and in other species. Therefore, SPARCL1 expression was comparatively analysed between humans and mice in a systematic manner. Murine Sparcl1 (mSparcl1) is most strongly expressed in the lung; expressed at an intermediate level in most organs, including the large intestine; and absent in the liver. In human tissues, SPARCL1 (hSPARCL1) was detected in all organs, with the strongest expression in the stomach, large intestine and lung, mostly consistent with the murine expression pattern. A striking difference between human and murine tissues was the absence of mSparcl1 expression in murine livers, while human livers showed moderate expression. Furthermore, mSparcl1 was predominantly associated with mural cells, whereas hSPARCL1 was detected in both mural and endothelial cells. Human SPARCL1 expression was downregulated in different carcinomas, including lung and colon cancers. In conclusion, this study revealed species-, organ-and cell-type-dependent expression of SPARCL1, suggesting that its function may not be similar between humans and mice.

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Section: Discussionmentioning

confidence: 99%

Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues

et al. 2020

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“…A meta-analysis of eight studies including a total of 2356 patients revealed that its expression is associated with less lymph node and distant metastasis. The negative association between the SPARCL1 expression and poor tumour differentiation indicates the major role of aggressive tumour behavior [20]. In addition, the prognostic impact of SPARCL1 expression in ovarian and prostate cancers has also been reported [7,8].…”

Section: Discussionmentioning

confidence: 99%

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma

Luo

Chiang

Huang

et al. 2019

IJMS

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Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.

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“…To date, limited studies have reported that lower SPARCL1 expression suggests poor survival in human malignancies [ 27 – 32 ]. A meta-analysis revealed that SPARCL1 could predict poor clinical outcomes for gastrointestinal malignancies [ 33 ]. In our study, we pooled four clinical studies to explore the prognostic value of SPARCL1 in CRC.…”

Section: Discussionmentioning

confidence: 99%

SPARCL1 Is a Novel Prognostic Biomarker and Correlates with Tumor Microenvironment in Colorectal Cancer

Zhang

Liu

et al. 2022

BioMed Research International

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Background. Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) plays an important role in tumor pathogenesis. We aim to evaluate the clinical significance and potential biological roles of SPARCL1 in colorectal cancer (CRC). Methods. Datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were downloaded to evaluate the expression levels of SPARCL1 in CRC. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of SPARCL1. Then, comprehensive database search was conducted for published clinical studies to explore clinical significance of SPARCL1. In addition, coexpression genes of SPARCL1 were identified through the cBioPortal database and enrichment analysis of SPARCL1 and its coexpression genes were performed by the “clusterProfiler” R package. Finally, the correlations between SPARCL1 and tumor microenvironment scores, tumor-infiltrating immune cells in CRC were determined by “ESTIMATE” and “GSVA” R packages. Results. SPARCL1 was significantly downregulated in CRC tissues, and SPARCL1 showed high accuracy for diagnosis of primary CRC in both GEO and TCGA datasets. Pooled results from published clinical studies showed SPARCL1 expression was associated with differentiation ( OR = 1.89 , 95% CI: 1.38-2.59), tumor stage ( OR = 0.47 , 95% CI: 0.29-0.77), distant metastasis ( OR = 0.53 , 95% CI: 0.33-0.84), and overall survival ( HR = 0.56 , 95% CI: 0.43-0.74). SPARCL1 and its top 300 coexpression genes were involved in several KEGG pathways, such as focal adhesion, cell adhesion molecules, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, and ECM-receptor interaction. Besides, the SPARCL1 expression was significantly correlated with stromal score, immune score, ESTIMATE score, and diverse immune cells. Conclusion. SPARCL1 significantly correlated with clinicopathological features and tumor microenvironment in CRC.

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SPARCL1, a Novel Prognostic Predictive Factor for GI Malignancies: a Meta-Analysis

Cited by 8 publications

References 35 publications

Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues

Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues

Methylation of SPARCL1 Is Associated with Oncologic Outcome of Advanced Upper Urinary Tract Urothelial Carcinoma

SPARCL1 Is a Novel Prognostic Biomarker and Correlates with Tumor Microenvironment in Colorectal Cancer

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