The association between SPINK1 and clinical outcomes in patients with prostate cancer: a systematic review and meta-analysis

Zhang, Xingming; Yin, Xiaoxue; Shen, Pengfei; Sun, Guangxi; Yang, Yaojing; Liu, Jiandong; Chen, Ni; Zeng, Hao

doi:10.2147/ott.s127317

Cited by 19 publications

(13 citation statements)

References 25 publications

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“…Ida et al [22] demonstrated that SPINK1 stimulates the proliferation of colon cancer cells and is involved in colorectal cancer progression. Moreover, overexpression of SPINK1 is associated with adverse prognosis in other cancers, including prostate cancer [23], hepatocellular cancer [24] and breast cancer [25]. Thus, SPINK1 can be used as a prognostic tumor marker.…”

Section: Discussionmentioning

confidence: 99%

Downregulated SPINK4 is associated with poor survival in colorectal cancer

Wang

Ghareeb

et al. 2019

BMC Cancer

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BackgroundSPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown.MethodsWe retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center.ResultsSPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort.ConclusionsWe concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

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Section: Discussionmentioning

confidence: 99%

Downregulated SPINK4 is associated with poor survival in colorectal cancer

Wang

Ghareeb

et al. 2019

BMC Cancer

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“…Molecular studies have led to the characterization in mCRPC patients of a subgroup comprising about 10% of cases with an overexpression of the SPINK1 gene, in association with negativity for ETS fusions [312]. SPINK1 overexpression is associated with a negative prognosis in patients with mCRPC, but not in those with localized disease [347]. The mechanisms responsible for SPINK1 overexpression are unclear, but it evident that it is not related to chromosomal rearrangement, deletion or amplification.…”

Section: Gene Expression Profiling Studiesmentioning

confidence: 99%

Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications

2019

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Prostate cancer is the most frequent nonskin cancer and second most common cause of cancer-related deaths in man. Prostate cancer is a clinically heterogeneous disease with many patients exhibiting an aggressive disease with progression, metastasis, and other patients showing an indolent disease with low tendency to progression. Three stages of development of human prostate tumors have been identified: intraepithelial neoplasia, adenocarcinoma androgen-dependent, and adenocarcinoma androgen-independent or castration-resistant. Advances in molecular technologies have provided a very rapid progress in our understanding of the genomic events responsible for the initial development and progression of prostate cancer. These studies have shown that prostate cancer genome displays a relatively low mutation rate compared with other cancers and few chromosomal loss or gains. The ensemble of these molecular studies has led to suggest the existence of two main molecular groups of prostate cancers: one characterized by the presence of ERG rearrangements (~50% of prostate cancers harbor recurrent gene fusions involving ETS transcription factors, fusing the 5′ untranslated region of the androgen-regulated gene TMPRSS2 to nearly the coding sequence of the ETS family transcription factor ERG) and features of chemoplexy (complex gene rearrangements developing from a coordinated and simultaneous molecular event), and a second one characterized by the absence of ERG rearrangements and by the frequent mutations in the E3 ubiquitin ligase adapter SPOP and/or deletion of CDH1, a chromatin remodeling factor, and interchromosomal rearrangements and SPOP mutations are early events during prostate cancer development. During disease progression, genomic and epigenomic abnormalities accrued and converged on prostate cancer pathways, leading to a highly heterogeneous transcriptomic landscape, characterized by a hyperactive androgen receptor signaling axis.

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“…In prostate cancer, EGFR signaling pathway induces SPINK1 trypsin inhibitor to promote EMT [ 63 ] and overexpression of SPINK1 represents its aggressive form [ 64 ]. Although studies have shown positive association of SPINK1 expression with biochemical recurrence and castration-resistant prostate cancer [ 65 ], there was no significant difference in SPINK1 expression between incidental and metastatic cases [ 66 ]. The positive correlation between SPINK1 and CD82 expression in PrEC-31 normal prostate cells remains unexplained without further studies.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of human prostate cell lines with and without tumor metastasis suppressor CD82

et al. 2020

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Background Tetraspanin CD82 is a tumor metastasis suppressor that is known to down regulate in various metastatic cancers. However, the exact mechanism by which CD82 prevents cancer metastasis is unclear. This study aims to identify genes that are regulated by CD82 in human prostate cell lines. Methods We used whole human genome microarray to obtain gene expression profiles in a normal prostate epithelial cell line that expressed CD82 (PrEC-31) and a metastatic prostate cell line that does not express CD82 (PC3). Then, siRNA silencing was used to knock down CD82 expression in PrEC-31 while CD82 was re-expressed in PC3 to acquire differentially-expressed genes in the respective cell line. Results Differentially-expressed genes with a P < 0.05 were identified in 3 data sets: PrEC-31 (+CD82) vs PrEC-31(−CD82), PC3–57 (+CD82) vs. PC3-5 V (−CD82), and PC3–29 (+CD82) vs. PC3-5 V (−CD82). Top 25 gene lists did not show overlap within the data sets, except (CALB1) the calcium binding protein calbindin 1 which was significantly up-regulated (2.8 log fold change) in PrEC-31 and PC3–29 cells that expressed CD82. Other most significantly up-regulated genes included serine peptidase inhibitor kazal type 1 (SPINK1) and polypeptide N-acetyl galactosaminyl transferase 14 (GALNT14) and most down-regulated genes included C-X-C motif chemokine ligand 14 (CXCL14), urotensin 2 (UTS2D), and fibroblast growth factor 13 (FGF13). Pathways related with cell proliferation and angiogenesis, migration and invasion, cell death, cell cycle, signal transduction, and metabolism were highly enriched in cells that lack CD82 expression. Expression of two mutually inclusive genes in top 100 gene lists of all data sets, runt-related transcription factor (RUNX3) and trefoil factor 3 (TFF3), could be validated with qRT-PCR. Conclusion Identification of genes and pathways regulated by CD82 in this study may provide additional insights into the role that CD82 plays in prostate tumor progression and metastasis, as well as identify potential targets for therapeutic intervention.

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The association between SPINK1 and clinical outcomes in patients with prostate cancer: a systematic review and meta-analysis

Cited by 19 publications

References 25 publications

Downregulated SPINK4 is associated with poor survival in colorectal cancer

Downregulated SPINK4 is associated with poor survival in colorectal cancer

Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications

Gene expression analysis of human prostate cell lines with and without tumor metastasis suppressor CD82

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