Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer

Zhou, Xiaoling; Xie, Sheng; Yuan, Chunluan; Jiang, Li; Huang, Xiaoyan; Li, Liumei; Chen, Yan; Luo, Lichuan; Zhang, Jianxuan; Wang, Daogang; Liu, Lijian; Shi, Wei; Han, Liang; Tang, Nong; Ji, Yunxi

doi:10.1159/000453195

Cited by 18 publications

(19 citation statements)

References 17 publications

(26 reference statements)

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“…Identifying novel genes that are clinically significant for the progression and chemoresistance of breast cancer is critical for evaluating prognosis and treatment of this disease. Although many genes might become prognostic indicators of breast cancer [2, 3], some tumour suppressors have been used for molecular targeted therapy [4]. …”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. Conclusion: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.

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Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Zhang

et al. 2018

Cell Physiol Biochem

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“…The expression of Sprouty2 is reported to be reduced in human CRC and is inversely correlated with the expression of miR‐21 . The expression level of Sprouty4 is also reduced in human CRC due to DNA methylation and serves as an independent predictor of overall survival . The expression of Sprouty2, which promotes the cytotoxic effect of 5‐fluorouracil and metformin, is downregulated by miR‐21 in a human colon cancer cell line .…”

Section: Roles Of Sprouty/spred During Tumorigenesis and Metastasismentioning

confidence: 99%

“…37 The expression level of Sprouty4 is also reduced in human CRC due to DNA methylation and serves as an independent predictor of overall survival. 36 The expression of Sprouty2, which promotes the cytotoxic effect of 5-fluorouracil and metformin, is downregulated by miR-21 in a human colon cancer cell line. 65 Sprouty2 also increases the sensitivity to gefitinib, an EGFR inhibitor, by increasing the expression of phosphorylated and total EGFR in human CRC cell lines.…”

Section: Sprouty/spred and Crcmentioning

confidence: 99%

The Sprouty/Spred family as tumor suppressors: Coming of age

Kawazoe

Taniguchi

2019

Cancer Science

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The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.

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“…gene expression) and epigenetic (e.g. DNA methylation) aberrations have been associated with patient survival [5,[10][11][12]. For instance, overexpression of immune checkpoint regulator PD-L2 was recently reported to be associated with poor survival [13].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Network-Based Analysis of Colorectal Cancer Identifies Novel Prognostic Factors and an Integrative Prognostic Index

Hou

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is one of leading cancers in both incidence and mortality rate. The 5-year survival rate varies considerably depending on the pathological stage of the tumor. Although prominent progress has been made through screening for survival-associated factors from a certain type of genetic or epigenetic modifications, few attempts have been made to apply a network-based approach in prognostic factor identification, which could prove valuable for a complex, multi-faceted disease such as CRC. Methods: In this study, a TCGA dataset of 379 CRC patients was subjected to a network-based analysis strategy consisting of multivariate regression, co-expression network and gene regulatory network analyses, and survival analyses. Both genetic and epigenetic aberrations, including those in gene expression and DNA methylation at specific sites, were screened for significant association with patient survival. A prognostic index (PI) integrating all potential prognostic factors was subsequently validated for its prognostic value. Results: A collection of six miRNAs, eleven mRNAs, and nine DNA methylation sites were identified as potential prognostic factors. The low- and high-risk patient groups assigned based on PI level showed significant difference in overall survival (hazard ratio = 1.32, 95% confidence interval 1.29-1.36, p < 0.0001). Patients in the low- and high-risk groups can be further divided into a total of four subgroups, based on pathological staging. In the two high-risk subgroups (PI > 0), there was significant different (Cox p < 0.0001) in OS between the earlier (stages I/II) and later stages (stages III/IV). However, in the two low-risk subgroups (PI < 0), earlier (stages I/II) and later stages (stages III/IV) showed no significant difference in OS (Cox p = 0.185). On the other hand, there were significant differences in OS between the low- and high-risk subgroups when both subgroups were of earlier stages (Cox p < 0.001) or of later stages (Cox p < 0.0001). Conclusion: The novel network-based, integrative analysis adopted in this study was efficient in screening for prognostic predictors. Along with PI, the set of 6 miRNAs, 11 mRNAs, and 9 DNA methylation sites could serve as the basis for improved prognosis estimation for CRC patients in future clinical practice.

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Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer

Cited by 18 publications

References 17 publications

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

The Sprouty/Spred family as tumor suppressors: Coming of age

Genome-Wide Network-Based Analysis of Colorectal Cancer Identifies Novel Prognostic Factors and an Integrative Prognostic Index

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