Overexpression of SLC12A5 is associated with tumor progression and poor survival in ovarian carcinoma

Yang, Gui Ping; He, Wei; Jin, Tan; Yang, Zun Xian; Fan, Rong; Fang, Ning; Wang, Feng Wei; Chen, Li; Yang, Li; Shen, Hong; You, Ze Shan; Xie, Dan; Yang, Guowei

doi:10.1136/ijgc-2019-000229

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…Our findings of gene expression and breast cancer prognosis were consistent with the previous evidence for HSP90AA1 [ 37 ], ADCY4 [ 38 ], and GNG7 [ 39 ]. High SLC12A5 expression was suggested to predict poor survival in patients with bladder urothelial [ 40 ], colorectal [ 41 ] and ovarian [ 42 ] cancers, whereas the association direction in breast cancer was found the opposite in our study. However, our results is consistent between the WCH and TCGA samples as well as in line with public data source (e.g.…”

Section: Discussioncontrasting

confidence: 59%

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts

Wang

Luo

et al. 2022

BMC Cancer

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Background Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue. Methods We conducted an extreme case–control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively. Results In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07–2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2–35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA. Conclusion Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.

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Section: Discussioncontrasting

confidence: 59%

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts

Wang

Luo

et al. 2022

BMC Cancer

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“…Besides the essential physiological functions, SLC transporters are associated with various pathological processes, including tumorigenesis and chemotherapy resistance ( 12 , 13 ). The solute carrier family 12 member 5 (SLC12A5), which is an integral membrane KCl cotransporter, has been reported to be amplified in colorectal and ovarian cancers, serving as a putative driver gene in these cancers ( 14 , 15 ). In HCC, SLC27A5 was found to be a tumor suppressor and suppressed TXNRD1 expression via the KEAP1/NRF2 pathway ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma

Cao¹,

Wang²,

Chen³

et al. 2021

Transl Cancer Res TCR

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Background: Solute carrier (SLC) transporters play important roles in various physiological and pathological processes, such as cellular uptake of nutrients, cellular metabolism, tumor initiation and chemotherapy resistance. However, little is known about the comprehensive expression profile of SLC genes in human cancers, especially in human hepatocellular carcinoma (HCC).Methods: Comprehensive analysis was performed using the TCGA dataset to evaluate the expression profile and clinical significance of SLC family genes in HCC. Real-time PCR and immunohistochemistry (IHC) assays were conducted to validate the expression of solute carrier family 26 member 6 (SLC26A6) in clinical HCC tissues. Cell Counting Kit-8 (CCK8), colony formation and subcutaneous xenograft tumorigenesis assays were carried out to explore the functional role of SLC26A6 in HCC. Bioinformatic analyses were used to predict the potential molecular mechanism of SLC26A6 in HCC.Results: We identified 118 differentially expressed SLC genes (DESLCs) and found that there was a preferential enrichment for activated DESLCs in HCC. Clinical-relevant DESLCs identified a poor prognostic HCC subtype exhibiting unique clinicopathological and genomic profiles. SLC26A6 was overexpressed in HCC tissues both in mRNA and protein levels. Knockdown of SLC26A6 suppressed HCC tumorigenesis both in vitro and in vivo, indicating it as a promising therapeutic target. Finally, multifaceted bioinformatic analyses indicated that SLC26A6 might associate with multiple cancer-related pathways.Conclusions: This study highlights the potential roles of SLC genes in HCC tumorigenesis, and suggested SLC26A6 as a promising therapeutic target in HCC patients.

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“…Paraffin-embedded tissues were cut into 4-μm-thick sections. The immunohistochemistry procedure to determine CXCL14 and β-catenin expression was performed as described previously [ 16 , 17 ]. To evaluate CXCL14 or β-catenin staining, its extent was scored by assigning a staining percentage to positive tumor cells (0, none; 1,< 20% of positive staining cells; 2, 20–50% of positive staining cells; 3,> 50% of positive staining cells).…”

Section: Methodsmentioning

confidence: 99%

CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/β-catenin signaling pathway

et al. 2021

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Background There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial–mesenchymal transition (EMT). Methods qRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The migration ability of OC cell was determined using wound healing. The protein expressions of CXCL14 and β-catenin in OC tissues were determined by immumohistochemical staining. Results We demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth, migration and invasion of OC cell in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/β-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness. Conclusion These data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/β-catenin signaling pathway.

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Overexpression of SLC12A5 is associated with tumor progression and poor survival in ovarian carcinoma

Cited by 10 publications

References 13 publications

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts

Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma

CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/β-catenin signaling pathway

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