High expression of SLC20A1 is less effective for endocrine therapy and predicts late recurrence in ER-positive breast cancer

Onaga, Chotaro; Tamori, Shoma; Matsuoka, Izumi; Ozaki, Ayaka; Motomura, Hitomi; Nagashima, Yuka; Sato, Tsugumichi; Sato, Keiko; Xiong, Yuyun; Sasaki, Kazunori; Ohno, Shigeo; Akimoto, Kazunori

doi:10.1371/journal.pone.0268799

Cited by 5 publications

(14 citation statements)

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“…an urgent need for the development of effective biomarkers for prognosis and treatment targets for diverse individual tumours of different subtypes. We have previously published a series of articles in recent years and screened a number of genes playing a key role in the diagnosis, prognosis, and therapy for each subtype of breast cancer (7)(8)(9)(10)(11)(12)(13)(14)(15). Hence, the present study continued the search for characteristic genes and the identification of explicit gene functions among different subtypes in breast cancer.…”

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confidence: 96%

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Xiong¹,

Motomura²,

Tamori³

et al. 2022

Anticancer Res

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Background/Aim: CD58 is an immune adhesion molecule on the cellular surface. It was previously found that a high expression of CD58 predicted a poor prognosis of patients with lower-grade gliomas. Therefore, the aim of this paper was to investigate the association between CD58 and breast cancer. Materials and Methods: CD58 gene expression data downloaded from cBioPortal was compared between the different subtypes of breast cancer. Clinical prognosis was examined using Kaplan-Meier analysis and multivariable Cox regression analysis. The association between CD58 expression and immune cell infiltration was estimated using the TIMER 2.0 web platform. Finally, the tumour sphere formation of aldehyde dehydrogenase 1 (ALDH1) high basallike breast cancer stem cells in which CD58 was knocked down using siRNA was measured. Results: CD58 mRNA was mainly enriched in claudin-low and basal-like subtypes. The high expression of CD58 predicted a good prognosis in patients with luminal A and luminal B breast cancer. This prediction may be due to the association of immune cell infiltration with CD58. Notably, patients with luminal A breast cancer with a high expression of CD58 in association with ALDH1A3 exhibited a good prognosis; however, this did not apply to patients with basal-like breast cancer. The in vitro experiments revealed that knockdown of CD58 inhibited the tumour sphere formation ability of ALDH1 high basal-like cancer cells. Conclusion: CD58 may function as a potential prognostic biomarker and therapeutic target in ALDHpositive basal-like cancer stem cells.According to the enumeration published in 2022, over 287,000 new cases of breast cancer have been estimated to be diagnosed in the United States each year, with breast cancer accounting for 31% of all cancers among females. In addition, over 43,000 women are estimated to succumb to the disease each year (1). Breast cancer is a heterogeneous disease which can be subtyped by predictive analysis of the microarrays 50 (PAM50) gene panel. Breast cancer PAM50 molecular subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, basallike, normal-like and claudin-low. Luminal A and B subtypes are mainly associated with oestrogen receptor (ER) + cancers (2, 3), while the majority of triple-negative breast cancers (TNBCs) are also classified as claudin-low and basal-like subtypes (4).Based on the subtyping, treatment of breast cancer mainly entails surgery, radiotherapy, and drug therapy, including chemotherapy, endocrine therapy and molecular targeted therapy. In general, patients with luminal A breast cancer have a favourable prognosis owing to the effectiveness of anti-hormone receptor therapy (5). By contrast, patients with the basal-like subtype have an unfavourable prognosis due to resistance to conventional therapy (6). Therefore, there is 5223

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confidence: 96%

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Xiong¹,

Motomura²,

Tamori³

et al. 2022

Anticancer Res

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“…The METABRIC dataset (46,47) was downloaded from cBioPortal (48,49) on January 12, 2021. The clinicopathological data of these patients have been summarized previously (50)(51)(52). The METABRIC dataset has disease-specific survival (DSS) data with mRNA expression levels (n=1,423) and data regarding radiotherapy (luminal A: without radiotherapy, n=192, with radiotherapy, n=269; luminal B: without radiotherapy, n=115, with radiotherapy, n=224).…”

Section: Methodsmentioning

confidence: 99%

“…Prognostic analyses. The Kaplan-Meier method, log-rank (Cochran-Mantel-Haenszel) test and multivariate Cox regression analyses of DSS were performed as previously described (35,(50)(51)(52)(57)(58)(59)(60)(61)(62)(63)(64). Briefly, to divide patients into groups of high and low p62 and ALDH1A3 gene expression, receiver operating characteristic curves were drawn using DSS data, and the Youden index was used as the ANTICANCER RESEARCH 44: 37-47 (2024) Cell culture.…”

Section: Methodsmentioning

confidence: 99%

Luminal B Breast Cancer Coexpressingp62andALDH1A3Is Less Susceptible to Radiotherapy

OZAKI,

MATSUDA,

MAEMURA

et al. 2023

Anticancer Res

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Background/Aim: We have reported that p62 (also known as sequestosome 1) is needed for survival/proliferation and tumor formation by aldehyde dehydrogenase 1 (ALDH1) -positive cancer stem cells (CSCs) and that p62 high ALDH1A3 high expression is associated with a poor prognosis in luminal B breast cancer. However, the association between p62 high ALDH1A3 high and the benefit from radiotherapy in patients with luminal B breast cancer remains unclear. Materials and Methods: Datasets from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) were downloaded, and data from p62 high ALDH1A3 high luminal B patients treated without or with radiotherapy were analyzed by Kaplan-Meier and multivariate Cox regression analyses. We also performed an in vitro tumor sphere formation assay after X-ray irradiation using p62-knockdown ALDH1 high luminal B BT-474 cells. Results: p62 high ALDH1A3 high patients had poorer clinical outcomes than other luminal B breast cancer patients treated with radiotherapy. The combination of p62 DsiRNA KD and X-ray irradiation suppressed in vitro tumor sphere formation by ALDH1 high BT-474 cells. These results suggest that p62 is involved in the reduced effect of X-ray irradiation on ALDH1-positive luminal B breast CSCs. Conclusion: p62 and ALDH1A3 may serve as prognostic biomarkers for luminal B breast cancer patients treated with radiotherapy. Additionally, the combination of p62 inhibition and radiotherapy could be useful for targeted strategies against ALDH1-positive luminal B breast CSCs.

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“…More advanced stages of tumor luminal A breast cancer were associated with increased SLC20A1 expression, according to a previous investigation. Moreover, this SLC20A1 high subset of individuals showed worse responses to endocrine treatment, particularly in breast cancer luminal A and B subtypes [ 18 ]. Nonetheless, the association between SLC20A1 and the prognosis of patients with HNSCC are rarely reported.…”

Section: Introductionmentioning

confidence: 99%

SLC20A1 is a prospective prognostic and therapy response predictive biomarker in head and neck squamous cell carcinoma

Qian,

Jin,

Bei

et al. 2024

Aging

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Background: SLC20A1, a prominent biomarker in several cancers, has been understudied in its predictive role in head and neck squamous cell carcinoma (HNSCC). Methods: The Cancer Genome Atlas (TCGA) database was used to analyze HNSCC prognosis, SLC20A1 overexpression, and clinical characteristics. Quantitative real-time PCR and Western blot analysis confirmed SLC20A1 expression in HNSCC tissues. Cellular behaviors such as invasion, migration and proliferation were assessed using Transwell, wound healing and colony formation assays. Immune system data were obtained from the Tumor Immune Estimation Resource (TIMER) and CIBERSORT databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore biological parameters and pathways associated with SLC20A1 overexpression in HNSCC. Results: In 499 HNSCC samples, SLC20A1 mRNA and protein expression were significantly higher than in 44 normal counterparts, confirmed by 24 paired samples. Patients were categorized based on SLC20A1 levels, survival status and overall survival. High SLC20A1 expression correlated with advanced T stage, increased risk scores and decreased survival. Stage, age and SLC20A1 expression emerged as independent predictive factors for HNSCC in univariate and multivariate analyses. SLC20A1 overexpression, which is associated with poor prognosis, may influence cell proliferation, migration, invasion, chemotherapy response, and the immune milieu. Conclusions: SLC20A1 overexpression in HNSCC, characterized by increased cellular invasion, migration and proliferation, is a potential prognostic biomarker and therapeutic response indicator.

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High expression of SLC20A1 is less effective for endocrine therapy and predicts late recurrence in ER-positive breast cancer

Cited by 5 publications

References 41 publications

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Luminal B Breast Cancer Coexpressingp62andALDH1A3Is Less Susceptible to Radiotherapy

SLC20A1 is a prospective prognostic and therapy response predictive biomarker in head and neck squamous cell carcinoma

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