FSIP1 is correlated with estrogen receptor status and poor prognosis

Li, Xuelu; Song, Xiaoqing; Ma, Jing; Zhao, Yu; Jiang, Qinyan; Zhao, Zuowei; Li, Man

doi:10.1002/mc.23134

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…1A ). Among the 7 genes, GATA3 , FSIP , and FOXA1 have been suggested to associate with chemoresistance in ER-positive breast cancers 16 , 22 . Notably, in both Cancer Genomic Atlas (TCGA) and CCLE databases, the meiotic gene SYCP2 is commonly upregulated in breast, cervical, and ovarian cancers and also detected in other cancer types, including lung, head-and-neck, and bladder cancers (Fig.…”

Section: Resultsmentioning

confidence: 99%

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

Wang,

Gao,

Zhang

et al. 2024

Nat Commun

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Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.

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Section: Resultsmentioning

confidence: 99%

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

Wang,

Gao,

Zhang

et al. 2024

Nat Commun

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“…In the field of tumor biology, FSIP1 is currently recognized as a cancer antigen which is highly expressed in breast, colon, lung, and bladder cancers and associated with poor prognosis. In breast cancer tissues, it has been found that FSIP1 expression is correlated with HER2 positive and Ki67 expression, and it is associated with poorer postoperative disease-specific survival probability [22]. Studies confirmed that FSIP1 directly binded to HER2 and inhibited the expression of multiple growth factors in HER2positive breast cancer cells, leading to a decrease in cell proliferation, cell migration, and invasion capabilities and an increase in apoptosis.…”

Section: Disease Markersmentioning

confidence: 93%

FSIP1 Is Associated with Poor Prognosis and Can Be Used to Construct a Prognostic Model in Gastric Cancer

et al. 2022

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Gastric cancer (GC) is one of the most common upper gastrointestinal malignant tumors, and the incidence of the GC shows an increasing trend in the past years. Finding more sensitive markers will help to reveal the mechanism of GC progression and clinic diagnoses. This study first analyzed the mRNA expression level of FSIP1 in TCGA GC samples and the significance in predicting the prognosis. KEGG and GO analyses were used to explore the molecular mechanism of FSIP1 in GC progression. This study further retrospectively analyzed 166 clinical samples of GC from Harbin Medical University Cancer Hospital and evaluated the expression level of FSIP1 by immunohistochemistry. Kaplan-Meier and Cox multivariate analysis was used to investigate the prognostic value of FSIP1 expression in GC patients. We also identified correlations between FSIP1 and clinicopathological characteristics. This study found that the mRNA level of FSIP1 was significantly upregulated in GC compared with nontumor specimens and correlated with poor prognosis. Immunohistochemistry confirmed the results of bioinformatics analysis of the TCGA GC database. FSIP1 was associated with pTNM pathological stage, tumor location, and neural invasion. In addition, multivariate Cox regression analysis showed that FSIP1, T classification, and N classification were independent posterior factors of patients and could be combined with pathological features to construct a nomogram prognostic model. Overall, our results suggest that FSIP1 is expected to be an independent prognostic indicator of GC.

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“…Five days later, medium-Matrigel-cells were centrifuged, and cell pellets were embedded in histogel (Thermo Scientific; Cat#HG-4000-012). The mixture was fixed in 4% paraformaldehyde overnight followed by dehydration, paraffin embedding, sectioning, and immunohistochemistry was performed as previously described [9] . Rabbit anti-HER2 (1: 500) antibody was purchased from Abcam (ab134182).…”

Section: Methodsmentioning

confidence: 99%

FSIP1 is correlated with estrogen receptor status and poor prognosis

Cited by 6 publications

References 17 publications

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair

FSIP1 Is Associated with Poor Prognosis and Can Be Used to Construct a Prognostic Model in Gastric Cancer

A novel treatment strategy of HER2-targeted therapy in combination with Everolimus for HR+/HER2- advanced breast cancer patients with HER2 mutations

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