ArticleHeliyon2021
APE1 and SSRP1 is overexpressed in muscle invasive bladder cancer and associated with poor survival.
Article in Heliyon, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the APE1 hub: integrating DNA repair and redox signaling for precision management of inflammation-associated diseases.Molecular biology reports · 2026Review
- APE1 condensation in nucleoli of non-cancer cells depends on rRNA transcription and forming G-quadruplex RNA structures.Nucleic acids research · 2025Article
- Development and validation of a novel signature to predict the survival and affect the immune microenvironment of esophageal squamous cell carcinoma: epigenetic-related genes.Frontiers in immunology · 2025Article
- The FAcilitates Chromatin Transcription complex regulates the ratio of glycolysis to oxidative phosphorylation in neural stem cells.Journal of molecular cell biology · 2024Article
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- SFPQ promotes the proliferation, migration and invasion of hepatocellular carcinoma cells and is associated with poor prognosis.American journal of cancer research · 2023Article
- Tandem Affinity Purification and Mass-Spectrometric Analysis of FACT and Associated Proteins.Methods in molecular biology (Clifton, N.J.) · 2023Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- Histone chaperone FACT complex inhibitor CBL0137 interferes with DNA damage repair and enhances sensitivity of medulloblastoma to chemotherapy and radiation.Cancer letters · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman apurinic/apyrimidinic (AP) endonuclease 1 (APE1) plays a critical role in DNA base excision repair (BER) pathway and has been reported to be overexpressed in multiple cancers. Previously, we have shown that histone chaperone FACT complex (Facilitates Chromatin Transcription, a heterodimer of SSRP1 and SPT16 proteins) facilitates the chromatin access and DNA repair function of APE1, and their expression levels are correlated with promoting drug resistance in cancer. FACT inhibitor has been introduced in phase I and II clinical trials for chemosensitization of advanced solid cancers. However, the expression profile and prognostic significance of APE1 and FACT complex in bladder cancer remains largely unknown.
methodsRetrospectively, 69 bladder cancer samples were retrieved and submitted for immunohistochemical staining of APE1 and SSRP1. Expression profile including cytoplasmic and nuclear staining of APE1 and expression level of SSRP1 was examined and semi-quantified to render a H-score. The prognostic significance of APE1 and SSRP1 was evaluated by Kaplan-Meier survival analysis in our cohort and R2 database.
resultsAPE1 expression is elevated in bladder cancer compared to normal adjacent tissues. Compared with low grade tumors, high grade tumors show a shift in the staining pattern including higher intensity and positive cytoplasmic staining. Carcinoma in situ has a similar staining pattern to high grade tumors. APE1 and SSRP1 staining intensity increases as tumor progresses with stage. There is a correlation between APE1 and SSRP1 staining in invasive bladder cancer (Spearman r = 0.5466, p < 0.0001). The increased expression of APE1 and SSRP1 is associated with poor survival in Kaplan-Meier analysis in our cohort and in R2-TCGA bladder cancer database.
conclusionsThe expression levels of APE1 and SSRP1 are significantly elevated in bladder cancer as compared to normal adjacent tissues. APE1 correlates with SSRP1 expression in high grade tumors. Overexpression of APE1 and SSRP1 is associated with poor survival in bladder cancer. This suggests the usage of FACT inhibitor curaxins in muscle invasive bladder cancer to target FACT complex and APE1 to improve chemosensitization after further validation.
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