APE1/Ref-1 as a Serological Biomarker for the Detection of Bladder Cancer

Shin, Ju Hyun; Choi, Sunga; Lee, Yu Ran; Park, Myoung Soo; Na, Yong Gil; Irani, Kaikobad; Lee, Sang Do; Park, Jin Bong; Kim, Jin Man; Lim, Jae Sung; Jeon, Byeong Hwa

doi:10.4143/crt.2014.074

Cited by 59 publications

(69 citation statements)

References 23 publications

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“…In the current study, we observed that in the tumor tissue, APE1 protein, an essential DNA repair enzyme in the BER pathway, could be a promising predictive biomarker for the responses of NSCLC patients receiving platinum-containing chemotherapy. Moreover, this previously reported nuclear protein was detected in the serum of NSCLC patients, and its level in the serum was directly correlated with the level measured in cancer tissue [12, 16, 17]. In addition, we describe herein, for the first time to our knowledge, that alteration of sAPE1 after chemotherapy is significantly associated with response and PFS of platinum-containing chemotherapy.…”

Section: Discussionsupporting

confidence: 63%

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Zhang

Dai

et al. 2016

Oncotarget

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PurposeTo define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy.ResultsOur investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010).Experimental DesignWe measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control.ConclusionsOur studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naïve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.

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Section: Discussionsupporting

confidence: 63%

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Zhang

Dai

et al. 2016

Oncotarget

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“…The correlation between clinical factors and serum APE1 was determined by the area of subject's characteristics under the curve. The results showed significant over-expression of serum APE1 in patients with bladder cancer, the sensitivity and specificity were 93% and 59%, respectively, and serum APE1 expression was related to tumor staging, grading, myometrial invasion and recurrence, suggesting that serum APE1 may serve as a potential serum marker of bladder cancer (16). Some studies also found that serum APE1 level was significantly elevated in 229 of 412 patients with non-small cell lung cancer and was correlated with tissue level (r 2 = 0.639, p < 0.001).…”

Section: Discussionmentioning

confidence: 93%

Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells

Sun

Zhu

Aminbuhe

et al. 2018

BST

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2. Materials and Methods 2.1. Tissue samples and main reagents Tissue samples and experimental cells: HCC tissue microarrays were purchased from Shanghai Outdo Biotech (model HLivH160CS01); there were 80 cases of HCC, 1 each at cancer/paracancerous site. TNM staging was available, clinical phase 1, 2, 3 and 4, Summary This research aimed to investigate the differential expression of apurinic-apyrimidinic endonuclease 1 (APE1) in hepatocellular carcinoma (HCC) tissues and cells and the effects on proliferation and apoptosis of cancer cells. Immunohistochemical techniques were used to detect the expression of APE1 in 80 cases of HCC and the corresponding paracancerous tissue microarrays; meanwhile, Western blots were used to detect the expression of APE1 in both human HCC BEL-7402, BEL-7405, HCC-9204, Hep3B, HepG2, SMMC-7721 and Huh-7 cells, and normal hepatocyte L-02 cells. The relationship between APE1 expression and clinical pathological characteristics of HCC was statistically analyzed. APE1 shRNA vector was constructed in Hep 3B cells to establish a stably transfected cell line, using Western blots to determine the interference efficiency. Cell proliferation activity was detected with MTT assays, while apoptosis was detected with the Annexin V-FITC/PI double-labeling technique. The expression of APE1 in HCC tissues and cells was significantly up-regulated, and its expression was significantly different from TNM staging and histopathological grading. Down-regulation of APE1 expression significantly reduced the proliferative activity and increased the apoptosis rate of Hep 3B cells. In conclusion, APE1 demonstrates cancer progression potential at the clinical, tissue and cell level. It provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.

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“… 273 A smaller study from 2015 showed higher sensitivity (90%) but lower specificity (59%) for utilizing Ref-1/APE1 in serum to detect bladder cancer. 274 Quantitative, noninvasive measurement of Ref-1/APE1 expression in urine or serum may 1 day become a diagnostic biomarker for bladder cancer as well as other cancers with additional studies in this area.…”

Section: Precision Oncology- Biomarkersmentioning

confidence: 99%

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

et al. 2017

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Reduction-oxidation factor 1-apurinic/apyrimidinic endonuclease (Ref-1/APE1) is a critical node in tumor cells, both as a redox regulator of transcription factor activation and as part of the DNA damage response. As a redox signaling protein, Ref-1/APE1 enhances the transcriptional activity of STAT3, HIF-1α, nuclear factor kappa B, and other transcription factors to promote growth, migration, and survival in tumor cells as well as inflammation and angiogenesis in the tumor microenvironment. Ref-1/APE1 is activated in a variety of cancers, including prostate, colon, pancreatic, ovarian, lung and leukemias, leading to increased aggressiveness. Transcription factors downstream of Ref-1/APE1 are key contributors to many cancers, and Ref-1/APE1 redox signaling inhibition slows growth and progression in a number of tumor types. Ref-1/APE1 inhibition is also highly effective when paired with other drugs, including standard-of-care therapies and therapies targeting pathways affected by Ref-1/APE1 redox signaling. Additionally, Ref-1/APE1 plays a role in a variety of other indications, such as retinopathy, inflammation, and neuropathy. In this review, we discuss the functional consequences of activation of the Ref-1/APE1 node in cancer and other diseases, as well as potential therapies targeting Ref-1/APE1 and related pathways in relevant diseases. APX3330, a novel oral anticancer agent and the first drug to target Ref-1/APE1 for cancer is entering clinical trials and will be explored in various cancers and other diseases bringing bench discoveries to the clinic.

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APE1/Ref-1 as a Serological Biomarker for the Detection of Bladder Cancer

Cited by 59 publications

References 23 publications

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells

Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic

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