XPA expression is a predictive marker of the effectiveness of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Wada, Takuya; Fukuda, Takahiro; Shimomura, Masahiro; Inoue, Yuta; Kawanishi, Masaru; Tasaka, Reiko; Yasui, Toshihiro; Ikeda, Kazuo; Sumi, Toshiyuki

doi:10.3892/ol.2018.7810

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Zhang et al found that the XPA rs1800975 polymorphism could decrease the incidence and risk of breast cancer in a large sample of patients ( 27) and Prochnow et al reported that high XPA expression significantly increased overall survival rates in patients with oropharyngeal squamous cell carcinomas (28). Further, Wada et al revealed that XPA expression was decreased in uterine cervical cancer and could be a predictive marker of neoadjuvant chemotherapy (29). Despite these clinical findings, the detailed molecular mechanism by which XPA mediates cancer related responses and processes require elucidation.…”

Section: Discussionmentioning

confidence: 99%

XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

Deng

Chen

Huang

et al. 2021

J Gastrointest Oncol

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Background: To explore the potential biological function of XPA (Xeroderma pigmentosum group A) in hepatic neoplasms and the underlying molecular mechanisms.Methods: Liver cells were used as experimental models to establish HCC (hepatocellular carcinoma) in vitro. Protein extractions were subjected to Western blotting to detect the proteins expression. The lentivirus transfection efficiency was confirmed by Western blot and RT-qPCR, Tunnel staining was used to detect apoptosis, and Transwell assays were used to observe cell migration and invasion. Cell proliferation was detected with colony formation and CCK-8 (cell counting kit-8) assays. Results: XPA expression was obviously lower in HCC tissue and liver cancer cell lines. XPA overexpression induced autophagy and apoptosis by increasing LC3B II/I, Beclin1, cleaved-caspase-3, and Bax expression and decreasing p62 and Bcl2 protein levels. XPA also suppressed HCC EMT (Epithelial-Mesenchymal Transition) by increasing E-cadherin and decreasing N-cadherin and vimentin protein expression. Cell proliferation, migration and invasion in vivo were significantly inhibited by the overexpression of XPA, and p-PI3K, p-Akt, and p-mTOR expression were decreased in LV-XPA cells. In general, XPA inhibited HCC by inducing autophagy and apoptosis and by modulating the expression of PI3K/Akt/mTOR proteins.Conclusions: XPA overexpression was found to suppress HCC by inducing autophagy and apoptosis and repressing EMT and proliferation. Each of these effects may be involved in modulating the PI3K/Akt/ mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

Deng

Chen

Huang

et al. 2021

J Gastrointest Oncol

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“…A possible association between XPA expression in tumour tissue and the efficacy of neoadjuvant chemotherapy (NAC) was investigated for locally advanced uterine cervical cancer (UCC). It was shown that the patients who responded to NAC displayed significantly lower XPA expression than those with ineffective NAC response, indicating that low XPA expression may be a predictive biomarker of NAC efficacy for patients with locally advanced UCC, which may be helpful for improving their prognosis [202].…”

Section: Xpa Expression As a Cancer Risk Factor And Its Prognostic And Predictive Valuementioning

confidence: 99%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.

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Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature

Liu,

Deng,

Guo

et al. 2023

Diagn Pathol

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Background The locally advanced cervical cancer (LACC) of FIGO stage IB3-IIA2 is characterized by large local mass, poor prognosis and survival rate. Tumor response to neoadjuvant chemotherapy for LACC, utilized as a surrogate endpoint, is urgently needed to improve. Given that the antitumor immune response can be suppressed by programed death-1 axis, the treatment paradigm of neoadjuvant chemotherapy combined with immunotherapy has been explored as one of the prognostic treatments in a variety of solid carcinoma. So far, the application of sintilimab, a domestic immune checkpoint inhibitor, combined with neoadjuvant chemotherapy is still limited in LACC, especially in large lesions. Case description We present three postmenopausal women diagnosed with FIGO stage IB3-IIA2 cervical squamous cell carcinoma with lesions larger than 5 cm. Demographic, clinical, histopathological, laboratory and imaging data were record. At the completion of the neoadjuvant therapy with paclitaxel plus carboplatin combined with sintilimab, all patients underwent hysterectomy. After neoadjuvant treatment, a pathologic complete response in case 1 and partial responses in case 2 and case 3 were achieved, and neither patient showed any relapse during the follow-up period of 16 to 22 months. Conclusions This report provide evidence to support the combination of sintilimab with neoadjuvant chemotherapy in cervical cancer, which has yet to be validated in prospective studies. More clinical data are needed to verify the effectiveness of the combined regimens. This literature review also collected studies involving potential predictors of response to NACT and immunotherapy, which would be helpful in stratifying patients for future trials.

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XPA expression is a predictive marker of the effectiveness of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

Cited by 4 publications

References 34 publications

XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

XPA serves as an autophagy and apoptosis inducer by suppressing hepatocellular carcinoma in a PI3K/Akt/mTOR dependent manner

XPA: DNA Repair Protein of Significant Clinical Importance

Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature

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