Literature DB >> 29556276

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

Takuma Wada1,2, Takeshi Fukuda1, Masahiro Shimomura1, Yuta Inoue1, Masaru Kawanishi1, Reiko Tasaka1, Tomoyo Yasui1, Kazuo Ikeda2, Toshiyuki Sumi1.   

Abstract

The standard treatment for locally advanced uterine cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) may reduce tumor size and facilitate a hysterectomy, thereby improving the prognosis for patients with locally advanced cervical cancer. In contrast, unsuccessful NAC may worsen the prognosis because if a hysterectomy is not possible, the change in treatment plan may delay the initiation of core treatment. Therefore, there is a need to identify biomarkers that predict the efficacy of NAC in patients with uterine cervical cancer. The xeroderma pigmentosum complementation group A (XPA) protein serves a major role in nucleotide excision repair, which is a key DNA damage response pathway involved in cisplatin resistance. In the present study, the association between XPA expression in tumor tissue and the efficacy of NAC for locally advanced uterine cervical cancer was investigated. Data from 56 patients aged <70 years with locally advanced uterine cervical cancer (FIGO stages IIIA or IIIB) who were classified into two groups based on effective (n=31) and ineffective (n=25) responses to NAC treatment was evaluated. Tumor tissue samples were obtained by punch biopsy prior to NAC and XPA expression was examined immunohistochemically and scored using a weighted scoring system. In addition, the effects of RNA interference-mediated downregulation of XPA on the cisplatin sensitivity of uterine cervical cancer cells was investigated in vitro. It was revealed that the NAC effective group had significantly lower weighted XPA scores than the NAC ineffective group (P=0.001). Similarly, low tumor expression of XPA was significantly associated with higher sensitivity to NAC (P=0.001). Additionally, the downregulation of XPA expression in cervical cancer cells significantly increased their sensitivity to cisplatin in vitro. The results of the present study suggest that low XPA expression may be a predictive biomarker of NAC efficacy for patients with locally advanced uterine cervical cancer, which may be helpful for improving their prognosis.

Entities:  

Keywords:  neoadjuvant chemotherapy; platinum resistance; predictive marker; uterine cervical cancer; xeroderma pigmentosum complementation group A

Year:  2018        PMID: 29556276      PMCID: PMC5844067          DOI: 10.3892/ol.2018.7810

Source DB:  PubMed          Journal:  Oncol Lett        ISSN: 1792-1074            Impact factor:   2.967


  34 in total

1.  Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.

Authors:  Ran-Yi Liu; Zizheng Dong; Jianguo Liu; Ling Zhou; Wenlin Huang; Sok Kean Khoo; Zhongfa Zhang; David Petillo; Bin Tean Teh; Chao-Nan Qian; Jian-Ting Zhang
Journal:  Mol Cancer Ther       Date:  2013-08-16       Impact factor: 6.261

2.  Cooperative interaction of human XPA stabilizes and enhances specific binding of XPA to DNA damage.

Authors:  Yu Liu; Yiyong Liu; Zhengguan Yang; Christopher Utzat; Guizhi Wang; Ashis K Basu; Yue Zou
Journal:  Biochemistry       Date:  2005-05-17       Impact factor: 3.162

3.  DNA repair capacity and cisplatin sensitivity of human testis tumour cells.

Authors:  B Köberle; K A Grimaldi; A Sunters; J A Hartley; L R Kelland; J R Masters
Journal:  Int J Cancer       Date:  1997-03-04       Impact factor: 7.396

Review 4.  Cellular processing of platinum anticancer drugs.

Authors:  Dong Wang; Stephen J Lippard
Journal:  Nat Rev Drug Discov       Date:  2005-04       Impact factor: 84.694

5.  Balloon-occluded arterial infusion chemotherapy, simple total hysterectomy, and radiotherapy as a useful combination-therapy for advanced cancer of the uterine cervix.

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Journal:  Oncol Rep       Date:  2000 Jan-Feb       Impact factor: 3.906

6.  Association of HPV infection with prognosis after neoadjuvant chemotherapy in advanced uterine cervical cancer.

Authors:  Hiroyuki Nobeyama; Toshiyuki Sumi; Fumiko Misugi; Eri Okamoto; Kanae Hattori; Yoshinari Matsumoto; Tomoyo Yasui; Ken-ichi Honda; Kazuhiro Iwai; Osamu Ishiko
Journal:  Int J Mol Med       Date:  2004-07       Impact factor: 4.101

7.  Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01.

Authors:  Patricia J Eifel; Kathryn Winter; Mitchell Morris; Charles Levenback; Perry W Grigsby; Jay Cooper; Marvin Rotman; David Gershenson; David G Mutch
Journal:  J Clin Oncol       Date:  2004-03-01       Impact factor: 44.544

8.  Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.

Authors:  M H Tattersall; V Lorvidhaya; V Vootiprux; A Cheirsilpa; F Wong; T Azhar; H P Lee; S B Kang; A Manalo; M S Yen
Journal:  J Clin Oncol       Date:  1995-02       Impact factor: 44.544

Review 9.  Platinum resistance: the role of DNA repair pathways.

Authors:  Lainie P Martin; Thomas C Hamilton; Russell J Schilder
Journal:  Clin Cancer Res       Date:  2008-03-01       Impact factor: 12.531

10.  Retaining MKP1 expression and attenuating JNK-mediated apoptosis by RIP1 for cisplatin resistance through miR-940 inhibition.

Authors:  Qiong Wang; Shaoqing Shi; Weiyang He; Mabel T Padilla; Lin Zhang; Xia Wang; Bin Zhang; Yong Lin
Journal:  Oncotarget       Date:  2014-03-15
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  2 in total

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

Authors:  Yi Deng; Qing-Song Chen; Wei-Feng Huang; Jiang-Wen Dai; Zhong-Jun Wu
Journal:  J Gastrointest Oncol       Date:  2021-08

Review 2.  XPA: DNA Repair Protein of Significant Clinical Importance.

Authors:  Lucia Borszéková Pulzová; Thomas A Ward; Miroslav Chovanec
Journal:  Int J Mol Sci       Date:  2020-03-22       Impact factor: 5.923

  2 in total

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