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. 2021 Oct 11;10(20):4652.
doi: 10.3390/jcm10204652.

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin

Jung Won Chun  1 , Boyoung Lee  1 , Weon Seo Park  2 , Nayoung Han  1   2 , Eun Kyung Hong  1   2 , Eun Young Park  3 , Sung Sik Han  1 , Sang-Jae Park  1 , Tae Hyun Kim  1 , Woo Jin Lee  1 , Sang Myung Woo  1
Affiliations

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin

Jung Won Chun et al. J Clin Med. .

Abstract

The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in patients who treated with GP for advanced BTC. Tumor samples were obtained from 34 patients with unresectable or recurrent BTC who were treated with GP between August 2015 and February 2018. Intratumoral expression of hENT1, DCK, CDA and RRM1 was determined by immunohistochemistry and analyzed for association with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Median OS was significantly longer in the RRM1-negative group than in the RRM1-positive (9.9 months vs. 5.9 months, p = 0.037). Multivariate adjustment analyses also demonstrated RRM1 expression as an independent prognostic factor for OS in patients treated with GP chemotherapy. Increased intratumoral expression of RRM1 on immunohistochemical staining may be a biomarker predicting poor survival in patients with GP chemotherapy for advanced BTC. Large-scale well-predefined prospective research is needed to validate the utility of biomarkers in clinical practice.

Keywords: biliary tract neoplasms; cisplatin; gemcitabine; ribonucleotide reductases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical analysis of the intratumoral expression of proteins associated with gemcitabine transport and metabolism in patients with biliary tract cancers. (A) hENT1 in gallbladder (GB) cancer, (B) DCK in intrahepatic cholangiocarcinoma, (C) CDA in GB cancer, (D) RRM1 in GB cancer.
Figure 2
Figure 2
Kaplan–Meier analysis of the relationships of intratumoral expression of biomarkers with progression-free survival in patients with biliary tract cancers. (A) hENT1, (B) DCK, (C) CDA, (D) RRM1. hENT1, human equilibrative nucleoside transporter 1; DCK, deoxycytidine kinase; CDA, Cytidine deaminase; RRM1, ribonucleotide reductase subunit 1.
Figure 3
Figure 3
Kaplan–Meier analysis of the relationships of intratumoral expression of biomarkers with overall survival in patients with biliary tract cancers. (A) hENT1, (B) DCK, (C) CDA, (D) RRM1. hENT1, human equilibrative nucleoside transporter 1; DCK, deoxycytidine kinase; CDA, Cytidine deaminase; RRM1, ribonucleotide reductase subunit 1.
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References

    1. De Groen P.C., Gores G.J., LaRusso N.F., Gunderson L.L., Nagorney D.M. Biliary Tract Cancers. N. Engl. J. Med. 1999;341:1368–1378. doi: 10.1056/NEJM199910283411807. - DOI - PubMed
    1. Park J.O., Oh D.-Y., Hsu C., Chen J.-S., Chen L.-T., Orlando M., Kim J.S., Lim H.Y. Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review. Cancer Res. Treat. 2015;47:343–361. doi: 10.4143/crt.2014.308. - DOI - PMC - PubMed
    1. Tariq N.-U.-A., McNamara M.G., Valle J.W. Biliary tract cancers: Current knowledge, clinical candidates and future challenges. Cancer Manag. Res. 2019;11:2623–2642. doi: 10.2147/CMAR.S157092. - DOI - PMC - PubMed
    1. André T., Reyes-Vidal J.M., Fartoux L., Ross P., Leslie M., Rosmorduc O., Clemens M.R., Louvet C., Perez N., Mehmud F., et al. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: A phase II study. Br. J. Cancer. 2008;99:862–867. doi: 10.1038/sj.bjc.6604628. - DOI - PMC - PubMed
    1. Knox J.J., Hedley D., Oza A., Feld R., Siu L.L., Chen E., Nematollahi M., Pond G.R., Zhang J., Moore M.J. Combining Gemcitabine and Capecitabine in Patients With Advanced Biliary Cancer: A Phase II Trial. J. Clin. Oncol. 2005;23:2332–2338. doi: 10.1200/JCO.2005.51.008. - DOI - PubMed

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