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PKM2 upregulation promotes malignancy and indicates poor prognosis for intrahepatic cholangiocarcinoma - 20/03/20

Doi : 10.1016/j.clinre.2019.06.008 
Ze Qian a, b, c, d, Wendi Hu a, b, c, d, Zhen Lv a, b, c, d, Hua Liu a, b, c, d, Diyu Chen a, b, c, d, Yacong Wang e, Jian Wu a, b, c, d, , Shusen Zheng a, b, c, d,
a Division of Hepatobiliary, Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China 
b Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, China 
c Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province, China 
d Collaborative innovation center for Diagnosis treatment of infectious diseases, Hangzhou, China 
e Department of Gerontology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China 

Corresponding authors at:Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang UniversityHangzhou 310003China

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Highlights

I wish to submit an original article for publication in Clinics and Research in Hepatology and Gastroenterology, titled “PKM2 upregulation diminishes malignancy and indicates good prognosis for intrahepatic cholangiocarcinoma”.
Although pyruvate kinase M2 (PKM2) has been shown to be among the crucial enzymes that regulate aerobic glycolysis in multiple tumor cells, its role in the treatment and prognosis of intrahepatic cholangiocarcinoma (ICC) remains unclear. This study aimed to determine whether the expression status of PKM2 is potentially associated with the clinical outcomes of ICC. We believe that our study makes a significant contribution to the literature because we provide clinical evidence of the impact of PKM2 in ICC, the oncogenesis of which is poorly understood. Our findings can help clinicians further understand the critical role of PKM2 in cancer cell growth that makes it a therapeutic target to improve patient prognosis.
Further, we believe that this paper will be of interest to the readership of your journal because our findings can be helpful in the development of novel molecular targets for ICC therapy.
This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All authors have contributed to, read and approved the final manuscript for submission. All study participants provided informed consent, and the study design was approved by the appropriate ethics review board.

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Summary

Background

Although pyruvate kinase M2 (PKM2) has been shown to be among the crucial enzymes that regulate aerobic glycolysis in multiple tumour cells, its role in the treatment and prognosis of intrahepatic cholangiocarcinoma (ICC) remains unclear. This study primarily aimed to determine whether the expression status of PKM2 is potentially associated with the clinical outcomes of ICC.

Methods

PKM2 expression was evaluated in ICC cell lines and tissues via real-time quantitative reverse-transcription polymerase chain reaction, immunofluorescence assays, and Western blot, and its prognostic value was determined according to its impact on the overall survival of patients.

Results

We found that PKM2 is highly expressed in ICC, and this was correlated with patient survival. Moreover, we found that PKM2 knockdown could considerably inhibit ICC cell proliferation, invasion, and migration in vitro.

Conclusions

PKM2 was overexpressed in ICC, and it may regulate proliferation, invasion, and migration and lead to poor prognosis. Thus, PKM2 might be a potential independent prognostic factor for ICC.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : Intrahepatic cholangiocarcinoma, Prognosis, Cell proliferation, Migration, Pyruvate kinase


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