Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment

Li, Hengchao; Di, Yang; Li, Ji; Jiang, Yongjian; He, Hang; Yao, Lie; Gu, Jichun; Lu, Jiajun; Song, Jia; Chen, Shiqing; Cai, Shangli; Jin, Chen; Yuan, Zhou; Fu, Deliang

doi:10.7150/jca.43087

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International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

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J Cancer 2020; 11(15):4316-4323. doi:10.7150/jca.43087 This issue Cite

Research Paper

Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment

Hengchao Li^1*, Yang Di^1*, Ji Li¹, Yongjian Jiang¹, Hang He¹, Lie Yao¹, Jichun Gu¹, Jiajun Lu², Jia Song³, Shiqing Chen³, Shangli Cai³, Chen Jin¹, Zhou Yuan^2✉, Deliang Fu^1✉

1. Department of Pancreatic Surgery, Huashan hospital, Fudan University, Shanghai, 200040, China.
2. Department of General Surgery, No.6 People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, China.
3. The Medical Department, 3D Medicines Inc., Shanghai, 201114, China
^*Co-First Author: these authors are equally to this work

Citation:

Li H, Di Y, Li J, Jiang Y, He H, Yao L, Gu J, Lu J, Song J, Chen S, Cai S, Jin C, Yuan Z, Fu D. Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment. J Cancer 2020; 11(15):4316-4323. doi:10.7150/jca.43087. https://www.jcancer.org/v11p4316.htm

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Abstract

Objective: Pancreatic cancer (PC) is a malignant tumor with limited therapeutic choices and extremely poor prognosis. Personalized therapy based on gene alternations is a promising choice. Considering tumor heterogeneity, the practice of ctDNA analysis has drawn the attention. Here, we try to assess the applicability of ctDNA in PC.

Methods and materials: Next generation sequencing (NGS) was performed from blood samples of 223 PC patients and tissue sample of 564 PC patients. Genomic data from the TCGA database were also utilized. In addition, two cases received personalized treatment based on ctDNA sequencing results were reported.

Results: Based on ctDNA sequencing, the genomic features of PC was revealed. Totally, 68.2% of patients detected at least one reportable genomic alteration (GA) from ctDNA. The frequently altered genes were KRAS (53.5%), followed by TP53 (52.8%), and CDKN2A (15.1%). Cell cycle control (8%) and DNA damage response (8%) pathways enriched the most mutated genes. Compared with mutations from tissue samples and a tissue-genomic database, similar frequencies of GAs were detected from ctDNA. The first two highest frequent mutation of genes were the same, but some of mutated genes were inclined to be observed in ctDNA, like AR. And two cases who received personalized therapy achieved better clinical benefit.

Conclusion: Blood-source ctDNA sequencing could be regarded as a meaningful complement to tissue testing, and might guide clinically therapeutic regimen.

Keywords: Pancreatic cancer, Circulating tumor DNA, Sequencing, Genomic feature, Personalized therapy

Citation styles

APA

Li, H., Di, Y., Li, J., Jiang, Y., He, H., Yao, L., Gu, J., Lu, J., Song, J., Chen, S., Cai, S., Jin, C., Yuan, Z., Fu, D. (2020). Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment. Journal of Cancer, 11(15), 4316-4323. https://doi.org/10.7150/jca.43087.

ACS

Li, H.; Di, Y.; Li, J.; Jiang, Y.; He, H.; Yao, L.; Gu, J.; Lu, J.; Song, J.; Chen, S.; Cai, S.; Jin, C.; Yuan, Z.; Fu, D. Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment. J. Cancer 2020, 11 (15), 4316-4323. DOI: 10.7150/jca.43087.

NLM

CSE

Li H, Di Y, Li J, Jiang Y, He H, Yao L, Gu J, Lu J, Song J, Chen S, Cai S, Jin C, Yuan Z, Fu D. 2020. Blood-based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Pancreatic Cancer and its Value to Guide Clinical Treatment. J Cancer. 11(15):4316-4323.

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