Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutate...
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-07-01
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| Series: | Open Life Sciences |
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| Online Access: | https://doi.org/10.1515/biol-2022-0652 |
| _version_ | 1797773510299353088 |
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| author | Peng Jianbo Fang Shuo Li Meisheng Liu Yuxin Liang Xiaolu Li Zuobiao Chen Gaohui Peng Lijiao Chen Nianping Liu Lei Xu Xiaohong Dai Wei |
| author_facet | Peng Jianbo Fang Shuo Li Meisheng Liu Yuxin Liang Xiaolu Li Zuobiao Chen Gaohui Peng Lijiao Chen Nianping Liu Lei Xu Xiaohong Dai Wei |
| author_sort | Peng Jianbo |
| collection | DOAJ |
| description | The aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0–36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients. |
| first_indexed | 2024-03-12T22:07:34Z |
| format | Article |
| id | doaj.art-e6aa7947c8264cc685eb4d7c789239ff |
| institution | Directory Open Access Journal |
| issn | 2391-5412 |
| language | English |
| last_indexed | 2024-03-12T22:07:34Z |
| publishDate | 2023-07-01 |
| publisher | De Gruyter |
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| series | Open Life Sciences |
| spelling | doaj.art-e6aa7947c8264cc685eb4d7c789239ff2023-07-24T11:18:21ZengDe GruyterOpen Life Sciences2391-54122023-07-0118126223210.1515/biol-2022-0652Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosisPeng Jianbo0Fang Shuo1Li Meisheng2Liu Yuxin3Liang Xiaolu4Li Zuobiao5Chen Gaohui6Peng Lijiao7Chen Nianping8Liu Lei9Xu Xiaohong10Dai Wei11Foshan Traditional Chinese Medicine Hospital, Guangdong, 518000, ChinaDepartment of Oncology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518000, ChinaFoshan First People’s Hospital, Guangdong, 518000, ChinaGuangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaGuangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Ultrasound, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524000, ChinaThe aim of this study is to investigate certain genetic features of intrahepatic cholangiocarcinoma (ICCA). A total of 12 eligible ICCA patients were enrolled, and tumor tissues from the patients were subjected to next-generation sequencing of a multi-genes panel. Tumor mutation burden (TMB), mutated genes, copy number variants (CNVs), and pathway enrichment analysis were performed. The median TMB was 2.76 Mutation/Mb (range, 0–36.62 Mutation/Mb) in ICCA patients. The top two most commonly mutated genes in ICCA were KRAS (33%) and TP53 (25%). The co-mutations of KRAS and TP53 were 16.7% (2/12) in ICCA patients. Notably, patient P6 with the highest TMB did not have KRAS and TP53 mutations. Additionally, TP53 and/or KRAS alterations were significantly associated with poor progression-free survival than those with wild type (1.4 months vs 18 months). DNA damage repair and homologs recombinant repair deficiencies were significantly associated with high TMB in ICCA cases. In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in ICCA patients.https://doi.org/10.1515/biol-2022-0652intrahepatic cholangiocarcinomanext-generation sequencinggenetic profiletumor mutation burdenprognosis analysis |
| spellingShingle | Peng Jianbo Fang Shuo Li Meisheng Liu Yuxin Liang Xiaolu Li Zuobiao Chen Gaohui Peng Lijiao Chen Nianping Liu Lei Xu Xiaohong Dai Wei Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis Open Life Sciences intrahepatic cholangiocarcinoma next-generation sequencing genetic profile tumor mutation burden prognosis analysis |
| title | Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| title_full | Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| title_fullStr | Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| title_full_unstemmed | Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| title_short | Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| title_sort | genetic alterations of kras and tp53 in intrahepatic cholangiocarcinoma associated with poor prognosis |
| topic | intrahepatic cholangiocarcinoma next-generation sequencing genetic profile tumor mutation burden prognosis analysis |
| url | https://doi.org/10.1515/biol-2022-0652 |
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