Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas
Abstract Background Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses. Methods We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to anal...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-07-01
|
| Series: | Biomarker Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40364-023-00492-7 |
| _version_ | 1797784523926142976 |
|---|---|
| author | Ya-Sian Chang Siang-Jyun Tu Hong-Da Chen Chin-Chun Chung Ming-Hon Hsu Yu-Pao Chou Ya-Ting Lee Ju-Chen Yen Long-Bin Jeng Jan-Gowth Chang |
| author_facet | Ya-Sian Chang Siang-Jyun Tu Hong-Da Chen Chin-Chun Chung Ming-Hon Hsu Yu-Pao Chou Ya-Ting Lee Ju-Chen Yen Long-Bin Jeng Jan-Gowth Chang |
| author_sort | Ya-Sian Chang |
| collection | DOAJ |
| description | Abstract Background Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses. Methods We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence. Results The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment. Conclusions This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC. |
| first_indexed | 2024-03-13T00:41:07Z |
| format | Article |
| id | doaj.art-e6c619f4454742de97b466450d125919 |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-03-13T00:41:07Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-e6c619f4454742de97b466450d1259192023-07-09T11:20:07ZengBMCBiomarker Research2050-77712023-07-0111111210.1186/s40364-023-00492-7Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomasYa-Sian Chang0Siang-Jyun Tu1Hong-Da Chen2Chin-Chun Chung3Ming-Hon Hsu4Yu-Pao Chou5Ya-Ting Lee6Ju-Chen Yen7Long-Bin Jeng8Jan-Gowth Chang9Center for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalOrgan Transplantation Center, China Medical University HospitalCenter for Precision Medicine, China Medical University HospitalAbstract Background Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses. Methods We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence. Results The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment. Conclusions This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.https://doi.org/10.1186/s40364-023-00492-7Whole genome sequencingRNA sequencingTaiwanese HCCAlternative splicingImmune checkpoint geneTumor microenvironment |
| spellingShingle | Ya-Sian Chang Siang-Jyun Tu Hong-Da Chen Chin-Chun Chung Ming-Hon Hsu Yu-Pao Chou Ya-Ting Lee Ju-Chen Yen Long-Bin Jeng Jan-Gowth Chang Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas Biomarker Research Whole genome sequencing RNA sequencing Taiwanese HCC Alternative splicing Immune checkpoint gene Tumor microenvironment |
| title | Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas |
| title_full | Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas |
| title_fullStr | Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas |
| title_full_unstemmed | Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas |
| title_short | Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas |
| title_sort | whole genome and rna sequencing analyses for 254 taiwanese hepatocellular carcinomas |
| topic | Whole genome sequencing RNA sequencing Taiwanese HCC Alternative splicing Immune checkpoint gene Tumor microenvironment |
| url | https://doi.org/10.1186/s40364-023-00492-7 |
| work_keys_str_mv | AT yasianchang wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT siangjyuntu wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT hongdachen wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT chinchunchung wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT minghonhsu wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT yupaochou wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT yatinglee wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT juchenyen wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT longbinjeng wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas AT jangowthchang wholegenomeandrnasequencinganalysesfor254taiwanesehepatocellularcarcinomas |