Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma
Abstract Background The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels. Methods Here we first characterized the influencing factors of pro...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-022-02496-3 |
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| author | Zhiqiang Li Hongqiang Gao Xiang Zhang Qiyu Liu Gang Chen |
| author_facet | Zhiqiang Li Hongqiang Gao Xiang Zhang Qiyu Liu Gang Chen |
| author_sort | Zhiqiang Li |
| collection | DOAJ |
| description | Abstract Background The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels. Methods Here we first characterized the influencing factors of prognosis of stage I HCC patients by downloading and analyzing the whole-exome somatic mutation data, messenger ribonucleic acid (mRNA) transcription data, along with demographic and clinical information of 163 stage I HCC patients from the TCGA database. The relationship between the influencing factors and HCC prognosis was studied in detail, and a prediction Nomogram model was established. Figures and tables were plotted using the R software. Results TP53, CTNNB1, TTN, MUC16 and ALB were the top mutated genes in stage I HCC. A series of co-mutations and mutually exclusive mutations were identified. Twenty-nine genes with significant stratification on prognosis were identified, including highly mutated LRP1B, ARID1A and PTPRQ. Patients with wild type (WT) genes unanimously exhibited significantly better overall survival rate than those with mutants. Patients with the top 10% tumor mutational burden (TMB) exhibited significantly worse prognosis than the rest 90%. Further characterization of transcriptional profile revealed that membrane functions, cell skeleton proteins, ion channels, receptor function and cell cycle were comprehensively altered in stage I HCC. Univariate and multivariate analyses were performed at clinicopathological, mutational and transcriptional levels. The combined analysis revealed sex, race, TMB, neoplasm histologic grade, Child–Pugh grade, MMRN1, OXT and COX6A2 transcription as independent risk factors. These factors were used to establish a Nomogram model to predict the prognosis of individual HCC patients. Conclusions The influencing factors of prognosis of stage I HCC have been characterized for the first time at clinicopathological, mutational and transcriptional levels. A Nomogram model has been established to predict the prognosis. Further validation is needed to confirm the effectiveness and reliability of the model. |
| first_indexed | 2024-04-14T07:18:00Z |
| format | Article |
| id | doaj.art-6ae8f2828dae4557b36fc37e1433c007 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-14T07:18:00Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-6ae8f2828dae4557b36fc37e1433c0072022-12-22T02:06:16ZengBMCBMC Gastroenterology1471-230X2022-09-0122111310.1186/s12876-022-02496-3Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinomaZhiqiang Li0Hongqiang Gao1Xiang Zhang2Qiyu Liu3Gang Chen4Department of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of KunmingDepartment of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of KunmingDepartment of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of KunmingDepartment of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of KunmingDepartment of Hepatobiliary Pancreatic Surgery, The First People’s Hospital of KunmingAbstract Background The prognosis of hepatocellular carcinoma (HCC) has been extensively studied. However, the impact on prognosis of stage I HCC has not been well studied at clincopathological, mutational and transcriptional levels. Methods Here we first characterized the influencing factors of prognosis of stage I HCC patients by downloading and analyzing the whole-exome somatic mutation data, messenger ribonucleic acid (mRNA) transcription data, along with demographic and clinical information of 163 stage I HCC patients from the TCGA database. The relationship between the influencing factors and HCC prognosis was studied in detail, and a prediction Nomogram model was established. Figures and tables were plotted using the R software. Results TP53, CTNNB1, TTN, MUC16 and ALB were the top mutated genes in stage I HCC. A series of co-mutations and mutually exclusive mutations were identified. Twenty-nine genes with significant stratification on prognosis were identified, including highly mutated LRP1B, ARID1A and PTPRQ. Patients with wild type (WT) genes unanimously exhibited significantly better overall survival rate than those with mutants. Patients with the top 10% tumor mutational burden (TMB) exhibited significantly worse prognosis than the rest 90%. Further characterization of transcriptional profile revealed that membrane functions, cell skeleton proteins, ion channels, receptor function and cell cycle were comprehensively altered in stage I HCC. Univariate and multivariate analyses were performed at clinicopathological, mutational and transcriptional levels. The combined analysis revealed sex, race, TMB, neoplasm histologic grade, Child–Pugh grade, MMRN1, OXT and COX6A2 transcription as independent risk factors. These factors were used to establish a Nomogram model to predict the prognosis of individual HCC patients. Conclusions The influencing factors of prognosis of stage I HCC have been characterized for the first time at clinicopathological, mutational and transcriptional levels. A Nomogram model has been established to predict the prognosis. Further validation is needed to confirm the effectiveness and reliability of the model.https://doi.org/10.1186/s12876-022-02496-3Hepatocellular carcinomaHCCMutationTranscriptionPrognosisSurgery |
| spellingShingle | Zhiqiang Li Hongqiang Gao Xiang Zhang Qiyu Liu Gang Chen Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma BMC Gastroenterology Hepatocellular carcinoma HCC Mutation Transcription Prognosis Surgery |
| title | Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma |
| title_full | Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma |
| title_fullStr | Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma |
| title_full_unstemmed | Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma |
| title_short | Mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage I hepatocellular carcinoma |
| title_sort | mutational and transcriptional alterations and clinicopathological factors predict the prognosis of stage i hepatocellular carcinoma |
| topic | Hepatocellular carcinoma HCC Mutation Transcription Prognosis Surgery |
| url | https://doi.org/10.1186/s12876-022-02496-3 |
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