Characterization of pancreatic cancer with ultra-low tumor mutational burden
Abstract In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-31579-8 |
| _version_ | 1827984360662368256 |
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| author | Taisuke Imamura Ryo Ashida Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Keiichi Hatakeyama Takeshi Nagashima Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi |
| author_facet | Taisuke Imamura Ryo Ashida Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Keiichi Hatakeyama Takeshi Nagashima Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi |
| author_sort | Taisuke Imamura |
| collection | DOAJ |
| description | Abstract In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (< 5.0, ≥ 1.0), or Ultra-low (< 1.0). Nineteen samples (20%) were classified as TMB-low, and 74 (80%) were classified as TMB-ultra-low; no samples were TMB-high. TMB-ultra-low PC had significantly fewer borderline resectable lesions (P = 0.028) and fewer adenosquamous carcinomas (P = 0.003) than TBM-low PC. Furthermore, the TMB-ultra-low PC showed significantly lower detection rates of driver mutations and copy number variations. Microsatellite instability was not significantly correlated with the TMB status. The TMB-ultra-low PC had a significantly better prognosis than TBM-low PC (P = 0.023). A multivariate analysis identified TMB-ultra-low PC as an independent favorable prognostic factor (hazard ratio, 2.11; P = 0.019). A gene expression analysis showed that TMB-ultra-low PC was associated with reduced TP53 inactivation (P = 0.003) and reduced chromosomal instability (P = 0.001) compared to TBM-low PC. TMB-ultra-low PC had specific gene expression signatures and a better prognosis than TMB-low PC. |
| first_indexed | 2024-04-09T22:59:04Z |
| format | Article |
| id | doaj.art-185d8dbe29404cfab80d48a8d53a6de5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:59:04Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-185d8dbe29404cfab80d48a8d53a6de52023-03-22T11:04:36ZengNature PortfolioScientific Reports2045-23222023-03-0113111210.1038/s41598-023-31579-8Characterization of pancreatic cancer with ultra-low tumor mutational burdenTaisuke Imamura0Ryo Ashida1Keiichi Ohshima2Katsuhiko Uesaka3Teiichi Sugiura4Katsuhisa Ohgi5Mihoko Yamada6Shimpei Otsuka7Keiichi Hatakeyama8Takeshi Nagashima9Takashi Sugino10Kenichi Urakami11Yasuto Akiyama12Ken Yamaguchi13Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterMedical Genetics Division, Shizuoka Cancer Center Research InstituteDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterDivision of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer CenterCancer Multiomics Division, Shizuoka Cancer Center Research InstituteCancer Diagnostics Research Division, Shizuoka Cancer Center Research InstituteDivision of Pathology, Shizuoka Cancer CenterCancer Diagnostics Research Division, Shizuoka Cancer Center Research InstituteImmunotherapy Division, Shizuoka Cancer Center Research InstituteShizuoka Cancer Center Hospital and Research InstituteAbstract In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (< 5.0, ≥ 1.0), or Ultra-low (< 1.0). Nineteen samples (20%) were classified as TMB-low, and 74 (80%) were classified as TMB-ultra-low; no samples were TMB-high. TMB-ultra-low PC had significantly fewer borderline resectable lesions (P = 0.028) and fewer adenosquamous carcinomas (P = 0.003) than TBM-low PC. Furthermore, the TMB-ultra-low PC showed significantly lower detection rates of driver mutations and copy number variations. Microsatellite instability was not significantly correlated with the TMB status. The TMB-ultra-low PC had a significantly better prognosis than TBM-low PC (P = 0.023). A multivariate analysis identified TMB-ultra-low PC as an independent favorable prognostic factor (hazard ratio, 2.11; P = 0.019). A gene expression analysis showed that TMB-ultra-low PC was associated with reduced TP53 inactivation (P = 0.003) and reduced chromosomal instability (P = 0.001) compared to TBM-low PC. TMB-ultra-low PC had specific gene expression signatures and a better prognosis than TMB-low PC.https://doi.org/10.1038/s41598-023-31579-8 |
| spellingShingle | Taisuke Imamura Ryo Ashida Keiichi Ohshima Katsuhiko Uesaka Teiichi Sugiura Katsuhisa Ohgi Mihoko Yamada Shimpei Otsuka Keiichi Hatakeyama Takeshi Nagashima Takashi Sugino Kenichi Urakami Yasuto Akiyama Ken Yamaguchi Characterization of pancreatic cancer with ultra-low tumor mutational burden Scientific Reports |
| title | Characterization of pancreatic cancer with ultra-low tumor mutational burden |
| title_full | Characterization of pancreatic cancer with ultra-low tumor mutational burden |
| title_fullStr | Characterization of pancreatic cancer with ultra-low tumor mutational burden |
| title_full_unstemmed | Characterization of pancreatic cancer with ultra-low tumor mutational burden |
| title_short | Characterization of pancreatic cancer with ultra-low tumor mutational burden |
| title_sort | characterization of pancreatic cancer with ultra low tumor mutational burden |
| url | https://doi.org/10.1038/s41598-023-31579-8 |
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