High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients
Abstract Background Microsatellite instability (MSI) is a well-established predictive biomarker for immune checkpoint inhibitor (ICI) response in metastatic colon cancer. Both high MSI and tumor mutational burden (TMB) are markers of genomic instability. However, the prognostic and predictive value...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05927-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544341590376448 |
|---|---|
| author | Annabella Di Mauro Mariachiara Santorsola Giovanni Savarese Roberto Sirica Monica Ianniello Alessia Maria Cossu Anna Ceccarelli Francesco Sabbatino Marco Bocchetti Anna Chiara Carratù Francesca Pentimalli Gerardo Ferrara Guglielmo Nasti Michele Caraglia Alessandro Ottaiano |
| author_facet | Annabella Di Mauro Mariachiara Santorsola Giovanni Savarese Roberto Sirica Monica Ianniello Alessia Maria Cossu Anna Ceccarelli Francesco Sabbatino Marco Bocchetti Anna Chiara Carratù Francesca Pentimalli Gerardo Ferrara Guglielmo Nasti Michele Caraglia Alessandro Ottaiano |
| author_sort | Annabella Di Mauro |
| collection | DOAJ |
| description | Abstract Background Microsatellite instability (MSI) is a well-established predictive biomarker for immune checkpoint inhibitor (ICI) response in metastatic colon cancer. Both high MSI and tumor mutational burden (TMB) are markers of genomic instability. However, the prognostic and predictive value of TMB in patients with microsatellite stable (MSS) tumors remains unclear. Methods We evaluated the prognostic significance of TMB levels in MSS metastatic colon cancer patients undergoing standard treatments. Tumor responses were assessed using RECIST v1.1 criteria. Comprehensive clinical and molecular profiling was conducted, including next-generation sequencing (NGS) for TMB evaluation with the TruSight Oncology® kit. Overall survival (OS) was the primary endpoint. Multivariate Cox regression analysis was utilized to assess the relationship among potential prognostic factors. Results Among 102 MSS metastatic colon cancer patients, high TMB (> 10 mut/mb) was associated with a significantly longer median OS compared to low TMB (70.0 vs 45.0 months, respectively; HR: 0.45; 95% CIs 0.21 to 0.96; P = 0.0396). Multivariate analysis, adjusting for age, gender, number of metastatic sites, response to first-line chemotherapy, RAS mutational status, and liver involvement, identified TMB as an independent prognostic factor, along with response to first-line chemotherapy. Conclusions Our results highlight the prognostic significance of TMB in MSS metastatic colon cancer patients, suggesting its potential role in patient stratification and treatment decision-making. |
| format | Article |
| id | doaj-art-2511af399ba9499ab479b1e841ab980d |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-2511af399ba9499ab479b1e841ab980d2025-01-12T12:37:29ZengBMCJournal of Translational Medicine1479-58762024-12-0122111110.1186/s12967-024-05927-9High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patientsAnnabella Di Mauro0Mariachiara Santorsola1Giovanni Savarese2Roberto Sirica3Monica Ianniello4Alessia Maria Cossu5Anna Ceccarelli6Francesco Sabbatino7Marco Bocchetti8Anna Chiara Carratù9Francesca Pentimalli10Gerardo Ferrara11Guglielmo Nasti12Michele Caraglia13Alessandro Ottaiano14Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”Structure of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”AMES, Centro Polidiagnostico Strumentale SrlAMES, Centro Polidiagnostico Strumentale SrlAMES, Centro Polidiagnostico Strumentale SrlDepartment of Precision Medicine, University of Campania “L. Vanvitelli”Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica del Sacro CuoreDepartment of Medicine, Surgery and Dentistry, University of SalernoDepartment of Precision Medicine, University of Campania “L. Vanvitelli”Structure of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”Department of Medicine and Surgery, LUM University “Giuseppe Degennaro”Pathology Unit, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”Structure of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”Department of Precision Medicine, University of Campania “L. Vanvitelli”Structure of Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”Abstract Background Microsatellite instability (MSI) is a well-established predictive biomarker for immune checkpoint inhibitor (ICI) response in metastatic colon cancer. Both high MSI and tumor mutational burden (TMB) are markers of genomic instability. However, the prognostic and predictive value of TMB in patients with microsatellite stable (MSS) tumors remains unclear. Methods We evaluated the prognostic significance of TMB levels in MSS metastatic colon cancer patients undergoing standard treatments. Tumor responses were assessed using RECIST v1.1 criteria. Comprehensive clinical and molecular profiling was conducted, including next-generation sequencing (NGS) for TMB evaluation with the TruSight Oncology® kit. Overall survival (OS) was the primary endpoint. Multivariate Cox regression analysis was utilized to assess the relationship among potential prognostic factors. Results Among 102 MSS metastatic colon cancer patients, high TMB (> 10 mut/mb) was associated with a significantly longer median OS compared to low TMB (70.0 vs 45.0 months, respectively; HR: 0.45; 95% CIs 0.21 to 0.96; P = 0.0396). Multivariate analysis, adjusting for age, gender, number of metastatic sites, response to first-line chemotherapy, RAS mutational status, and liver involvement, identified TMB as an independent prognostic factor, along with response to first-line chemotherapy. Conclusions Our results highlight the prognostic significance of TMB in MSS metastatic colon cancer patients, suggesting its potential role in patient stratification and treatment decision-making.https://doi.org/10.1186/s12967-024-05927-9Microsatellite instabilityTumor mutational burdenColon cancerPrognosisNGS |
| spellingShingle | Annabella Di Mauro Mariachiara Santorsola Giovanni Savarese Roberto Sirica Monica Ianniello Alessia Maria Cossu Anna Ceccarelli Francesco Sabbatino Marco Bocchetti Anna Chiara Carratù Francesca Pentimalli Gerardo Ferrara Guglielmo Nasti Michele Caraglia Alessandro Ottaiano High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients Journal of Translational Medicine Microsatellite instability Tumor mutational burden Colon cancer Prognosis NGS |
| title | High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| title_full | High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| title_fullStr | High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| title_full_unstemmed | High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| title_short | High tumor mutational burden assessed through next-generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| title_sort | high tumor mutational burden assessed through next generation sequencing predicts favorable survival in microsatellite stable metastatic colon cancer patients |
| topic | Microsatellite instability Tumor mutational burden Colon cancer Prognosis NGS |
| url | https://doi.org/10.1186/s12967-024-05927-9 |
| work_keys_str_mv | AT annabelladimauro hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT mariachiarasantorsola hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT giovannisavarese hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT robertosirica hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT monicaianniello hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT alessiamariacossu hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT annaceccarelli hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT francescosabbatino hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT marcobocchetti hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT annachiaracarratu hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT francescapentimalli hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT gerardoferrara hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT guglielmonasti hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT michelecaraglia hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients AT alessandroottaiano hightumormutationalburdenassessedthroughnextgenerationsequencingpredictsfavorablesurvivalinmicrosatellitestablemetastaticcoloncancerpatients |