Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma
Mutational profiling of patients’ tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages...
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2709 |
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| author | Wen-Lang Fan Lan-Yan Yang Jason Chia-Hsun Hsieh Tsung-Chieh Lin Mei-Yeh Jade Lu Chun-Ta Liao |
| author_facet | Wen-Lang Fan Lan-Yan Yang Jason Chia-Hsun Hsieh Tsung-Chieh Lin Mei-Yeh Jade Lu Chun-Ta Liao |
| author_sort | Wen-Lang Fan |
| collection | DOAJ |
| description | Mutational profiling of patients’ tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (<i>p</i> = 0.0005) and overall survival (<i>p</i> = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (<i>p</i> = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy. |
| first_indexed | 2024-03-10T10:52:06Z |
| format | Article |
| id | doaj.art-d1b5804666b24c6a94b7f6f8f5db00d3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:52:06Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d1b5804666b24c6a94b7f6f8f5db00d32023-11-21T22:08:59ZengMDPI AGCancers2072-66942021-05-011311270910.3390/cancers13112709Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell CarcinomaWen-Lang Fan0Lan-Yan Yang1Jason Chia-Hsun Hsieh2Tsung-Chieh Lin3Mei-Yeh Jade Lu4Chun-Ta Liao5Genomic Medicine Core Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan 33382, TaiwanClinical Trial Center, Biostatistics and Informatics Unit, Linkou Chang Gung Memorial Hospital, Taoyuan 33382, TaiwanDepartment of Internal Medicine, Division of Hematology-Oncology, New Taipei Municipal TuCheng Hospital, New Taipei City 236043, TaiwanGenomic Medicine Core Laboratory, Linkou Chang Gung Memorial Hospital, Taoyuan 33382, TaiwanBiodiversity Research Center, Academia Sinica, Taipei 11529, TaiwanDepartment of Otorhinolaryngology, Head and Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan 33382, TaiwanMutational profiling of patients’ tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (<i>p</i> = 0.0005) and overall survival (<i>p</i> = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (<i>p</i> = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy.https://www.mdpi.com/2072-6694/13/11/2709oral cavity squamous cell carcinomaoncogenic signaling pathwaypathway instabilitymutational signaturesdisease-free survivaloverall survival |
| spellingShingle | Wen-Lang Fan Lan-Yan Yang Jason Chia-Hsun Hsieh Tsung-Chieh Lin Mei-Yeh Jade Lu Chun-Ta Liao Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma Cancers oral cavity squamous cell carcinoma oncogenic signaling pathway pathway instability mutational signatures disease-free survival overall survival |
| title | Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma |
| title_full | Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma |
| title_fullStr | Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma |
| title_full_unstemmed | Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma |
| title_short | Prognostic Genetic Biomarkers Based on Oncogenic Signaling Pathways for Outcome Prediction in Patients with Oral Cavity Squamous Cell Carcinoma |
| title_sort | prognostic genetic biomarkers based on oncogenic signaling pathways for outcome prediction in patients with oral cavity squamous cell carcinoma |
| topic | oral cavity squamous cell carcinoma oncogenic signaling pathway pathway instability mutational signatures disease-free survival overall survival |
| url | https://www.mdpi.com/2072-6694/13/11/2709 |
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