YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma
Abstract Background Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods To identif...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-03-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2761 |
| _version_ | 1797319222977626112 |
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| author | Honghai Dai Yang W. Shao Xiaoling Tong Xue Wu Jiaohui Pang Alei Feng Zhe Yang |
| author_facet | Honghai Dai Yang W. Shao Xiaoling Tong Xue Wu Jiaohui Pang Alei Feng Zhe Yang |
| author_sort | Honghai Dai |
| collection | DOAJ |
| description | Abstract Background Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods To identify prognostic biomarkers, we performed targeted next‐generation sequencing of 416 cancer‐related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) was analyzed. Results TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08‐0.77, P = .015) and progression‐free survival (PFS) (HR, 0.35; 95%CI, 0.13‐0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26‐13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95‐8.17, P = .062). In a subgroup analysis, while sex and M‐stage were controlled, a much stronger negative effect of YAP1 amplification vs wild‐type in LRFS was observed (log‐rank P = .0067). Conclusion The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored. |
| first_indexed | 2024-03-08T04:03:43Z |
| format | Article |
| id | doaj.art-82f575617bb74847a7df75ef503fce94 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T04:03:43Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-82f575617bb74847a7df75ef503fce942024-02-09T09:26:02ZengWileyCancer Medicine2045-76342020-03-01951628163710.1002/cam4.2761YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinomaHonghai Dai0Yang W. Shao1Xiaoling Tong2Xue Wu3Jiaohui Pang4Alei Feng5Zhe Yang6Tumor Research and Therapy Center Shandong Provincial Hospital Affiliated to Shandong University Jinan ChinaNanjing Geneseeq Technology Inc Nanjing ChinaTranslational Medicine Research Institute Geneseeq Technology Inc Toronto Ontario CanadaTranslational Medicine Research Institute Geneseeq Technology Inc Toronto Ontario CanadaNanjing Geneseeq Technology Inc Nanjing ChinaTumor Research and Therapy Center Shandong Provincial Hospital Affiliated to Shandong University Jinan ChinaTumor Research and Therapy Center Shandong Provincial Hospital Affiliated to Shandong University Jinan ChinaAbstract Background Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods To identify prognostic biomarkers, we performed targeted next‐generation sequencing of 416 cancer‐related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) was analyzed. Results TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08‐0.77, P = .015) and progression‐free survival (PFS) (HR, 0.35; 95%CI, 0.13‐0.93, P = .030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26‐13.14, P = .019) and OS (HR, 2.78; 95%CI, 0.95‐8.17, P = .062). In a subgroup analysis, while sex and M‐stage were controlled, a much stronger negative effect of YAP1 amplification vs wild‐type in LRFS was observed (log‐rank P = .0067). Conclusion The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored.https://doi.org/10.1002/cam4.2761chemoradiation therapyesophageal squamous cell carcinomalocal recurrence‐free survivalnext‐generation sequencingYAP1 amplification |
| spellingShingle | Honghai Dai Yang W. Shao Xiaoling Tong Xue Wu Jiaohui Pang Alei Feng Zhe Yang YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma Cancer Medicine chemoradiation therapy esophageal squamous cell carcinoma local recurrence‐free survival next‐generation sequencing YAP1 amplification |
| title | YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| title_full | YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| title_fullStr | YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| title_full_unstemmed | YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| title_short | YAP1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| title_sort | yap1 amplification as a prognostic factor of definitive chemoradiotherapy in nonsurgical esophageal squamous cell carcinoma |
| topic | chemoradiation therapy esophageal squamous cell carcinoma local recurrence‐free survival next‐generation sequencing YAP1 amplification |
| url | https://doi.org/10.1002/cam4.2761 |
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