التفاصيل البيبلوغرافية
| العنوان: |
Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages. |
| المؤلفون: |
Ho, Hao1 (AUTHOR), Yu, Sung-Liang1,2,3,4,5,6,7 (AUTHOR), Chen, Hsuan-Yu1 (AUTHOR), Yuan, Shin-Sheng1 (AUTHOR), Su, Kang-Yi2,3,4 (AUTHOR), Hsu, Yi-Chiung8 (AUTHOR), Hsu, Chung-Ping9 (AUTHOR), Chuang, Cheng-Yen9 (AUTHOR), Chang, Ya-Hsuan1 (AUTHOR), Li, Yu-Cheng1 (AUTHOR), Cheng, Chiou-Ling2 (AUTHOR), Chang, Gee-Chen1,10,11,12,13,14 (AUTHOR) cshy1888@csh.org.tw, Yang, Pan-Chyr1,3,15,16 (AUTHOR) pcyang@ntu.edu.tw, Li, Ker-Chau1,17 (AUTHOR) kcli@stat.sinica.edu.tw |
| المصدر: |
Lung Cancer (01695002). Oct2023, Vol. 184, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*SOMATIC mutation, *GENE expression, *MICRORNA, *TUMOR classification, *LUNGS |
| مستخلص: |
• WES of a Taiwan stage I LUAD cohort identified 16 mutations associated with poor RFS. • These 16 mutations were harbored at EGFR , KRAS , TP53 , CTNNB1 and six other genes. • An index, maxVAF, summarized the overall mutation load from genes other than EGFR. • Higher relapse risk was found for stage I patients with high maxVAF or high miR-31. • At stage IB, miR-182 , -183 , and -196a correlated with EGFR mutation and poor RFS. About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. We found sixteen nonsynonymous mutations harbored at EGFR , KRAS , TP53 , CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22–26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31 ; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182 , miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
