PO.CL01.04 · 临床研究
肺鳞状细胞癌中共享突变的比例提供了可指导治疗方法的洞见
A proportion of shared mutations in lung squamous cell carcinoma provides insights that may guide therapeutic approaches
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肺鳞状细胞癌(LUSC)常在遗传学改变的上皮内发生，然而癌化区域(cancerized field)的临床意义仍不明确。为探究其生物学和预后意义，我们对76例LUSC患者的癌前病变、原发肿瘤组织及其匹配的正常组织进行了全外显子和转录组分析。我们定义了癌前病变与相应肿瘤样本之间共享突变的比例(PSM)，其与较差的无复发生存和总生存呈负相关。有趣的是，高PSM与早期染色体不稳定性、烟草相关的突变特征以及代谢和增殖基因(如RRM2和TIMMDC1)的上调相关。此外，RRM2和TIMMDC1的分子特征在独立的非复发组中富集。另外，PSM低组与PSM高组之间的拷贝数变异和基因表达模式存在显著差异，提示癌化区域内存在克隆演化。这些结果表明，PSM可作为一种新的预后生物标志物，并揭示了LUSC进展中的关键早期事件。
本研究得到韩国国家研究基金会(NRF)资助(RS-2022-NR-071926和RS-2018-NR031072)。
查看英文原文 English abstract
Lung squamous cell carcinoma (LUSC) frequently arises within a genetically altered epithelium, yet the clinical significance of the cancerized field remains unclear.To investigate its biological and prognostic significance, we performed whole-exome and transcriptome analyses on precancer, primary tumor tissues, and their matched normal tissues from 76 LUSC patients. We defined the proportion of shared mutations (PSM) between precancer and corresponding tumor samples, which negatively correlates with poor recurrence-free survival and overall survival. Interestingly, high PSM was associated with early chromosomal instability, tobacco-related mutational signatures, and upregulation of metabolic and proliferative genes such as RRM2 and TIMMDC1 . Furthermore, molecular features of RRM2 and TIMMDC1 were enriched in the independent non-recurrence group. Additionally, copy number variations and gene expression patterns differed significantly between the PSM-low and PSM-high groups, suggesting the presence of clonal evolution within a cancerized field. These results demonstrate that PSM serves as a novel biomarker for prognosis and reveals key early events in the progression of LUSC.
This study was supported by a grant (RS-2022-NR-071926 and RS-2018-NR031072) from the National Research Foundation of Korea (NRF).
利益披露 Disclosure
J. Lee, None..
J. Lim, None..
L. Kim, None..
W. Ryu, None..
S. Park, None..
Y. Choi, None..
S. Lee, None.