Genomic Characteristics and the Potential Clinical Implications in Oligometastatic Non-Small Cell Lung Cancer

作者全名："Liao, Rongxin; Chen, Kehong; Li, Jinjin; He, Hengqiu; Yi, Guangming; Huang, Mingfeng; Chen, Rongrong; Shen, Lu; Zhang, Xiaoyue; Xu, Zaicheng; Yang, Zhenzhou; Peng, Yuan"

作者地址："[Liao, Rongxin; Chen, Kehong; Li, Jinjin; He, Hengqiu; Yi, Guangming; Zhang, Xiaoyue; Xu, Zaicheng; Yang, Zhenzhou; Peng, Yuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing, Peoples R China; [Huang, Mingfeng; Chen, Rongrong; Shen, Lu] Geneplus Beijing, Beijing, Peoples R China; [Yang, Zhenzhou] Chongqing Clin Res Ctr Geriatr & Gerontol, Chongqing, Peoples R China; [Yang, Zhenzhou; Peng, Yuan] Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing 400010, Peoples R China"

通信作者："Yang, ZZ; Peng, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing, Peoples R China.; Yang, ZZ; Peng, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Canc Ctr, Chongqing 400010, Peoples R China."

来源：CANCER RESEARCH AND TREATMENT

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001040944900009

JCR分区：Q2

影响因子：4.1

年份：2023

卷号：55

期号：3

开始页：814

结束页：831

文献类型：Article

关键词：Non-small cell lung cancer; Oligometastatic; Genomic profiling; High-throughput nucleotide sequencing; Tumor muta-tional burden

摘要："Purpose Oligometastatic non-small cell lung cancer (NSCLC) patients have been increasingly regarded as a distinct group that could benefit from local treatment to achieve a better clinical outcome. However, current definitions of oligometastasis are solely numerical, which are imprecise because of ignoring the biological heterogeneity caused by genomic characteristics. Our study aimed to profile the molecular alterations of oligometastatic NSCLC and elucidate its potential difference from polymetastasis.Materials and Methods We performed next-generation sequencing to analyze tumors and paired peripheral blood from 77 oligometastatic and 21 polymetastatic NSCLC patients to reveal their genomic characteristics and assess the genetic heterogeneity.Results We found ERBB2, ALK, MLL4, PIK3CB, and TOP2A were mutated at a significantly lower frequency in oligometastasis compared with polymetastasis. EGFR and KEAP1 alterations were mutually exclusive in oligometastatic group. More importantly, oligometastasis has a unique significant enrichment of apoptosis signaling pathway. In contrast to polymetastasis, a highly enriched COSMIC signature 4 and a special mutational process, COSMIC signature 14, were observed in the oligometastatic cohort. According to OncoKB database, 74.03% of oligometastatic NSCLC patients harbored at least one actionable alteration. The median tumor mutation burden of oligometastasis was 5.00 mutations/Mb, which was significantly associated with smoking, DNA damage repair genes, TP53 mutation, SMARCA4 mutation, LRP1B mutation, ABL1 mutation. Conclusion Our results shall help redefine oligometastasis beyond simple lesion enumeration that will ultimately improve the selection of patients with real oligometastatic state and optimize personalized cancer therapy for oligometastatic NSCLC."

基金机构：Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0208]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [KRYC-YQ-2116]; Project of Chongqing Technology Innovation and Application Development [CSTC2021jscx-gksb-N0022]; Chongqing Talents Program [CQYC20200303151]

基金资助正文："This work was supported by grants from the Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0208) , Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (No. KRYC-YQ-2116) to Yuan Peng and the Project of Chongqing Technology Innovation and Application Development (No. CSTC2021jscx-gksb-N0022) and Chongqing Talents Program (No. CQYC20200303151) to Zhenzhou Yang."