Identification and Validation of RELN Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer

作者全名："Li, Zhenpeng; Wang, Xin; Yang, Yi; Shi, Fuyan; Zhang, Wenjing; Wang, Qinghua; Wang, Suzhen"

作者地址："[Li, Zhenpeng] Weifang Med Univ, Sch Med Lab, Weifang 261053, Peoples R China; [Wang, Xin] Chongqing Med Univ, Affiliated Hosp 2, Chongqing 400000, Peoples R China; [Yang, Yi; Shi, Fuyan; Zhang, Wenjing; Wang, Qinghua; Wang, Suzhen] Weifang Med Univ, Sch Publ Hlth, Dept Hlth Stat, Key Lab Med & Hlth Shandong Prov, Weifang 261053, Peoples R China"

通信作者："Wang, QH; Wang, SZ (通讯作者)，Weifang Med Univ, Sch Publ Hlth, Dept Hlth Stat, Key Lab Med & Hlth Shandong Prov, Weifang 261053, Peoples R China."

来源：CELLS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000897458900001

JCR分区：Q2

影响因子：6

年份：2022

卷号：11

期号：23

开始页：　

结束页：　

文献类型：Article

关键词：RELN mutations; immune checkpoint inhibitor; melanoma; non-small cell lung cancer; molecular determinant

摘要："Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the RELN mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind RELN mutations. Melanoma patients with RELN mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51-0.87, p = 0.003). A higher response rate was also noticed in RELN-mutated patients (38.9% vs. 28.3%, p = 0.017). The association of RELN mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with RELN mutations. In this study, RELN mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level."

基金机构：Medicine and Health Science and Technology Development Plan Project of Shandong Province; National Natural Science Foundation of China [202112050480]; [32200512]; [32000495]

基金资助正文："This research was funded by the Medicine and Health Science and Technology Development Plan Project of Shandong Province (grant number 202112050480), National Natural Science Foundation of China (grant number 32200512 and 32000495), and the APC was funded by National Natural Science Foundation of China (grant number 32200512)."