Identification of SURF4 and RALGAPA1 as promising therapeutic targets in glioblastoma and pan-cancer through integrative multi-omics, CRISPR-Cas9 screening and prognostic meta-analysis

被引：0

作者：

Fei Wang ^{[1
]}

Yuxuan Chen ^{[2
]}

Run Huang ^{[2
]}

Dengfeng Lu ^{[1
]}

Juyi Zhang ^{[1
]}

Yanbo Yang ^{[3
]}

Hanhan Dang ^{[4
]}

Meirong Liu ^{[5
]}

Zhouqing Chen ^{[1
]}

Xiaoou Sun ^{[1
]}

Zhong Wang ^{[1
]}

机构：

[1] The First Affiliated Hospital of Soochow University,Department of Neurosurgery

[2] Suzhou Medical College of Soochow University,Department of Oncology, Division of Pediatric Oncology

[3] Johns Hopkins School of Medicine,Department of Neurology

[4] China-Japan Friendship Hospital,undefined

[5] Chinese Academy of Medical Sciences & Peking Union Medical College,undefined

[6] The First Affiliated Hospital of Soochow University,undefined

来源：

Cancer Immunology, Immunotherapy | / 74卷 / 6期

关键词：

SURF4; RALGAPA1; Glioblastoma; Multi-omics; Pan-cancer;

D O I：

10.1007/s00262-025-04034-y

中图分类号：

学科分类号：

摘要：

Glioblastoma (GBM) is the most aggressive and malignant type of primary brain tumor, with a median survival time of less than two years and a uniformly poor prognosis, despite multimodal therapeutic approaches, which highlights an urgent need for novel therapeutic targets. In this study, by integrative multi-omics analysis from CPTAC database, DepMap database and seven independent GBM cohorts, four hub genes (CD44, SURF4, IGSF3 and RALGAPA1) were identified as essential genes regulated by cancer driver genes with robust prognostic value. GBM multi-omics data from public and in-house cohorts validated that CD44 and SURF4 might be synthetic lethal partners of loss-of-function tumor suppressor genes. Analysis for immune-related pathway activity revealed complex regulation relationships of the four hub genes in tumor microenvironment (TME). Further investigation on SURF4 in pathway activity, immune therapy response and drug sensitivity proposed that SURF4 emerged as a promising therapeutic target for GBM, even for pan-cancer. Pan-cancer multi-omics exploration suggested that RALGAPA1 may be a tumor suppressor gene. By screening the first-generation and second-generation DepMap database, four genes (CCDC106, GAL3ST1, GDI2 and HSF1) might be considered as synthetic targets after mutation of RALGAPA1 as a tumor suppressor gene.

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