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TIMEAS, a promising method for the stratification of testicular germ cell tumor patients with distinct immune microenvironment, clinical outcome and sensitivity to frontline therapies
Jialin Meng1; Jingjing Gao1; Xiao Li1; Rui Gao1; Xiaofan Lu2; Jun Zhou1; Fangrong Yan2; Haitao Wang3,4; Yi Liu1; Zongyao Hao1; Xiansheng Zhang1; Chaozhao Liang1
2023-02-24
Source PublicationCellular Oncology
ISSN2211-3428
Volume46Issue:3Pages:745-759
Abstract

Purpose: With the heterogeneous genetic background, prognosis prediction and therapeutic targets for testicular germ cell tumors (TGCTs) are still unclear. We defined the tumor immune microenvironment activation status (TIMEAS). Methods: We collected a total of 314 TGCT patients from four cohorts, including a 48-case microarray. A nonnegative matrix factorization algorithm was applied to identify the “immune factor”, derived the top 150 weighted genes to divide patients into immune and non-immune classes, and further separated the immune class into activated and exhausted subgroups by nearest template prediction. Tumor mutant burden, gene mutation, and copy number alteration were compared with our recently developed package “MOVICS”. A random forest algorithm was performed to establish a prediction model with fewer genes. Immunohistochemistry staining was performed to identify TIMEAS in the microarray. Results: We constructed the TIMEAS in the TCGA-TGCT cohort and further validated it in the GSE3218 and GSE99420 cohorts. The immune class contained the activated status of T-lymphocytes, B-lymphocytes, and macrophages, while Treg cells and the WNT/TGFβ signature were more activated in the immune-suppressed subgroup. Patients in the immune-exhausted subgroup had the worst prognosis, and 22.9% of patients in the immune-activated subgroup had KRAS mutations, which might stimulate the response of the immune system and lead to a favorable prognosis. The immune-exhausted group benefited more from chemotherapy, while the immune-activated subgroup responded well to anti-PD-1/PD-L1 therapy. FSCN1 was validated as the target of the immune-exhausted microenvironment by immunohistochemistry. Conclusion: TIMEAS classification can separate TGCT patients; patients in the immune-activated subgroup could benefit more from anti-PD-L1 immunotherapy, and those in the immune-exhausted subgroup are more suitable for chemotherapy.

KeywordFscn1 Immune-exhausted Molecular Subtype Testicular Germ Cell Tumor
DOI10.1007/s13402-023-00781-1
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology ; Cell Biology ; Pathology
WOS SubjectOncology ; Cell Biology ; Pathology
WOS IDWOS:000937191300001
PublisherSPRINGERVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
Scopus ID2-s2.0-85148632176
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Citation statistics
Document TypeJournal article
CollectionFaculty of Health Sciences
Cancer Centre
Centre for Precision Medicine Research and Training
Corresponding AuthorXiansheng Zhang; Chaozhao Liang
Affiliation1.Department of Urology, The First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, 218th Jixi Road, 230022, China
2.State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
3.Cancer Center, Faculty of Health Sciences, Center for Precision Medicine Research and Training, University of Macau, SAR, Macao
4.Center for Cancer Research, Clinical Research/NCI/NIH, Bethesda, 20892, United States
Recommended Citation
GB/T 7714
Jialin Meng,Jingjing Gao,Xiao Li,et al. TIMEAS, a promising method for the stratification of testicular germ cell tumor patients with distinct immune microenvironment, clinical outcome and sensitivity to frontline therapies[J]. Cellular Oncology, 2023, 46(3), 745-759.
APA Jialin Meng., Jingjing Gao., Xiao Li., Rui Gao., Xiaofan Lu., Jun Zhou., Fangrong Yan., Haitao Wang., Yi Liu., Zongyao Hao., Xiansheng Zhang., & Chaozhao Liang (2023). TIMEAS, a promising method for the stratification of testicular germ cell tumor patients with distinct immune microenvironment, clinical outcome and sensitivity to frontline therapies. Cellular Oncology, 46(3), 745-759.
MLA Jialin Meng,et al."TIMEAS, a promising method for the stratification of testicular germ cell tumor patients with distinct immune microenvironment, clinical outcome and sensitivity to frontline therapies".Cellular Oncology 46.3(2023):745-759.
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