2. Academic Validation
  3. High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML

High FAAP24 expression reveals poor prognosis and an immunosuppressive microenvironment shaping in AML

  • Cancer Cell Int. 2023 Jun 17;23(1):117. doi: 10.1186/s12935-023-02937-3.
Xiebing Bao # 1 2,  Jingyun Chi # 3,  Yiwei Zhu # 4,  Minfeng Yang 5,  Jiahui Du 3,  Zaixiang Tang 6,  Xiaogang Xu 7,  Genxiang Mao 7,  Zhibing Wu 8,  Jun Chen 7,  Jingsheng Hua 9,  Ting Xu 10 11,  Song-Bai Liu 12
Affiliations

Affiliations

  • 1 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
  • 2 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China.
  • 3 Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, 28 Kehua Road, Suzhou, 215009, China.
  • 4 Suzhou Medical College, Soochow University, Suzhou, 215006, China.
  • 5 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, P.R. China.
  • 6 Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, 215123, China.
  • 7 Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang Province, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, China.
  • 8 Department of Oncology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, China.
  • 9 Department of Hematology, Taizhou Municipal Hospital Affiliated to Taizhou University, Taizhou, 318000, China. huajingsheng@sohu.com.
  • 10 National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China. xuting83_xuye@163.com.
  • 11 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215006, China. xuting83_xuye@163.com.
  • 12 Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, 28 Kehua Road, Suzhou, 215009, China. liusongbai@126.com.
  • # Contributed equally.
PMID: 37328842 DOI: 10.1186/s12935-023-02937-3
Abstract

Background: As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort.

Methods: In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro.

Results: Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and Cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML.

Conclusions: In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation.

Keywords

AML; Chelerythrine; FAAP24; Immunosuppression; Prognosis.

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