Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Research

RACGAP1 promotes the progression and poor prognosis of lung adenocarcinoma through its effects on the cell cycle and tumor stemness

Authors: Yafeng Liu, Tao Han, Rui Miao, Jiawei Zhou, Jianqiang Guo, Zhi Xu, Yingru Xing, Ying Bai, Jing Wu, Dong Hu

Published in: BMC Cancer | Issue 1/2024

Login to get access

Abstract

Objection

Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma.

Methods

First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models.

Results

First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells.

Conclusion

RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.
Appendix
Available only for authorised users
Literature
1.
2.
Catalano V, et al. Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol. 2013;23(6 Pt B):522–32.
3.
4.
Yu J, et al. Mechanistic exploration of Cancer Stem cell marker voltage-dependent Calcium Channel alpha2delta1 subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer. Clin Cancer Res. 2018;24(9):2148–58.CrossRefPubMed
5.
Kuo MH, et al. Cross-talk between SOX2 and TGFbeta Signaling regulates EGFR-TKI Tolerance and Lung Cancer Dissemination. Cancer Res. 2020;80(20):4426–38.CrossRefPubMed
6.
7.
Gettinger SN, et al. Nivolumab Plus Ipilimumab vs Nivolumab for previously treated patients with stage IV squamous cell Lung Cancer: the Lung-MAP S1400I phase 3 Randomized Clinical Trial. JAMA Oncol. 2021;7(9):1368–77.CrossRefPubMedPubMedCentral
8.
Herbst RS, et al. Phase 1 expansion cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naive NSCLC. J Thorac Oncol. 2021;16(2):289–98.CrossRefPubMed
9.
Nogami N, et al. IMpower150 final exploratory analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC patient subgroups with EGFR mutations or metastases in the liver or brain. J Thorac Oncol. 2022;17(2):309–23.CrossRefPubMed
10.
Owonikoko TK, et al. Nivolumab and Ipilimumab as maintenance therapy in extensive-disease small-cell Lung Cancer: CheckMate 451. J Clin Oncol. 2021;39(12):1349–59.CrossRefPubMedPubMedCentral
11.
De Stefano L, et al. Tumor necrosis factor-alpha inhibitor-related autoimmune disorders. Autoimmun Rev. 2023;22(7):103332.CrossRefPubMed
12.
13.
14.
15.
Kanehisa M, et al. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.CrossRefPubMed
16.
Li J, Hou W. Expression patterns and clinical significances of PBK in Lung cancer: an analysis based on Oncomine database. Transl Cancer Res. 2021;10(5):2036–43.CrossRefPubMedPubMedCentral
17.
Wang P, et al. UPF1 regulates FOXO1 protein expression by promoting PBK transcription in non-small cell Lung cancer. Biochem Biophys Res Commun. 2023;666:10–20.CrossRefPubMed
18.
Shih MC, et al. TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in Lung cancer. Oncogene. 2012;31(19):2389–400.CrossRefPubMed
19.
Wang MY, et al. Pseudogene RACGAP1P activates RACGAP1/Rho/ERK signalling axis as a competing endogenous RNA to promote hepatocellular carcinoma early recurrence. Cell Death Dis. 2019;10(6):426.CrossRefPubMedPubMedCentral
20.
Pliarchopoulou K, et al. Prognostic significance of RACGAP1 mRNA expression in high-risk early Breast cancer: a study in primary tumors of Breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial. Cancer Chemother Pharmacol. 2013;71(1):245–55.CrossRefPubMed
21.
Zhao W, et al. RACGAP1 is transcriptionally regulated by E2F3, and its depletion leads to mitotic catastrophe in esophageal squamous cell carcinoma. Ann Transl Med. 2020;8(15):950.CrossRefPubMedPubMedCentral
22.
Saigusa S, et al. Clinical significance of RacGAP1 expression at the invasive front of gastric cancer. Gastric Cancer. 2015;18(1):84–92.CrossRefPubMed
23.
Yang XM, et al. Overexpression of rac GTPase activating protein 1 contributes to proliferation of Cancer cells by reducing Hippo Signaling to Promote Cytokinesis. Gastroenterology. 2018;155(4):1233–1249e22.CrossRefPubMed
24.
Wang C, et al. Rac GTPase activating protein 1 promotes oncogenic progression of epithelial Ovarian cancer. Cancer Sci. 2018;109(1):84–93.CrossRefPubMed
25.
Warga RM, et al. Progressive loss of RacGAP1/ogre activity has sequential effects on cytokinesis and zebrafish development. Dev Biol. 2016;418(2):307–22.CrossRefPubMed
26.
Schneid S, et al. The BRCT domains of ECT2 have distinct functions during cytokinesis. Cell Rep. 2021;34(9):108805.CrossRefPubMed
27.
Kim H, et al. Centralspindlin assembly and 2 phosphorylations on MgcRacGAP by Polo-like kinase 1 initiate Ect2 binding in early cytokinesis. Cell Cycle. 2014;13(18):2952–61.CrossRefPubMedPubMedCentral
28.
Zhou D, et al. Long non-coding RNA RACGAP1P promotes Breast cancer invasion and Metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission. Mol Oncol. 2021;15(2):543–59.CrossRefPubMed
29.
30.
31.
32.
Kunihiro AG, et al. CD133 as a biomarker for an autoantibody-to-ImmunoPET paradigm for the early detection of small cell Lung Cancer. J Nucl Med. 2022;63(11):1701–7.PubMedPubMedCentral
33.
34.
Coronado D, et al. A short G1 phase is an intrinsic determinant of naive embryonic stem cell pluripotency. Stem Cell Res. 2013;10(1):118–31.CrossRefPubMed
35.
Wang XQ, et al. CDK1-PDK1-PI3K/Akt signaling pathway regulates embryonic and induced pluripotency. Cell Death Differ. 2017;24(1):38–48.CrossRefPubMed
36.
Neganova I, et al. Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells. Oncogene. 2009;28(1):20–30.CrossRefPubMed
37.
Filipczyk AA, et al. Differentiation is coupled to changes in the cell cycle regulatory apparatus of human embryonic stem cells. Stem Cell Res. 2007;1(1):45–60.CrossRefPubMed
38.
Gonzales KA, et al. Deterministic restriction on pluripotent state dissolution by cell-cycle pathways. Cell. 2015;162(3):564–79.CrossRefPubMed
39.
Zhang WW, et al. Cdk1 is required for the self-renewal of mouse embryonic stem cells. J Cell Biochem. 2011;112(3):942–8.CrossRefPubMed
40.
Neganova I, et al. CDK1 plays an important role in the maintenance of pluripotency and genomic stability in human pluripotent stem cells. Cell Death Dis. 2014;5(11):e1508.CrossRefPubMedPubMedCentral
Metadata
Title
RACGAP1 promotes the progression and poor prognosis of lung adenocarcinoma through its effects on the cell cycle and tumor stemness
Authors
Yafeng Liu
Tao Han
Rui Miao
Jiawei Zhou
Jianqiang Guo
Zhi Xu
Yingru Xing
Ying Bai
Jing Wu
Dong Hu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11761-x

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Research

Is low-dose computed tomography for lung cancer screening conveniently accessible in China? A spatial analysis based on cross-sectional survey

Research

Convolutional neural network-based magnetic resonance image differentiation of filum terminale ependymomas from schwannomas

Research

Upregulation of CENPM promotes breast carcinogenesis by altering immune infiltration

Research

Predictive value of CT and 18F-FDG PET/CT features on spread through air space in lung adenocarcinoma

Research

Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China

Research

The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits