2. Academic Validation
  3. HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments

HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments

  • J Transl Med. 2024 Apr 27;22(1):391. doi: 10.1186/s12967-024-05218-3.
Jianrong Bai # 1 2,  Yangyang Zhao # 3 4,  Kaijia Shi # 3,  Yonghao Fan 3,  Yanping Ha 1,  Yan Chen 3,  Botao Luo 1,  Yanda Lu 5,  Wei Jie 6 7 8,  Zhihua Shen 9
Affiliations

Affiliations

  • 1 Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China.
  • 2 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China.
  • 3 Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China.
  • 4 Emergency and Trauma College, Hainan Medical University, Haikou, 571199, China.
  • 5 Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China. hy0203141@hainmc.edu.cn.
  • 6 Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China. wei_jie@hainmc.edu.cn.
  • 7 Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China. wei_jie@hainmc.edu.cn.
  • 8 Emergency and Trauma College, Hainan Medical University, Haikou, 571199, China. wei_jie@hainmc.edu.cn.
  • 9 Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China. shenzh@gdmu.edu.cn.
  • # Contributed equally.
PMID: 38678297 DOI: 10.1186/s12967-024-05218-3
Abstract

Background: Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited.

Methods: We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored.

Results: LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion.

Conclusions: High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

Keywords

Gliomas; HIF-1α; LAMC1; Pan-cancer; Prognosis.

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