Clinicopathological and prognostic significance of HIF-1α and HIF-2α expression in small cell lung cancer
Abstract
Previous work from our laboratory has demonstrated that urokinase plasminogen activator receptor (uPAR) may be a potential stem-like cell marker in SCLC. Hypoxia inducible factor (HIF) has been shown to transcriptionally regulate uPAR expression. Therefore, the aim of this study was to evaluate the relationship between HIF-1α/HIF-2α and uPAR expression, and to investigate the role of HIF-1α/HIF-2α in the clinical pathology and prognosis of patients with SCLC. Immunohistochemical analysis showed that HIF-1α/HIF-2α staining was mainly present in the nuclei of cancer cells. HIF-1α-positive cells were diffusely distributed in the nests of the tumor, while HIF-2α-positive cells were frequently distributed around necrotic regions. HIF-1α and HIF-2α were expressed in 22/45 (48.9%) and in 11/45 (24.4%) of SCLC patients, respectively; HIF-1α did not correlate with any of the clinicopathological parameters as evaluated in our study. In contrast, a significant association of HIF-2α with uPAR expression, tumor growth and distant metastasis (p=0.001, 0.010 and 0.008, respectively) was noted; Kaplan-Meier survival analysis demonstrated that HIF-1α and HIF-2α expressions were related to shortened overall survival (p=0.027 and 0.001, respectively). However, in multivariate analysis, only HIF-2α expression and distant metastasis were the independent prognostic indicators of SCLC (p=0.004 and 0.018, respectively). Our results suggest that HIF-2α may represent a more aggressive phenotype in SCLC. HIF-2α, in addition to HIF-1α, needs to be considered when developing drugs that target HIF pathway.
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HIF-2 expression in primary tumors is associated with distant metastasis in patients with small cell lung and breast cancers.
“HIF-2 expression in primary tumors is also associated with distant metastasis in patients with small cell lung and breast cancers”
From Hypoxic control of metastasis (2016) · cites this paper as [39]
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- Authors
- Luan, Y., Gao, C., Miao, Y., Li, Y., Wang, Z., & Qiu, X.
- Affiliations
- Tianjin Medical University (CN)
- Corresponding author
- Qiu, Xiaofei
- Venue
- Pathology - Research and Practice
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 209
- Issue
- 3
- Pages
- 184-189
- ISSN
- 0344-0338 (ISSN-L)
- OpenAlex
- W2039982867
- Cited by
- 31
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 3
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pathology - Research and Practice (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- small cell lung cancer, hypoxia-inducible factor-1α, HIF-2α, urokinase-type plasminogen activator receptor, prognostic factors, distant metastasis, overall survival, tumor aggressiveness, HIF pathway, stem-like cells
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Adult, Aged, Female, Humans, Immunohistochemistry, Lung Neoplasms, Male, Middle Aged, Prognosis, Biomarkers, Tumor, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Kaplan-Meier Estimate, Small Cell Lung Carcinoma
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