Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer
Open accessAbstract
BACKGROUND: A better understanding of the development of metastatic disease and the identification of molecular markers for cancer spread would be useful for the design of improved treatment strategies. This study was conducted to identify gene expressions associated with metastatic phenotypes of locally advanced cervical carcinomas and investigate whether gains or losses of these genes could play a role in regulation of the transcripts. Gene expressions and copy number changes were determined in primary tumors from 29 patients with and 19 without diagnosed lymph node metastases by use of cDNA and genomic microarray techniques, respectively. RESULTS: Thirty-one genes that differed in expression between the node positive and negative tumors were identified. Expressions of eight of these genes (MRPL11, CKS2, PDK2, MRPS23, MSN, TBX3, KLF3, LSM3) correlated with progression free survival in univariate analysis and were therefore more strongly associated with metastatic phenotypes than the others. Immunohistochemistry data of CKS2 and MSN showed similar relationships to survival. The prognostic genes clustered into two groups, suggesting two major metastatic phenotypes. One group was associated with rapid proliferation, oxidative phosphorylation, invasiveness, and tumor size (MRPS23, MRPL11, CKS2, LSM3, TBX3, MSN) and another with hypoxia tolerance, anaerobic metabolism, and high lactate content (PDK2, KLF3). Multivariate analysis identified tumor volume and PDK2 expression as independent prognostic variables. Gene copy number changes of the differentially expressed genes were not frequent, but correlated with the expression level for seven genes, including MRPS23, MSN, and LSM3. CONCLUSION: Gene expressions associated with known metastatic phenotypes of cervical cancers were identified. Our findings may indicate molecular mechanisms underlying development of these phenotypes and be useful as markers of cancer spread. Gains or losses of the genes may be involved in development of the metastatic phenotypes in some cases, but other mechanisms for transcriptional regulation are probably important in the majority of tumors.
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Tbx3 is involved in the carcinogenesis of multiple types of human cancers.
“As Tbx3 is involved in the carcinogenesis of multiple types of human cancers, our findings suggest an important target for anti-cancer drug development.”
From Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma (2018) · cites this paper as [31]
The Discussion (page not specified) identifies TBX3 as a prognostic gene in cervical cancer and says it probably plays a role in tumor growth and may participate in cell-cycle control. It does not establish TBX3 involvement in carcinogenesis across multiple types of human cancer; its mentions of other cancers concern different genes. (LLM, conf=0.86)
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“Interestingly, TBX3 is methylated in metastatic cervical cancer, DU-145 prostate cancer cells, bladder cancer, urothelial carcinoma, in the AGS gastric cancer cell line, glioblastoma and glioblastoma stem cells, and the methylation of TBX3 was associated with a poor overall survival, resistance to cancer therapy and a…”
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- Authors
- Lyng, H., Brøvig, R. S., Svendsrud, D. H., Holm, R., Kaalhus, O., Knutstad, K., Oksefjell, H., Sundfør, K., Kristensen, G. B., & Stokke, T.
- Affiliations
- University of Oslo (NO)
- Corresponding author
- Lyng, Heidi
- Venue
- BMC Genomics
- Published
- 2006-10-20
- Volume
- 7
- Issue
- 1
- Pages
- 268-268
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC1626467
- OpenAlex
- W2170540646
- Cited by
- 158
- References
- 56
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 13 · 2017: 12 · 2016: 3 · 2015: 11 · 2014: 8 · 2013: 10 · 2012: 11
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Genomics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Norges Forskningsråd
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- cervical cancer, lymph node metastasis, metastatic phenotype, gene expression, copy number alterations, prognostic genes, PDK2, MSN, CKS2, TBX3, KLF3, progression-free survival, tumor volume, hypoxia tolerance, oxidative phosphorylation, anaerobic metabolism, metastasis markers
- MeSH terms
- Analysis of Variance, Carcinoma, Squamous Cell, Carrier Proteins, Uterine Cervical Neoplasms, Female, Humans, Immunohistochemistry, Lymphatic Metastasis, Microfilament Proteins, Phenotype, Protein Kinases, Regression Analysis, Ribosomal Proteins, Gene Expression Regulation, Neoplastic, Cluster Analysis, Proportional Hazards Models, Survival Analysis, Protein Serine-Threonine Kinases, Gene Dosage, Cell Cycle Proteins, Oligonucleotide Array Sequence Analysis, T-Box Domain Proteins, Gene Expression Profiling, CDC2-CDC28 Kinases, Kruppel-Like Transcription Factors, 3-Phosphoinositide-Dependent Protein Kinases
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