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Background <p>The orchestration of mitotic checkpoint execution depends on the enzymatic activity of the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase. APC/C functions with the assistance of the adapter protein Cdc20 and the E2 ubiquitin-conjugating enzyme UbcH10 for orderly progression of mitosis. Reportedly, deregulated expression of either <i>CDC20</i> or <i>UBCH10</i> is associated with increased tumor aggressiveness in various human malignancies, including head and neck squamous cell carcinoma (HNSC). Previously, our laboratory reported that Cdc20 transcriptionally activates <i>UBCH10</i> expression in cultured HNSC cells. This led us to investigate their correlated expression in primary HNSC malignancies in a prospective Eastern Indian study cohort and The Cancer Genome Atlas (TCGA) dataset.</p> Methods <p>Quantitative PCR and immunohistochemistry analyses were performed to assess <i>CDC20</i> and <i>UBCH10</i> expression in primary HNSC patient samples of a prospective Eastern-Indian cohort. The RNA-sequencing data were retrieved from TCGA-head and neck squamous cell carcinoma (HNSC) cohort. Additionally, FISH assay was carried out to investigate cellular ploidy status in HNSC tumor and adjacent normal samples, as well as in cultured HNSC cells and validated in silico in TCGA cohorts. Assays to evaluate proliferation, migration and invasion of HNSC cells were conducted under the influence of correlated expression of <i>CDC20</i> and <i>UBCH10</i>. Kaplan–Meier analyses was performed to determine the impact of survival outcome under the influence of correlated <i>CDC20-UBCH10</i> expression.</p> Results <p>The initial results revealed correlated overexpression of both genes in a significant number of primary HNSC samples from the prospective cohort. Concordantly, gene expression data from the TCGA-HNSC cohort revealed a similar correlation. In addition, HNSC-affected individuals with this correlated overexpression showed an increased level of cellular aneuploidy. More importantly, Kaplan‒Meier analyses revealed that patients harboring this correlated expression signature had the poorest survival outcome. Findings of exacerbation in proliferation, migration and invasion properties of cultured HNSC cells, under the influence of concerted overexpression of <i>CDC20</i>-<i>UBCH10</i>, further corroborated our findings. Further investigations revealed that this expression signature occurs in several other malignancies of solid tissues and negatively influences their survival outcomes.</p> Conclusions <p>Together, these findings delineate the correlation of <i>CDC20</i>-<i>UBCH10</i> overexpression with survival outcomes in patients with primary HNSC and other solid tumors and suggest the potential of this expression signature for prognostication.</p>

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A signature of correlated CDC20 and UBCH10 expression indicates poor prognosis in primary head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Ratnadip Paul,
  • Sayani Sinharay,
  • Debanil Dhar,
  • Purandar Sarkar,
  • Puja Chakraborty,
  • Saradindu Ghosh,
  • Anup Roy,
  • Abhik Saha,
  • Susanta Roychoudhury,
  • Somsubhra Nath

摘要

Background

The orchestration of mitotic checkpoint execution depends on the enzymatic activity of the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase. APC/C functions with the assistance of the adapter protein Cdc20 and the E2 ubiquitin-conjugating enzyme UbcH10 for orderly progression of mitosis. Reportedly, deregulated expression of either CDC20 or UBCH10 is associated with increased tumor aggressiveness in various human malignancies, including head and neck squamous cell carcinoma (HNSC). Previously, our laboratory reported that Cdc20 transcriptionally activates UBCH10 expression in cultured HNSC cells. This led us to investigate their correlated expression in primary HNSC malignancies in a prospective Eastern Indian study cohort and The Cancer Genome Atlas (TCGA) dataset.

Methods

Quantitative PCR and immunohistochemistry analyses were performed to assess CDC20 and UBCH10 expression in primary HNSC patient samples of a prospective Eastern-Indian cohort. The RNA-sequencing data were retrieved from TCGA-head and neck squamous cell carcinoma (HNSC) cohort. Additionally, FISH assay was carried out to investigate cellular ploidy status in HNSC tumor and adjacent normal samples, as well as in cultured HNSC cells and validated in silico in TCGA cohorts. Assays to evaluate proliferation, migration and invasion of HNSC cells were conducted under the influence of correlated expression of CDC20 and UBCH10. Kaplan–Meier analyses was performed to determine the impact of survival outcome under the influence of correlated CDC20-UBCH10 expression.

Results

The initial results revealed correlated overexpression of both genes in a significant number of primary HNSC samples from the prospective cohort. Concordantly, gene expression data from the TCGA-HNSC cohort revealed a similar correlation. In addition, HNSC-affected individuals with this correlated overexpression showed an increased level of cellular aneuploidy. More importantly, Kaplan‒Meier analyses revealed that patients harboring this correlated expression signature had the poorest survival outcome. Findings of exacerbation in proliferation, migration and invasion properties of cultured HNSC cells, under the influence of concerted overexpression of CDC20-UBCH10, further corroborated our findings. Further investigations revealed that this expression signature occurs in several other malignancies of solid tissues and negatively influences their survival outcomes.

Conclusions

Together, these findings delineate the correlation of CDC20-UBCH10 overexpression with survival outcomes in patients with primary HNSC and other solid tumors and suggest the potential of this expression signature for prognostication.