ESCO2's oncogenic role in human tumors: a pan-cancer analysis and experimental validation

Our plain-English summary of ESCO2's oncogenic role in human tumors: a pan-cancer analysis and experimental validation, by Y. Huang, D. Chen, Y. Bai, et al (BMC Cancer, 2024).

The study

• Authors: Y. Huang, D. Chen, Y. Bai, Y. Zhang, Z. Zheng, Q. Fu, B. Yi, Y. Jiang, Z. Zhang, J. Zhu
• Journal: BMC Cancer
• Published: 2024;24(1):452
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function.

Methods: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro.

Results: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration.

Conclusions: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

© 2024. The Author(s).

In plain English

This laboratory and computer-based study looked at a gene called ESCO2 across many cancer types. It did not study asbestos. Mesothelioma data came only from a public database, as one of 33 cancer types, and was not used in the laboratory experiments. The authors analysed public gene databases, mainly The Cancer Genome Atlas (11,315 samples) and the Genotype-Tissue Expression Project. They also tested three pairs of kidney and bladder tumor and nearby tissue samples, and kidney (A498) and bladder (T24) cancer cell lines. ESCO2 expression was considerably higher in tumor tissue in 30 of 33 cancer types and significantly lower in acute myeloid leukemia. In nine cancer types, including mesothelioma, patients whose tumors had high ESCO2 survived for shorter periods. In thymoma and colon and rectal cancers, high ESCO2 was linked to better outcomes. Turning ESCO2 down in the cell lines reduced cell growth, invasion and migration. The authors concluded that ESCO2 is a potential biomarker and cancer-promoting gene. They noted that they had no clinical cohorts of their own for judging ESCO2's diagnostic and prognostic value, and did no animal experiments.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pan-cancer bioinformatics analysis of public gene-expression databases, with laboratory (in vitro) cell-line experiments and a small set of patient tissue samples
• Who was studied: Public database tumor and normal samples: TCGA, with 11,315 samples across 33 cancer types, combined with GTEx. Also three pairs of kidney renal clear cell carcinoma (KIRC) and bladder urothelial carcinoma (BLCA) tissue samples with adjacent tissue from the Second Hospital of Tianjin Medical University, China, and the A498 (clear cell renal cell carcinoma) and T24 (bladder cancer) cell lines. Mesothelioma (MESO) was one of the database cancer types; its subtype was not specified. It was included in the survival analyses and in the 12-cancer gene set enrichment analysis, but not in the laboratory experiments.
• Exposure: No asbestos or fiber exposure was studied. The factor studied was the level of ESCO2 gene expression. Patients were split into high and low ESCO2 groups (by median value, or by a best cutoff point for survival analyses), and ESCO2 was reduced in cell lines using siRNA.
• Main results:
  • Combining TCGA and GTEx data, ESCO2 expression was considerably higher in tumor tissue in 30 of 33 cancer types. Acute myeloid leukemia (LAML) showed significantly lower levels.
  • In Kaplan-Meier survival analyses, patients with high ESCO2 expression had short survival periods in ACC, KICH, KIRC, KIRP, LGG, LIHC, LUAD, mesothelioma (MESO) and PAAD. No survival figures were given in the text.
  • In thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 expression was linked to better outcomes.
  • Tumor size was positively linked with ESCO2 expression in LIHC, KIRC, KIRP and LUAD.
  • In the kidney (KIRC) and bladder (BLCA) tissue samples, ESCO2 protein levels were noticeably higher in tumor than in nearby tissue.
  • Reducing ESCO2 in A498 kidney cancer cells significantly decreased their ability to proliferate. The same was found in T24 bladder cancer cells. ESCO2 silencing also reduced invasion and migration.
  • After ESCO2 was reduced, expression of the gene CDK1 was significantly decreased. The authors identified CDK1 as a downstream gene.
• The authors' conclusion: The authors concluded that ESCO2 is a potential pan-cancer biomarker and oncogene that can predict prognosis in the listed cancers, including mesothelioma. They also concluded that it is involved in cell division and is a potential therapeutic target.
• Limitations the authors state:
  • The authors did not use any clinical cohorts of their own to evaluate ESCO2's diagnostic and prognostic value; they relied on public database data.
  • The upstream and downstream pathways of ESCO2 were not fully examined, and its precise molecular mechanism remains unknown.
  • No experiments were done in living animals (in vivo).

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer.

Medical terms in this study, explained in our Lexicon: Prognosis, Carcinogenesis, Carcinoma, Lung Adenocarcinoma, Mesothelioma, Adenocarcinoma, Biomarker.

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