Comprehensive analysis to identify PUS7 as a prognostic biomarker from pan-cancer analysis to osteosarcoma validation

Our plain-English summary of Comprehensive analysis to identify PUS7 as a prognostic biomarker from pan-cancer analysis to osteosarcoma validation, by B. Dong, B. Wang, M. Fan, et al (Aging, 2024).

The study

• Authors: B. Dong, B. Wang, M. Fan, J. Zhang, Z. Zhao
• Journal: Aging
• Published: 2024;16(10):9188-9203
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Aim: Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine synthases, but the literature on this enzyme is limited to several cancer types. Currently, no investigation has been performed on the systematic pan-cancer analysis concerning PUS7 role in cancer diagnosis and prognosis.

Methods: Employing public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), UALCAN and Tumor Immune Single-cell Hub (TISCH), this work investigated the PUS7 carcinogenesis in pan-cancer. Differential expression analysis, prognostic survival analysis and biological function were systematically performed. Furthermore, PUS7 potential as an osteosarcoma biomarker for diagnosis and prognosis was assessed in this study.

Results: The findings indicated that PUS7 was overexpressed in the majority of malignancies. High PUS7 expression contributed to the poor prognosis among 11 cancer types, including Adrenocortical Cancer (ACC), Bladder Cancer (BLCA), Liver Cancer (LIHC), Kidney Papillary Cell Carcinoma (KIRP), Mesothelioma (MESO), Lower Grade Glioma (LGG), Kidney Chromophobe (KICH), Sarcoma (SARC), osteosarcoma (OS), Pancreatic Cancer (PAAD), and Thyroid Cancer (THCA). In addition, elevated PUS7 expression was linked to advanced TNM across multiple malignancies, including ACC, BLCA, KIRP, LIHC and PAAD. The function enrichment analysis revealed that PUS7 participates in E2F targets, G2M checkpoint, ribosome biogenesis, and rRNA metabolic process. Moreover, PUS7 is also a reliable biomarker and a potential therapeutic target for osteosarcoma.

Conclusions: In summary, PUS7 is a putative pan-cancer biomarker that reliably forecasts cancer patients' prognosis. In addition, this enzyme regulates the cell cycle, ribosome biogenesis, and rRNA metabolism. Most importantly, PUS7 possibly regulates osteosarcoma initiation and progression.

In plain English

This was a laboratory and database study of a gene called PUS7, which makes an enzyme that chemically modifies RNA. The article does not discuss asbestos. Using public genetic databases covering 33 cancer types, the authors compared PUS7 expression levels in tumors and normal tissue and tested whether those levels were linked to patient survival. They also examined osteosarcoma, a bone cancer, using public datasets and tissue from 10 patients treated at a hospital in Tianjin, China. PUS7 was significantly higher in tumor tissue in 25 of 33 cancer types. Higher PUS7 was associated with poorer outcomes in 11 cancer types, one of which was mesothelioma. The text gives no figures for mesothelioma and does not say whether those cases were pleural or peritoneal. In osteosarcoma, PUS7 was higher in tumors than in nearby normal tissue, and higher in patients whose cancer had spread. The authors concluded that PUS7 is a putative pan-cancer biomarker and may control osteosarcoma initiation and progression. They noted that few osteosarcoma datasets were available.

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: Bioinformatics analysis of public gene-expression databases (pan-cancer), with a small immunohistochemistry (tissue staining) check in osteosarcoma samples
• Who was studied: About 10,000 patients across 33 cancer types in public databases (TCGA, with GTEx normal tissue), plus public osteosarcoma datasets. Also 10 pairs of osteosarcoma and adjacent tissue samples from patients aged 8 to 16 at Tianjin Hospital of Tianjin University, China, admitted 2020 to 2022.
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the expression level of the PUS7 gene, with patients split into high- and low-PUS7 groups.
• Main results:
  • Combining TCGA and GTEx samples, PUS7 levels were significantly higher in tumor tissue in 25 of 33 cancer types. The exceptions were kidney chromophobe, thyroid cancer and acute myeloid leukemia.
  • Higher PUS7 expression was associated with poorer outcomes in 11 cancer types, including mesothelioma (MESO). No hazard ratios or other numbers are given in the text.
  • High PUS7 expression was connected with shorter DFI (one of the survival measures used) in pancreatic cancer, liver cancer, sarcoma and endometrioid cancer. Mesothelioma is not listed for this measure.
  • In the osteosarcoma dataset GSE21257, higher PUS7 expression was significantly linked to poor outcomes.
  • PUS7 was significantly higher in osteosarcoma patients with metastases.
  • In the 10 paired hospital samples, tissue staining showed PUS7 significantly overexpressed in osteosarcoma compared with adjacent non-cancerous tissue.
  • In six cancer types, genes raised in the high-PUS7 group were enriched for cell-cycle and growth pathways such as the G2M checkpoint.
• The authors' conclusion: The authors concluded that PUS7 is a putative pan-cancer biomarker for prognosis, including in mesothelioma among 11 cancer types, and that PUS7 may control osteosarcoma initiation and progression.
• Limitations the authors state:
  • Few osteosarcoma sequencing datasets were available. The authors said more clinical cohorts are needed.

Topics

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

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