ArticleEuropean journal of medical research2023
An integrative evaluation of circadian gene TIMELESS as a pan-cancer immunological and predictive biomarker.
Article in European journal of medical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- TIMELESS promotes glioma stemness and malignancy through JAK-STAT3 pathway.The Journal of biological chemistry · 2026Article
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- TIMELESS as a prognostic biomarker and therapeutic target in gastric cancer.Journal, genetic engineering & biotechnology · 2025Article
- RPS27A as a potential clock-related diagnostic biomarker for myocardial infarction: Comprehensive bioinformatics analysis and experimental validation.Clinics (Sao Paulo, Brazil) · 2025Article
- Circadian rhythms and breast cancer: unraveling the biological clock's role in tumor microenvironment and ageing.Frontiers in immunology · 2024Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe gene TIMELESS, which is involved in the circadian clock and the cell cycle, has recently been linked to various human cancers. Nevertheless, the association between TIMELESS expression and the prognosis of individuals afflicted with pan-cancer remains largely unknown.
objectivesThe present study aims to exhaustively scrutinize the expression patterns, functional attributes, prognostic implications, and immunological contributions of TIMELESS across diverse types of human cancer.
methodsThe expression of TIMELESS in normal and malignant tissues was examined, as well as their clinicopathologic and survival data. The characteristics of genetic alteration and molecular subtypes of cancers were also investigated. In addition, the relationship of TIMELESS with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity was illustrated. Immunohistochemistry (IHC) was used to validate the expression of TIMELESS in clinical patients with several types of cancer.
resultsIn contrast to the matching normal controls, most tumor types were found to often overexpress TIMELESS. Abnormal expression of TIMELESS was significantly related to more advanced tumor stage and poorer prognosis of breast cancer, as well as infiltrating immune cells such as cancer-associated fibroblast infiltration in various tumors. Multiple cancer types exhibited abnormal expression of TIMELESS, which was also highly correlated with MSI and TMB. More crucially, TIMELESS showed promise in predicting the effectiveness of immunotherapy and medication sensitivity in cancer therapy. Moreover, cell cycle, DNA replication, circadian rhythm, and mismatch repair were involved in the functional mechanisms of TIMELESS on carcinogenesis. Furthermore, immunohistochemical results manifested that the TIMELESS expression was abnormal in some cancers.
conclusionsThis study provides new insights into the link between the circadian gene TIMELESS and the development of various malignant tumors. The findings suggest that TIMELESS could be a prospective prognostic and immunological biomarker for pan-cancer.
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