Deciphering anoikis resistance and identifying prognostic biomarkers in clear cell renal cell carcinoma epithelial cells

Sep 21, 2026

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Study focuses on clear cell renal cell carcinoma (ccRCC) where prognosis and management remain challenging despite multimodal therapies. The work investigates anoikis, a programmed cell death process crucial to tumor progression and metastasis, by profiling anoikis-related genes (ARGs) and their epithelial subclusters. Single-cell RNA sequencing from seven ccRCC patients and six GEO microarray datasets were integrated to detect differentially expressed genes. A LASSO and multivariate Cox risk model was built, validated through BEST, ULCAN, and RT-PCR, and visualized as a clinical nomogram with pathway, immune infiltration, spatial and drug-sensitivity analyses. Key prognostic genes TIMP1, PECAM1, and CDKN1A were linked to higher immune infiltration and increased anoikis resistance in the high-risk group.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Materials and methods

Data collection and research design

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Deciphering anoikis resistance and identifying prognostic biomarkers in clear cell renal cell carcinoma epithelial cells Junyi Li, Qingfei Cao & Ming Tong* This study tackles the persistent prognostic and management challenges of clear cell renal cell carcinoma (ccRCC), despite advancements in multimodal therapies. Focusing on anoikis, a critical form of programmed cell death in tumor progression and metastasis, we investigated its resistance in cancer evolution. Using single-cell RNA sequencing from seven ccRCC patients, we assessed the impact of anoikis-related genes (ARGs) and identified differentially expressed genes (DEGs) inAnoikisrelated epithelial subclusters (ARESs). Additionally, six ccRCC RNA microarray datasets from the GEO database were analyzed for robust DEGs. A novel risk prognostic model was developed through LASSO and multivariate Cox regression, validated using BEST, ULCAN, and RT-PCR. The study included functional enrichment, immune infiltration analysis in the tumor microenvironment (TME), and drug sensitivity assessments, leading to a predictive nomogram integrating clinical parameters. Results highlighted dynamic ARG expression patterns and enhanced intercellular interactions in ARESs, with significant KEGG pathway enrichment in MYC + Epithelial subclusters indicating enhanced anoikis resistance. Additionally, all ARESs were identified in the spatial context, and their locational relationships were explored. Three key prognostic genes—TIMP1, PECAM1, and CDKN1A—were identified, with the high-risk group showing greater immune infiltration and anoikis resistance, linked to poorer prognosis. This study offers a novel ccRCC risk signature, providing innovative approaches for patient management, prognosis, and personalized treatment. Renal cell carcinoma (RCC), recognized as the third most common urological malignancy, poses significant challenges in clinical and scientific domains for urologists. In 2020, over 400,000 new RCC cases were documented globally. ccRCC, the predominant subtype of RCC, constitutes about 70–80% of all RCC cases1,2. Characterized by high metastasis and mortality rates, ccRCC is increasingly diagnosed in younger populations3. In 2022, China reported 77,410 new RCC cases and 46,345 deaths4. Although partial and radical nephrectomies are the primary ccRCC treatments, surgical intervention often doesn’t prevent recurrence in early-stage cases5,6. The prognosis for ccRCC patients remains relatively poor. Early-stage ccRCC often presents without distinct clinical symptoms, resulting in approximately 30% of patients receiving a diagnosis at advanced stages, characterized by distant metastasis and consequently missing opportunities for surgical intervention7. This underscores the critical need for innovative diagnostic and prognostic models, alongside the development of new biomarkers and molecular targets for ccRCC. Anoikis, a unique form of programmed cell death, is triggered when cells detach from adjacent cells or the extracellular matrix they typically adhere to. This mechanism is pivotal in the regulation of cellular survival, functioning by selectively eliminating cells that have abnormally detached from the adjacent structure8. Anoikis acts as a significant protective factor in both cancerous and non-cancerous diseases, particularly in inhibiting the dissemination of cancer cells that could lead to distant metastases9. Epithelial cells, which preserve normal tissue architecture through intercellular adhesion and engagement with the extracellular matrix, are particularly prone to anoikis10. Furthermore, epithelial cells constitute a critical component of tumor tissue. Tumor-Associated Epithelial Cells (TECs), in contrast to their normal counterparts, demonstrate resistance to anoikis, a critical precondition for tumor metastasis11. Anchorage-independent growth and the Epithelial-Mesenchymal Transiti

FAQs

What problem does the study address in clear cell renal cell carcinoma (ccRCC)?

It targets persistent prognostic and management challenges in ccRCC despite multimodal therapies, focusing on how anoikis-related mechanisms influence tumor evolution and outcomes.

How was anoikis-related biology analyzed in the research?

The study used single-cell RNA sequencing from seven ccRCC patients to assess anoikis-related genes (ARGs), and it also analyzed six ccRCC GEO microarray datasets to identify robust differentially expressed genes across epithelial subclusters.

Which genes were identified as key prognostic markers and what was their clinical implication?

TIMP1, PECAM1, and CDKN1A were identified as key prognostic genes; the high-risk group showed greater immune infiltration and increased anoikis resistance, associated with poorer prognosis.

Sep 21, 2026

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