Open Access

ARTICLE

IL1A: a novel prognostic biomarker and potential therapeutic target for renal clear cell carcinoma

JI ZENG^1,2,3,#, XUETENG MENG^1,3,#, YUAN ZHANG^1,3, JUN LI¹, TAOTAO MA^1,3,4, CHENG HUANG^1,3,*

1 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China
2 Department of Pharmacy, Ma’anshan City Hospital of Traditional Chinese Medicine, Ma’anshan, 243000, China
3 Anhui Provincial Institute of Translation Medicine, Anhui Medical University, Hefei, 230032, China
4 The Third Affiliated Hospital of Anhui Medical University, The First People’s Hospital of Hefei, Hefei, 230032, China

* Corresponding Author: CHENG HUANG. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis)

Oncology Research 2025, 33(7), 1739-1755. https://doi.org/10.32604/or.2025.061978

Received 07 December 2024; Accepted 05 March 2025; Issue published 26 June 2025

Abstract

Background: Renal cell carcinoma (RCC) is a prevalent malignancy characterized by a rising incidence and significant mortality. Interleukins (ILs) are crucial in regulating immune cell trafficking and exhibit anti-tumor properties. However, limited research has explored the expression levels and prognostic significance of interleukins in RCC. Methods: In this comprehensive study, we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools, including Oncomine, UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST, STRING, and Linked Omics. Results: Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4, IL7, IL15, IL16, IL23A, IL26, and IL32 were significantly upregulated in RCC tissues, indicating their potential involvement in the pathogenesis of this malignancy. In contrast, IL1A, IL11, and IL27 were downregulated, indicating their potential function as tumor suppressors. Significant correlations were identified between the expression levels of IL11, IL23A, IL27, IL32, and the pathological stage of RCC patients. The expression levels of IL1A, IL4, IL11, IL15, IL16, IL23A, IL26, IL27, and IL32 were significantly correlated with improved prognosis. The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways. homeobox A10 (HOXA10), v-myb myeloblastosis viral oncogene homolog (avian) (MYB), v-rel reticuloendotheliosis viral oncogene homolog A (avian) (RELA), and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1) are key transcription factors for ILs, while LCK proto-oncogene (LCK), LYN proto-oncogene (LYN), spleen associated tyrosine kinase (SYK), Janus kinase 3 (JAK3), and FER tyrosine kinase (FER) are IL targets. IL expression significantly correlated with the infiltration of six distinct immune cell types. IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps (NETs). Additionally, NFKB1 may positively regulate IL1A, providing a rationale for further in vivo and clinical studies. Conclusion: In conclusion, our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent in vivo and clinical investigations.

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Supplementary Material

Supplementary Material File

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