Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 20;52(1):471.
doi: 10.1007/s11033-025-10559-3.

Sepsis-related immune signature C3 in endometrial carcinoma: implications for prognosis, tumor progression through bioinformatics and experimental validation

Kulsoom #  1 , Wajahat Ali #  2 , Saleem Ahmad  3 , Irfan Ali Khan  4 , Tanveen Kaur Soni  5 , Asia Masood  6 , Muhammad Omer Iqbal  7 , Valisher Sapayev Odilbek Uglu  8 , Mukhayya Xusinovna Djumaniyazova  9 , Anas Sameed Cholavaram  10 , Mubaraq Arisekola Abdulrahmon  11
Affiliations

Sepsis-related immune signature C3 in endometrial carcinoma: implications for prognosis, tumor progression through bioinformatics and experimental validation

Kulsoom et al. Mol Biol Rep. .

Erratum in

Abstract

Background: Sepsis and uterine corpus endometrial carcinoma (UCEC) share significant immunological and molecular pathways, particularly involving dysregulated inflammatory responses and immune modulation. Although sepsis-induced organ dysfunction is well studied, its role in cancer progression, particularly in UCEC, remains poorly understood.

Purpose: This study investigated the sepsis-related immune signature (SRIS) C3 in UCEC to uncover its role in tumor progression and metastasis.

Methods: RNA sequencing and clinical data from TCGA and GEO databases were analyzed using R software to identify DESRGs. Survival analysis, GO, KEGG pathway, and GSEA were performed to elucidate C3's biological functions. PPI networks, mutational analysis, methylation profiling, and immune infiltration analysis were conducted using various bioinformatics tools. MTT assays, RT-PCR, qPCR, and wound healing assays were performed to validate C3's function in HEC-1-B.

Results: Downregulation of C3 expression in UCEC was associated with enhanced inflammation, immune evasion, and metastatic potential, showing mechanisms observed in sepsis-induced organ dysfunction. Pathway enrichment analysis revealed significant activation of the NF-κB, JAK-STAT, and complement cascades, contributing to a pro-tumorigenic microenvironment. Mutational analysis showed a significant contribution to UCEC development. Protein-protein interaction analysis demonstrated a positive correlation with SRISs. These findings highlight the pivotal role of sepsis-related immune pathways, mainly C3, in driving UCEC progression.

Conclusion: Understanding the molecular interplay between sepsis-related immune responses and tumor progression may offer novel therapeutic opportunities. Specifically, targeting C3 may provide a new treatment strategy for UCEC patients with a history of sepsis, thereby improving clinical outcomes and guiding personalized therapeutic interventions.

Keywords: C3; Cancer immunology; Immune signature; Metastasis; Prognosis; Sepsis; Tumor progression; Uterine corpus endometrial carcinoma.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics declarations: This article contains no studies involving human participants or animals performed by authors. Competing interests: The authors declare no competing interests.

Similar articles

See all similar articles

References

    1. Morice P et al (2016) Endometrial cancer. Lancet 387(10023):1094–1108 - PubMed - DOI
    1. Abu-Rustum N et al (2023) Uterine neoplasms, version 1.2023, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 21(2):181–209 - PubMed - DOI
    1. Luthringer, M. and J. Marziale, Endometrial cancer treatment (PDQ®): Treatment-health professional information [NCI]. Diabetes. 21: p. 22.
    1. Cokkinides V et al (2005) American cancer society: Cancer facts and figures. American Cancer Society, Atlanta
    1. Wang X et al (2023) PHF6 promotes the progression of endometrial carcinoma by increasing cancer cells growth and decreasing T-cell infiltration. J Cell Mol Med 27(5):609–621 - PubMed - PMC - DOI

MeSH terms

LinkOut - more resources