Dataset Information

SEMA6A inhibits tumor progression and boosts anti-tumor immunity via blocking the ISG15/TGFβ axis in colorectal cancer

ABSTRACT: Semaphorin is an axon-guiding factor regulating nervous system development. A growing body of evidence shows that semaphorin could regulate tumor progress and immune responses. The research found that Semaphorin 6A (SEMA6A) may play a dual role in the occurrence and development of tumors. Nevertheless, the regulatory role of SEMA6A in colorectal cancer (CRC) remains unclear. This study aimed to investigate the prognostic value, expression pattern, clinical significance, and immune effects of SEMA6A in CRC. Through multi-database analyses and validation with clinical specimens and tissue microarray, we identified reduced SEMA6A expression in CRC tissues, establishing it as an independent prognostic factor. Functional enrichment and immune infiltration analyses revealed SEMA6A's protective role through tumor immune microenvironment modulation, with elevated expression correlating with enhanced immune cell infiltration. Cellular experiments including CCK8, Transwell, and immunofluorescence assay demonstrated SEMA6A can suppress the proliferation, migration, and invasion ability of CRC. Integrated RNA-seq and proteomic analyses, we identified ISG15 as a downstream effector of SEMA6A. Functional validation confirmed that ISG15 promotes malignant progression and counteracts SEMA6A-mediated tumor suppression. Coculture experiments revealed that SEMA6A can activate the CD8+ T cells and inhibit the expression of TGF-β1 by reducing the expression level of ISG15. Moreover, SEMA6A could induce the response of CRC to PD-1 monoclonal antibody by up-regulating immunostimulatory factors, thus playing an anti-tumor role in a subcutaneous CRC model. Our findings indicate that SEMA6A can stratify the risk of CRC patients and serve as a novel biomarker to predict response to immunotherapy, providing novel insights into precision medicine and immunotherapeutic strategies for CRC.

ORGANISM(S): Mus musculus

PROVIDER: GSE298450 | GEO | 2026/06/24

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, with stage II CRC patients presenting unique challenges due to their heterogeneous outcomes. Despite curative surgical resection, 15-20% of stage II CRC patients experience recurrence within five years of diagnosis. Current prognostic models, based on clinicopathologic features such as vascular invasion, poor differentiation, and adverse molecular profiles, lack precision in predicting recurrence, highlighting the need for other complementary tools. Advances in proteomics have positioned formalin-fixed paraffin-embedded (FFPE) tissues and small extracellular vesicles (sEVs) as promising sources for biomarker identification. FFPE tissues offer a wealth of retrospective diagnostic material, while sEVs, particularly exosomes, encapsulate tumor-derived proteins and nucleic acids, providing minimally invasive insights into the tumor microenvironment. Proteomic profiling of these samples should allow the identification of molecular alterations linked to tumor aggressiveness and recurrence, paving the way for novel diagnostic and prognostic applications. In this study, we here combine proteomics analyses of paired FFPE tissues and sEVs to identify stage II CRC associated biomarkers and tumor biopsies, plasma of CRC patients and controls, and immunohistochemistry and in vitro and in vivo analyses to validate proteomics results. Among the identified candidates, CDCA2 emerged as a interesting driver of tumor formation, progression, and metastasis in CRC. Transient knockdown experiments demonstrated that its depletion impaired key tumorigenic processes, including proliferation, adhesion, migration, and invasion. Additionally, this study validated MANF as a plasma biomarker capable of distinguishing recurrent from non-recurrent CRC patients, offering potential for improving patient stratification and personalized treatment strategies in combination with other markers. Interestingly, our multifaceted approach allowed the identification of dysregulated proteins associated to CRC recurrence.

Dataset Information

SEMA6A inhibits tumor progression and boosts anti-tumor immunity via blocking the ISG15/TGFβ axis in colorectal cancer

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets