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Tendomodulin in pan-cancer analysis: exploring its impact on immune modulation and uncovering functional insights in
Jingfeng Chen1,2, Qin Hu1, Cong Zhang3
1Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui, 323000, China.
Background:
Tendomodulin (TNMD) is pivotal in various malignancies, including colorectal cancer (CRC). However, its comprehensive impact across cancers, particularly its immunomodulatory function in CRC, remains underexplored. This study explored the role of TNMD in CRC by focusing on its immunomodulatory functions through comprehensive molecular and clinical analyses.
Methods:
Multiple bioinformatics databases and analytical tools were utilized for the TNMD in pan-cancer analysis. To validate the role of TNMD in CRC, we performed experiments, including immunofluorescence (IF), immunohistochemistry (IHC), real-time quantitative reverse transcription PCR (qPCR), western blotting, and cell migration assays.
Results:
TNMD expression and gene mutation vary across cancers and offer high diagnostic value. Survival analysis found that TNMD is associated with prognosis in multiple cancers. Notably, in patients with high microsatellite instability (MSI-H) CRC, TNMD expression correlated positively with various immune cells, particularly natural killer (NK) cells, whereas it was inversely correlated with regulatory T cells (Tregs). Crucially, in patients with microsatellite stability (MSS) CRC, high TNMD expression was associated with better immunotherapy outcomes, indicating its potential as a biomarker for patient stratification and tailored treatment approaches. Furthermore, single-cell sequencing data revealed stronger interactions between TNMD-positive tumor cells and fibroblasts or macrophages in the tumor microenvironment. Finally, TNMD was overexpressed in CRC tumor tissues and cell lines, thereby promoting invasion and metastasis.
Conclusions:
Our findings reveal a critical immunomodulatory role of TNMD in CRC, particularly in influencing tumor-immune interactions. Beyond its potential diagnostic and prognostic biomarker, TNMD promotes CRC metastasis and invasion, thus emerging as a promising therapeutic target. These findings highlight TNMD's significance in CRC and potentially other malignancies.
Insights
Tendomodulin (TNMD) influences colorectal cancer (CRC) by modulating immune cells and promoting metastasis. High TNMD expression in microsatellite-stable CRC predicts better immunotherapy response, identifying it as a potential therapeutic target.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tendomodulin (TNMD) is implicated in various cancers, but its specific immunomodulatory role in colorectal cancer (CRC) requires further investigation.
- Understanding TNMD's function in CRC is crucial for developing targeted therapies and improving patient outcomes.
Purpose of the Study:
- To comprehensively analyze the role of Tendonmodulin (TNMD) in colorectal cancer (CRC) and its immunomodulatory functions.
- To evaluate TNMD as a potential diagnostic, prognostic, and therapeutic biomarker in CRC.
Main Methods:
- Utilized bioinformatics databases for pan-cancer analysis of TNMD.
- Performed immunofluorescence, IHC, qPCR, western blotting, and cell migration assays to validate TNMD's role in CRC.
- Analyzed single-cell sequencing data to investigate tumor microenvironment interactions.
Main Results:
- TNMD expression exhibits diagnostic value and prognostic association across multiple cancers.
- In MSI-H CRC, TNMD correlates with increased NK cells and decreased Tregs; in MSS CRC, high TNMD predicts favorable immunotherapy outcomes.
- TNMD overexpression in CRC promotes tumor invasion and metastasis, with enhanced interactions with fibroblasts and macrophages.
Conclusions:
- Tendomodulin (TNMD) plays a critical immunomodulatory role in colorectal cancer (CRC), impacting tumor-immune cell interactions.
- TNMD serves as a potential diagnostic and prognostic biomarker and promotes CRC metastasis, positioning it as a promising therapeutic target.
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