NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

DARS , encoding for aspartyl-tRNA synthetase, is implicated in the pathogenesis of various cancers, including renal cell carcinoma, glioblastoma, colon cancer, and gastric cancer. Its role in BCR/ABL1 -negative myeloproliferative neoplasms (MPNs), however, remains unexplored. This study aimed to elucidate the expression of DARS in patients with MPNs (PV 23, ET 19, PMF 16) through immunohistochemical analysis and to examine the profiles of circulating immune cells and cytokines using flow cytometry. Our findings indicate a significant overexpression of DARS in all MPNs subtypes at the protein level compared to controls ( P < 0.05). Notably, elevated DARS expression was linked to splenomegaly in MPNs patients. The expression of DARS showed a negative correlation with CD4+ T cells (R = − 0.451, P = 0.0004) and CD4+ T/CD8+ T cell ratio (R = − 0.3758, P = 0.0040), as well as with CD68+ tumor-associated macrophages (R = 0.4037, P = 0.0017). Conversely, it was positively correlated with IL-2 (R = 0.5419, P < 0.001), IL-5 (R = 0.3161, P = 0.0166), IL-6 (R = 0.2992, P = 0.0238), and IFN-γ (R = 0.3873, P = 0.0029). These findings underscore a significant association between DARS expression in MPNs patients and specific clinical characteristics, as well as immune cell composition. Further investigation into the interplay between DARS and the immune microenvironment in MPNs could shed light on the underlying mechanisms of MPNs pathogenesis and immune dysregulation.

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Nucleolar protein interacting with the FHA domain of MKI67 may be an important factor in promoting the development of colorectal cancer: a comprehensive study integrating bulk RNA-seq, scRNA-seq, protein immunohistochemistry and CRISPR

Li,

Tang,

Chen

et al. 2024

Preprint

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Background Limited evidence suggests that nucleolar protein interacting with the FHA domain of MKI67 (NIFK) plays a significant role in tumour occurrence and development. The mechanism and clinical value of NIFK in colorectal cancer (CRC) still lack a comprehensive evaluation. Materials and Methods Cancerous tissue and paracancerous tissue of 266 CRC patients were collected for immunohistochemistry, and the mRNA expression profiles of 2262 CRC tissue and 1297 non-CRC tissue worldwide were collected and analysed at the NIFK protein and mRNA levels. Analyse the effect of knocking out NIFK by CRISPR on the growth status of CRC cells in 43 CRC cell lines. Enrichment analysis was used to explore the potential biological behaviour of NIFK in the CRC. The impact of NIFK on the immune microenvironment and single-cell landscape of CRC tissue was also analysed. In addition, the clinical value of NIFK in CRC was also evaluated in terms of clinical pathology, targeted therapy, and immunotherapy. Results The expression levels of NIFK protein (p < 0.05) and mRNA (SMD = 2.13, p < 0.05) in CRC were significantly higher than those in non-CRC. CRC cells exhibit a strong requirement for NIFK for growth. Abnormal expression of NIFK may affect the progression of CRC by affecting the GALECTIN, ANGPTL, and GDF signalling pathways of malignant epithelial cells, the MIF signalling pathway of T cells, and the TGFb signalling pathway of NK cells. The high expression of NIFK protein and mRNA has a strong ability to identify CRC. Conclusion NIFK plays an important role in the occurrence and development of CRC. NIFK may promote the occurrence and development of CRC through the cell cycle, ribosome, and mitochondrial pathways. The T-cell MIF pathway may have certain clinical value in anti-tumour therapy.

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NIFK as a potential prognostic biomarker in colorectal cancer correlating with immune infiltrates

Cited by 3 publications

References 38 publications

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E3 Ubiquitination Ligase MYLIP Mediates the NKRF/SLC25A34 Axis to Suppress Malignant Progression in Colorectal Cancer

DARS expression in BCR/ABL1-negative myeloproliferative neoplasms and its association with the immune microenvironment

Nucleolar protein interacting with the FHA domain of MKI67 may be an important factor in promoting the development of colorectal cancer: a comprehensive study integrating bulk RNA-seq, scRNA-seq, protein immunohistochemistry and CRISPR

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