NK cell-associated longnon-coding RNAs reveal heterogeneity of colorectalcancer immune microenvironment

This study establishes a validated prognostic model based on NK cell-associated long noncoding RNAs (lncRNAs) to predict outcomes in colorectal cancer (CRC), a malignancy characterized by poor prognosis and limited response to conventional therapies. By integrating single-cell RNA-seq (GSE146771_Smartseq2) with TCGA-COAD/READ bulk transcriptomic data, NK-specific genes and correlated lncRNAs were identified. A multi-step analytical framework—univariate Cox regression for initial screening, LASSO regression to reduce overfitting, and multivariate Cox regression for final optimization—yielded a robust 16-lncRNA prognostic signature with high predictive accuracy. The model demonstrated strong performance across training and validation sets, as well as in 76 independent clinical samples. Mechanistically, AC010319.3, highly expressed in NK cells, was found to suppress NK cell cytotoxicity by downregulating IFN-γ and granzyme B expression, thereby promoting CRC cell proliferation and invasion. Overall, this work systematically elucidates the regulatory role of NK-associated lncRNAs in the CRC immune microenvironment and provides novel molecular targets and stratification strategies for CRC immunotherapy.

Yuxuan Li is a doctor. candidate in Gastrointestinal Surgery at Kunming Medical University, with clinical experience as a surgeon and a strong background in translational research. He has published multiple SCI papers as first author, co-first author, and co-corresponding author in journals such as Advanced Science and Frontiers in Immunology. His research focuses on immune mechanisms, lncRNA signatures, and metabolic reprogramming in digestive system tumors. He also holds one patent and is committed to integrating basic research with clinical practice