Identification of SGMS2 as a molecule involved in natural killer cell recruitment and its in-deep analysis in the liver cancer microenvironment: Evidence from large populations cohort

Background: Liver cancer, a common malignancy within the digestive system, presents with a particularly grim prognosis. Within the immune microenvironment, the role of natural killer (NK) cells in liver cancer remains unclear.

Methods: We sourced data on clinical parameters and gene expressions for liver cancer patients from The Cancer Genome Atlas Program database and carried out all analyses using R software and its relevant codes.

Results: In our research, we delved into the genes intertwined with NK cells in hepatocellular carcinoma (HCC). Leveraging the QUANTISEQ and MCPCOUNTER algorithms to quantify NK cells, we spotlighted genes vital to the recruitment of NK cells. Among these genes, GDE1, WDFY3, DNAJB14, PKD2, DGAT2, SGMS2 and MKNK2 showed a strong correlation with patient outcomes. We also mapped out the single-cell expression trajectories of these genes within the HCC milieu. From our findings, SGMS2 emerged as a key gene warranting further scrutiny. Our in-depth analysis of SGMS2 shed light on its influence over specific biological pathways, its contribution to the immune landscape and its role in genomic instability within HCC. Drawing from this, we formulated a predictive model rooted in SGMS2-associated genes. This model showcased remarkable precision across both training and validation cohorts.

Conclusions: Overall, our investigation underscored the profound implications of SGMS2, a gene pivotal to NK cell infiltration, in the landscape of HCC, thereby positioning it as a potential linchpin in oncological strategies.