Significance of monocyte infiltration in patients with gastric cancer: A combined study based on single cell sequencing and TCGA

Abstract

BackgroundGastric cancer is still one of the most lethal tumor diseases in the world. Despite some improvements, the prognosis of patients with gastric cancer is still not accurately predicted.MethodsBased on single cell sequencing data, we conducted a detailed analysis of gastric cancer patients and normal tissues to determine the role of monocytes in the progression of gastric cancer. WCGA facilitated our search for Grade-related genes in TCGA. Then, according to the marker genes and cell differentiation genes of monocytes, we determined the cancer-promoting genes of monocytes. Based on LASSO regression, we established a prognostic model using TCGA database. The accuracy of the model was verified by PCA, ROC curve, survival analysis and prognostic analysis. Finally, we evaluated the significance of the model in clinical diagnosis and treatment by observing drug sensitivity, immune microenvironment and immune checkpoint expression in patients with different risk groups.ResultsMonocytes were poorly differentiated in tumor microenvironment. It mainly played a role in promoting cancer in two ways. One was to promote tumor progression indirectly by interacting with other tumor stromal cells. The other was to directly connect with tumor cells through the MIF and TNF pathway to play a tumor-promoting role. The former was more important in these two ways. A total of 292 monocyte tumor-promoting genes were obtained, and 12 genes were finally included in the construction of the prognosis model. A variety of validation methods showed that our model had an accurate prediction ability. Drug sensitivity analysis could provide guidance for clinical medication of patients. The results of immune microenvironment and immune checkpoint also indicated the reasons for poor prognosis of high-risk patients.ConclusionIn conclusion, we provided a 12-gene risk score formula and nomogram for gastric cancer patients to assist clinical drug therapy and prognosis prediction. This model had good accuracy and clinical significance.

Mapping the tumor microenvironment in clear cell renal carcinoma by single-cell transcriptome analysis

“…In concurrence, Kim et al identified a propensity of monocytes to undergo a phenotypic shift towards an anti-inflammatory state in the context of metastatic lung adenocarcinoma, thereby facilitating the establishment of an inhibitory immune microenvironment ( Kim et al, 2020 ). Similarly, Xu et al observed impaired monocyte differentiation within the tumor microenvironment of gastric cancer, whereby these cells engage in intercellular communication with tumor stromal cells or neoplastic cells, promoting tumor progression ( Xu W. et al, 2022 ). Therefore, the activation of monocytes via immunotherapy could be a promising treatment strategy.…”

MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy

“…In non-smallcell lung cancer, a higher baseline serum MIF protein level is a weak prognostic marker of worse progression-free survival after anti-PD-1 ICB treatment but does not predict overall survival [87], and a similar trend has been shown in melanoma [12], corroborating the inverse correlation between MIF expression and patient response to ICB therapy. In addition to the research directly investigating MIF as a biomarker, recent studies have suggested a potential mechanistic role for MIF in ICB treatment response via monocytes in gastric cancer [88] and through metabolic reprogramming in a breast cancer stem cell line [89]. Future work should elucidate the cell-type-specific mechanisms of MIF in tumor control and patient response to ICB therapy.…”