Effects of Hypoxia in Intestinal Tumors on Immune Cell Behavior in the Tumor Microenvironment

et al. 2022

Front. Cell Dev. Biol.

There is evidence suggesting that immune genes play pivotal roles in the development and progression of colorectal cancer (CRC). Colorectal carcinoma patient data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were randomly classified into a training set, a test set, and an external validation set. Differentially expressed gene (DEG) analyses, univariate Cox regression, and the least absolute shrinkage and selection operator (LASSO) were used to identify survival-associated immune genes and develop a prognosis model. Receiver operating characteristic (ROC) analysis and principal component analysis (PCA) were used to evaluate the discrimination of the risk models. The model genes predicted were verified using the Human Protein Atlas (HPA) databases, colorectal cell lines, and fresh CRC and adjacent tissues. To understand the relationship between IRGs and immune invasion and the TME, we analyzed the content of immune cells and scored the TME using CIBERSORT and ESTIMATE algorithms. Finally, we predicted the potential sensitive chemotherapeutic drugs in different risk score groups by the Genomics of Drug Sensitivity in Cancer (GDSC). A total of 491 IRGs were screened, and 14 IRGs were identified to be significantly related to overall survival (OS) and applied to construct an immune-related gene (IRG) prognostic signature (IRGSig) for CRC patients. Calibration plots showed that nomograms have powerful predictive ability. PCA and ROC analysis further verified the predictive value of this fourteen-gene prognostic model in three independent databases. Furthermore, we discovered that the tumor microenvironment changed significantly during the tumor development process, from early to middle to late stage, which may be an essential factor for tumor deterioration. Finally, we selected six commonly used chemotherapeutic drugs that have the potential to be useful in the treatment of CRC. Altogether, immune genes were used to construct a prognosis model for CRC patients, and a variety of methods were used to test the accuracy of this model. In addition, we explored the immune mechanisms of CRC through immune cell infiltration and TME in CRC. Furthermore, we assessed the therapeutic sensitivity of many commonly used chemotherapeutic medicines in individuals with varying risk factors. Finally, the immune risk model and immune mechanism of CRC were thoroughly investigated in this paper.

Section: Discussionsupporting

confidence: 93%

A Prognostic Model Using Immune-Related Genes for Colorectal Cancer

Wei

Zhang

et al. 2022

Front. Cell Dev. Biol.

“…In addition to hypoxia-mediated resistance to standard therapies, regulation of gene and protein expression, genetic instability, and malignant progression, hypoxia also plays a key role in anticancer immune response [ 9 ]. At present, the common treatment methods of oral cancer include surgery, radiotherapy, chemotherapy and anti-EGFR drugs [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Establishment and Analysis of Hypoxia-Related Model in Oral Squamous Cell Carcinoma

Journal of Healthcare Engineering

2022

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world. Hypoxia is closely related to immunity in tumor microenvironment and also affects the prognosis of patients. However, there is still a lack of articles related to tumor hypoxia in oral squamous cell carcinoma. Therefore, we aimed to develop a hypoxia model for future application in patient prognosis analysis and immunotherapy. The transcriptome and survival information of OSCC were downloaded from GEO database. The Cox regression model of the lasso method was used to identify prognostic genes and develop gene characteristics based on hypoxia immunity. According to the median risk value, the patients were divided into high-risk group and low-risk group. Then, the estimated algorithm was used to estimate the relationship between hypoxia and immune status. At the same time, we evaluated the correlation and expression differences of immune-related genes between different risk groups. By using the lasso model, we identified two genes, including PFKP and SERPINE1, to construct gene signatures for risk stratification. We observed that both genes were highly expressed in the high-risk group, which was not conducive to the prognosis of the tumor. In addition, in the analysis of the degree of immune infiltration, we observed that there were differences in the content of a variety of immune cells between the two groups. It can be seen that there were great differences in the immune cells constituting the tumor microenvironment in oral squamous cell carcinoma. There remain significant differences in the expression levels of multitudinous immune-related genes. These immune-related genes include CCL chemokines, Chemokine (C-X-C motif) ligand (CXCL), CD antigens, HSP family, interferon family, and interleukin family. The hypoxia-immune-based gene signature represents a promising tool for risk stratification tool in oral squamous cell carcinoma cancer. It might serve as a prognostic classifier for clinical decision-making regarding individualized prognostication and treatment and follow-up scheduling.

“…The relative abundance of each type of immune cell was calculated by the algorithm of CIBERSORT R script v1.03 ( 27 ). CIBERSORT is widely used to calculate the proportion of immune cell infiltration in the TME of solid tumors ( 28 – 31 ).…”

Section: Methodsmentioning

confidence: 99%

Transmembrane Protein-Based Risk Model and H3K4me3 Modification Characteristics in Lung Adenocarcinoma

Fan

et al. 2022

Front. Oncol.

The role and mechanism of transmembrane proteins (TMEMs) in tumorigenesis remain unclear. Based on 4 independent cohorts containing 1,208 cases, we identified 3 TMEMs (TMEM273, TMEM164, and TMEM125), which were used to construct a risk model to predict the prognosis of LUAD. The two patterns based on the risk score exhibited a high degree of consistency with the characteristics of immune cell infiltration and epigenetic distribution. Patients with a low-risk score, characterized by an increased activation of immunity, H3K4me3 modification, tumor cell apoptosis, chemokine secretion, and TMB, had better disease-free survival (DFS) and overall survival (OS). Obvious immunosuppression, increased epithelial–mesenchymal transition, a low H3K4me3 level, shortened cell cycle, and accelerated cell division manifested in high-risk patients, with poorer DFS and OS. The model showed a better prognostic value than the tumor immune dysfunction and exclusion score. Correlation analysis told us that patients with high scores were suitable for treatment with CD276 inhibitors for their higher levels of CD276 expression. The risk score had a strong negative correlation with HAVCR2 and ICOS among patients with EGFR-WT, KRAS-WT, STK11-WT, or TP53-MUT, and patients with these mutation types with low scores were suitable for treatment with HAVCR2 or ICOS inhibitors. This work comprehensively analyzed the role and mechanism of TMEMs in LUAD and revealed the characteristics of histone methylation modification. The TMEM-based signature gave us deep insight into immune cell infiltration profiles and provided an individualized immunotherapy strategy.