scholarly journals Immune-Related Genes: Potential Prognostic Factors and Regulatory Targets for Cervical Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Feng Xie ◽  
Xiaofeng Liu ◽  
Hua Liu ◽  
Min Wei ◽  
Wei Liu

Background. Advanced cervical carcinoma carries a particularly poor prognosis, and few treatment options exist. It is very important to find a method to evaluate the prognosis and survival rate of cervical carcinoma. The metastasis and invasion of cervical carcinoma are closely related to tumor immune microenvironment (TIME), and immune related genes (IRGs) are involved in the regulation of TIME. However, the role of IRGs in the prognosis of patients with cervical carcinoma remains unclear. Methods. The gene expression profiles of cervical carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and IRG information were obtained from the ImmPort database. The IRGs were screened by coexpression analysis and were also performed function enrichment and pathway analyses. A prognosis model was built based on IRGs, and the risk score (RS) was calculated by Cox regression analysis. The accuracy was assessed by receiver operating characteristic (ROC) curve analysis. Besides, the relationship between RS and TIMER-generating immune cell content was performed by immune infiltration analysis. Results. In a total of 2503 differentially expressed genes (DEGs), 204 genes were IRGs, 20 of which were crucially correlated with the survival rate of cervical carcinoma. On the basis of Cox regression analysis, 6 IRGs were included in the prognosis model to calculate the RS. Kaplan-Meier survival and ROC analyses showed that the prognostic function of the model was superior to the current model constructed by clinicopathological risk factors. In addition, these 6 IRG signatures were related to the immune infiltration levels of six immune cells and the overall survival (OS) of cervical carcinoma. Finally, C-terminal Src kinase (CSK) gene is related to tumor metastasis, and Slit guidance ligand 2 (Slit2) is related to tumor clinical stage. Conclusion. The IRGs may contribute to the stratification of prognosis, and CSK/Slit2 may be two suppressor genes for cervical carcinoma.

2020 ◽  
Author(s):  
Xing Chen ◽  
Junjie Zheng ◽  
Min ling Zhuo ◽  
Ailong Zhang ◽  
Zhenhui You

Abstract Background: Breast cancer (BRCA) represents the most common malignancy among women worldwide that with high mortality. Radiotherapy is a prevalent therapeutic for BRCA that with heterogeneous effectiveness among patients. Methods: we proposed to develop a gene expression-based signature for BRCA radiotherapy sensitivity prediction. Gene expression profiles of BRCA samples from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were obtained and used as training and independent testing dataset, respectively. Differential expression genes (DEGs) in BRCA tumor samples compared with their paracancerous samples in the training set were identified by using edgeR Bioconductor package followed by dimensionality reduction through autoencoder method and univariate Cox regression analysis to screen genes among DEGs that with significant prognosis significance in patients that were previously treated with radiation. LASSO Cox regression method was applied to screen optimal genes for constructing radiotherapy sensitivity prediction signature. Results: 603 DEGs were obtained in BRCA tumor samples, and seven out of which were retained after univariate cox regression analysis. LASSO Cox regression analysis finally remained six genes based on which the radiotherapy sensitivity prediction model was constructed. The signature was proved to be robust in both training and independent testing sets and an independent marker for BRCA radiotherapy sensitivity prediction. Conclusions: this study should be helpful for BRCA patients’ therapeutics selection and clinical decision.


2020 ◽  
Vol 10 ◽  
Author(s):  
Quanwei Zhou ◽  
Xuejun Yan ◽  
Weidong Liu ◽  
Wen Yin ◽  
Hongjuan Xu ◽  
...  

Diffuse glioma is one of the most prevalent malignancies of the brain, with high heterogeneity of tumor-infiltrating immune cells. However, immune-associated subtypes of diffuse glioma have not been determined, nor has the effect of different immune-associated subtypes on disease prognosis and immune infiltration of diffuse glioma patients. We retrieved the expression profiles of immune-related genes from The Cancer Genome Atlas (TCGA) (n = 672) and GSE16011 (n = 268) cohorts and used them to identify subtypes of diffuse glioma via Consensus Cluster Plus analysis. We used the limma, clusterProfiler, ESTIMATE, and survival packages of R for differential analysis, functional enrichment, immune and stromal score evaluation respectively in three subtypes, and performed log-rank tests in immune subtypes of diffuse glioma. The immune-associated features of diffuse glioma in the two cohorts were characterized via bioinformatic analyses of the mRNA expression data of immune-related genes. Three subtypes (C1–3) of diffuse glioma were identified from TCGA data, and were verified using the GSE16011 cohort. We then evaluated their immune characteristics and clinical features. Our mRNA profiling analyses indicated that the different subtypes of diffuse glioma presented differential expression profile of specific genes and signal pathways in the TCGA cohort. Patients with subtype C1, who were mostly diagnosed with grade IV glioma, had poorer outcomes than patients with subtype C2 or C3. Subtype C1 was characterized by a higher degree of immune cell infiltration as estimated by GSVA, and more frequent wildtype IDH1. By contrast, subtype C3 included more grade II and IDH1-mutated glioma, and was associated with more infiltration of CD4+T cells. Most subtype C2 had the features between subtypes C1 and C3. Meanwhile, immune checkpoints and their ligand molecules, including PD1/(PD-L1/PDL2), CTLA4/(CD80/CD86), and B7H3/TLT2, were significantly upregulated in subtype C1 and downregulated in subtype C3. In addition, patients with subtype C1 exhibited more frequent gene mutations. Univariate and multivariate Cox regression analyses revealed that diffuse glioma subtype was an effective, independent, and better prognostic factor. Therefore, we established a novel immune-related classification of diffuse glioma, which provides potential immunotherapy targets for diffuse glioma.


2022 ◽  
Author(s):  
Thongher Lia ◽  
Yanxiang Shao ◽  
Parbatraj Regmi ◽  
Xiang Li

Bladder cancer is one of the highly heterogeneous disorders accompanied by a poor prognosis. This study aimed to construct a model based on pyroptosis‑related lncRNA to evaluate the potential prognostic application in bladder cancer. The mRNA expression profiles of bladder cancer patients and corresponding clinical data were downloaded from the public database from The Cancer Genome Atlas (TCGA). Pyroptosis‑related lncRNAs were identified by utilizing a co-expression network of Pyroptosis‑related genes and lncRNAs. The lncRNA was further screened by univariate Cox regression analysis. Finally, 8 pyroptosis-related lncRNA markers were established using Lasso regression and multivariate Cox regression analysis. Patients were separated into high and low-risk groups based on the performance value of the median risk score. Patients in the high-risk group had significantly poorer overall survival (OS) than those in the low-risk group (p < 0.001), and In multivariate Cox regression analysis, the risk score was an independent predictive factor of OS ( HR>1, P<0.01). The area under the curve (AUC) of the 3- and 5-year OS in the receiver operating characteristic (ROC) curve were 0.742 and 0.739 respectively. In conclusion, these 8 pyroptosis-related lncRNA and their markers may be potential molecular markers and therapeutic targets for bladder cancer patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dankun Luo ◽  
Wenchao Yao ◽  
Qiang Wang ◽  
Qiu Yang ◽  
Xuxu Liu ◽  
...  

AbstractLong non-coding RNA (lncRNA) is a prognostic biomarker for many types of cancer. Here, we aimed to study the prognostic value of lncRNA in Breast Invasive Carcinoma (BRCA). We downloaded expression profiles from The Cancer Genome Atlas (TCGA) datasets. Subsequently, we screened the differentially expressed genes between normal tissues and tumor tissues. Univariate Cox, LASSO regression, and multivariate Cox regression analysis were used to construct a lncRNA prognostic model. Finally, a nomogram based on the lncRNAs model was developed, and weighted gene co-expression network analysis (WGCNA) was used to predict mRNAs related to the model, and to perform function and pathway enrichment. We constructed a 6-lncRNA prognostic model. Univariate and multivariate Cox regression analysis showed that the 6-lncRNA model could be used as an independent prognostic factor for BRCA patients. We developed a nomogram based on the lncRNAs model and age, and showed good performance in predicting the survival rates of BRCA patients. Also, functional pathway enrichment analysis showed that genes related to the model were enriched in cell cycle-related pathways. Tumor immune infiltration analysis showed that the types of immune cells and their expression levels in the high-risk group were significantly different from those in the low-risk group. In general, the 6-lncRNA prognostic model and nomogram could be used as a practical and reliable prognostic tool for invasive breast cancer.


2020 ◽  
Vol 11 ◽  
Author(s):  
Hao Zuo ◽  
Luojun Chen ◽  
Na Li ◽  
Qibin Song

Pancreatic cancer is known as “the king of cancer,” and ubiquitination/deubiquitination-related genes are key contributors to its development. Our study aimed to identify ubiquitination/deubiquitination-related genes associated with the prognosis of pancreatic cancer patients by the bioinformatics method and then construct a risk model. In this study, the gene expression profiles and clinical data of pancreatic cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database and the Genotype-tissue Expression (GTEx) database. Ubiquitination/deubiquitination-related genes were obtained from the gene set enrichment analysis (GSEA). Univariate Cox regression analysis was used to identify differentially expressed ubiquitination-related genes selected from GSEA which were associated with the prognosis of pancreatic cancer patients. Using multivariate Cox regression analysis, we detected eight optimal ubiquitination-related genes (RNF7, NPEPPS, NCCRP1, BRCA1, TRIM37, RNF25, CDC27, and UBE2H) and then used them to construct a risk model to predict the prognosis of pancreatic cancer patients. Finally, the eight risk genes were validated by the Human Protein Atlas (HPA) database, the results showed that the protein expression level of the eight genes was generally consistent with those at the transcriptional level. Our findings suggest the risk model constructed from these eight ubiquitination-related genes can accurately and reliably predict the prognosis of pancreatic cancer patients. These eight genes have the potential to be further studied as new biomarkers or therapeutic targets for pancreatic cancer.


2020 ◽  
Author(s):  
Leilei Wang ◽  
Weile Gu ◽  
Huijun Ni

Abstract Papillary renal cell carcinoma (PRCC) is the second most common type of renal carcinoma following clear cell renal cell carcinoma, and the role of immune-related genes (IRGs) in tumorigenesis and metastasis is evident; its prognostic value in PRCC remains unclear. In this study, we downloaded the gene expression profiles and clinical data of patients with PRCC from The Cancer Genome Atlas (TCGA) database and obtained IRGs from the ImmPort database. A total of 371 differentially expressed IRGs (DEIRGs) were discovered between PRCC and normal kidney tissues. Prognostic DEIRGs (PDEIRGs) were identified by univariate Cox regression analysis. Then, we screened the four most representative PDEIRGs (IL13RA2, CCL19, BIRC5, and INHBE) and used them to construct a risk model to predict the prognosis of patients with PRCC. This model precisely stratified survival outcome and accurately identified mutation burden in PRCC. Thus, our results suggest that these four PDEIRGs are available prognostic predictors for PRCC. They could be used to assess the prognosis and to guide individualized treatments for patients with PRCC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jin-Cheng Guo ◽  
Qing-Shuang Wei ◽  
Lei Dong ◽  
Shuang-Sang Fang ◽  
Feng Li ◽  
...  

Background: Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed.Methods: Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan–Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed.Results: Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group (n = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank P < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis (n = 431, Log Rank P < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis.Conclusions: We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xu Wang ◽  
Yuanmin Xu ◽  
Ting Li ◽  
Bo Chen ◽  
Wenqi Yang

Abstract Background Autophagy is an orderly catabolic process for degrading and removing unnecessary or dysfunctional cellular components such as proteins and organelles. Although autophagy is known to play an important role in various types of cancer, the effects of autophagy-related genes (ARGs) on colon cancer have not been well studied. Methods Expression profiles from ARGs in 457 colon cancer patients were retrieved from the TCGA database (https://portal.gdc.cancer.gov). Differentially expressed ARGs and ARGs related to overall patient survival were identified. Cox proportional-hazard models were used to investigate the association between ARG expression profiles and patient prognosis. Results Twenty ARGs were significantly associated with the overall survival of colon cancer patients. Five of these ARGs had a mutation rate ≥ 3%. Patients were divided into high-risk and low-risk groups based on Cox regression analysis of 8 ARGs. Low-risk patients had a significantly longer survival time than high-risk patients (p < 0.001). Univariate and multivariate Cox regression analysis showed that the resulting risk score, which was associated with infiltration depth and metastasis, could be an independent predictor of patient survival. A nomogram was established to predict 1-, 3-, and 5-year survival of colon cancer patients based on 5 independent prognosis factors, including the risk score. The prognostic nomogram with online webserver was more effective and convenient to provide information for researchers and clinicians. Conclusion The 8 ARGs can be used to predict the prognosis of patients and provide information for their individualized treatment.


2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Dan Chen ◽  
Xiaoting Li ◽  
Hui Li ◽  
Kai Wang ◽  
Xianghua Tian

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.


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