Identification of 10 Gene Signatures as Prognostic Biomarkers for Peritoneal Metastatic Gastric Cancer

Author(s):  
Junliang Li ◽  
Lingfang Zhang ◽  
Tiankang Guo

Abstract Background. Peritoneal metastatic gastric cancer (PMGC) is very common, and usually, the prognosis is poor. There is currently an absence of accurate methods for the early diagnosis and prediction of peritoneal metastasis (PM). This highlights the need to develop strategies to identify the risk of PMGC. Methods. We performed a comprehensive discovery of biomarkers to predict PM by analyzing profiling datasets from GSE62254. The prognostic PM-related genes were obtained using the univariate Cox regression analysis, followed by a least absolute shrinkage and selection operator regression (LASSO) to establish a risk score model. The gene set enrichment analysis (GSEA) was used to determine the pathway enrichment in both the high- and low-risk groups. The 1-, 3-, and 5-year overall survival (OS) rates and area under the receiver operating characteristic curve (ROC) were used to compare the predictive accuracy-based risk stratification. In addition, an unsupervised clustering algorithm was applied to divide patients into subgroups according to the PM-related genes. Results. We identified 10 genes (MMP12, TAC1, TSPYL5, PPP1R14A, TMSB15B, NPY1R, PCDH9, EPM2AIP1, TIG7, and DYNC1I1) for PMGC diagnosis. The OS rates between the high- and low-risk groups at 1-, 3-, and 5-years were significantly different in the training and validation sets. The AUCs at 1-, 3-, and 5-years in the training set were 0.71, 0.74, and 0.73, respectively. In the validation set, the AUCs at 1-, 3-, and 5-years were 0.68, 0.66, and 0.69, respectively. The 10 gene signatures were correlated with immune cell infiltration in both the high- and low-risk groups. In addition, based on the GSEA, several significant pathways were enriched in the high-risk PMGC group, such as the Wnt and transforming growth factor beta (TGF-β) signaling pathway and leukocyte transendothelial migration pathway. Furthermore, unsupervised cluster analysis showed that the model could distinguish the level of risk among patients with PMGC. Conclusions. Overall, 10 gene signatures were identified for PMGC risk prediction. These may be valuable in making clinical decisions to improve treatment outcomes in patients with PMGC.

Author(s):  
Wei Jiang ◽  
Jiameng Xu ◽  
Zirui Liao ◽  
Guangbin Li ◽  
Chengpeng Zhang ◽  
...  

ObjectiveTo screen lung adenocarcinoma (LUAC)-specific cell-cycle-related genes (CCRGs) and develop a prognostic signature for patients with LUAC.MethodsThe GSE68465, GSE42127, and GSE30219 data sets were downloaded from the GEO database. Single-sample gene set enrichment analysis was used to calculate the cell cycle enrichment of each sample in GSE68465 to identify CCRGs in LUAC. The differential CCRGs compared with LUAC data from The Cancer Genome Atlas were determined. The genetic data from GSE68465 were divided into an internal training group and a test group at a ratio of 1:1, and GSE42127 and GSE30219 were defined as external test groups. In addition, we combined LASSO (least absolute shrinkage and selection operator) and Cox regression analysis with the clinical information of the internal training group to construct a CCRG risk scoring model. Samples were divided into high- and low-risk groups according to the resulting risk values, and internal and external test sets were used to prove the validity of the signature. A nomogram evaluation model was used to predict prognosis. The CPTAC and HPA databases were chosen to verify the protein expression of CCRGs.ResultsWe identified 10 LUAC-specific CCRGs (PKMYT1, ETF1, ECT2, BUB1B, RECQL4, TFRC, COCH, TUBB2B, PITX1, and CDC6) and constructed a model using the internal training group. Based on this model, LUAC patients were divided into high- and low-risk groups for further validation. Time-dependent receiver operating characteristic and Cox regression analyses suggested that the signature could precisely predict the prognosis of LUAC patients. Results obtained with CPTAC, HPA, and IHC supported significant dysregulation of these CCRGs in LUAC tissues.ConclusionThis prognostic prediction signature based on CCRGs could help to evaluate the prognosis of LUAC patients. The 10 LUAC-specific CCRGs could be used as prognostic markers of LUAC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kebing Huang ◽  
Xiaoyu Yue ◽  
Yinfei Zheng ◽  
Zhengwei Zhang ◽  
Meng Cheng ◽  
...  

Glioma is well known as the most aggressive and prevalent primary malignant tumor in the central nervous system. Molecular subtypes and prognosis biomarkers remain a promising research area of gliomas. Notably, the aberrant expression of mesenchymal (MES) subtype related long non-coding RNAs (lncRNAs) is significantly associated with the prognosis of glioma patients. In this study, MES-related genes were obtained from The Cancer Genome Atlas (TCGA) and the Ivy Glioblastoma Atlas Project (Ivy GAP) data sets of glioma, and MES-related lncRNAs were acquired by performing co-expression analysis of these genes. Next, Cox regression analysis was used to establish a prognostic model, that integrated ten MES-related lncRNAs. Glioma patients in TCGA were divided into high-risk and low-risk groups based on the median risk score; compared with the low-risk groups, patients in the high-risk group had shorter survival times. Additionally, we measured the specificity and sensitivity of our model with the ROC curve. Univariate and multivariate Cox analyses showed that the prognostic model was an independent prognostic factor for glioma. To verify the predictive power of these candidate lncRNAs, the corresponding RNA-seq data were downloaded from the Chinese Glioma Genome Atlas (CGGA), and similar results were obtained. Next, we performed the immune cell infiltration profile of patients between two risk groups, and gene set enrichment analysis (GSEA) was performed to detect functional annotation. Finally, the protective factors DGCR10 and HAR1B, and risk factor SNHG18 were selected for functional verification. Knockdown of DGCR10 and HAR1B promoted, whereas knockdown of SNHG18 inhibited the migration and invasion of gliomas. Collectively, we successfully constructed a prognostic model based on a ten MES-related lncRNAs signature, which provides a novel target for predicting the prognosis for glioma patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xiaotao Jiang ◽  
Qiaofeng Yan ◽  
Linling Xie ◽  
Shijie Xu ◽  
Kailin Jiang ◽  
...  

Background. Gastric cancer (GC), an extremely aggressive tumor with a very different prognosis, is the third leading cause of cancer-related mortality. We aimed to construct a ferroptosis-related prognostic model that can be distinguished prognostically. Methods. The gene expression and the clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). The ferroptosis-related genes were obtained from the FerrDb. Using the “limma” R package and univariate Cox analysis, ferroptosis-related genes with differential expression and prognostic value were identified in the TCGA cohort. Last absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink ferroptosis-related predictors and construct a prognostic model. Functional enrichment, ESTIMATE algorithm, and single-sample gene set enrichment analysis (ssGSEA) were applied for exploring the potential mechanism. GC patients from the GEO cohort were used for validation. Results. An 8-gene prognostic model was constructed and stratified GC patients from TCGA and meta-GEO cohort into high-risk groups or low-risk groups. GC patients in high-risk groups have significantly poorer OS compared with those in low-risk groups. The risk score was identified as an independent predictor for OS. Functional analysis revealed that the risk score was mainly associated with the biological function of extracellular matrix (ECM) organization and tumor immunity. Conclusion. In conclusion, the ferroptosis-related model can be utilized for the clinical prognostic prediction in GC.


2021 ◽  
Author(s):  
Zhehong Li ◽  
Junqiang Wei ◽  
Honghong Zheng ◽  
Xintian Gan ◽  
Mingze Song ◽  
...  

Abstract Background: Hypoxia- and immune-status play an essential role in tumorigenesis and tumor development. This study sought to build a novel hypoxia- and immune-related signature to evaluate sarcoma patients' prognosis.Methods: Transcriptome data and clinicopathological characteristics of sarcoma patients were downloaded from the TARGET database. We grouped patients with three clusters by using t-SNE. We defined the three cluster as high-, medium-, and low-hypoxia clusters by K-M analysis and differential expression of target genes associated with the HIF-1 signaling pathway. Then we used the "limma" package to screen hypoxia-related differentially expressed genes (HRDEGs) in the high- and low-hypoxia clusters. We immediately assessed the immune status by using the single sample Gene Set Enrichment Analysis (ssGSEA) and divided the patients into high-, medium-, and low-immune clusters. Immune-related DEGs (IRDEGs) were filtered in the high- and low- immune groups. The intersection of HRDEGs and IRDEGs screened overlapping genes. We used a combination of Cox regression analysis and LASSO model to obtain prognosis-related genes and established a novel hypoxia- and immune-related prognostic signature for sarcoma patients. Combining clinicopathological characteristics of sarcoma patients, we evaluated the signature by univariate and multivariate Cox regression analysis. We further divided the patients into high- and low-risk groups based on the novel signature. Finally, we evaluated the differences in hypoxia status and the immune status in high- and low-risk groups.Results: We identified two genes associated with prognosis, CMA1 and IGDCC3. The novel Prognostic signature could be used as an independent prognostic factor for sarcoma patients. We distinguished patients more effectively by their different survival outcomes, immune cells' infiltration status, and immune-related markers.Conclusion: The hypoxia- and immune-related prognostic signature can be used to stratify the risk of sarcoma patients. Our study established a new prognostic signature and provides a potential prognostic markers for hypoxia- and immune-related therapy.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Renshen Xiang ◽  
Wei Song ◽  
Jun Ren ◽  
Jing Wu ◽  
Jincheng Fu ◽  
...  

Abstract Background Although numerous studies demonstrate the role of cancer stem cells in occurrence, recurrence, and distant metastases in gastric cancer (GC), little is known about the evolving genetic and epigenetic changes in the stem and progenitor cells. The purpose of this study was to identify the stem cell subtypes in GC and examine their clinical relevance. Methods Two publicly available datasets were used to identify GC stem cell subtypes, and consensus clustering was performed by unsupervised machine learning methods. The cancer stem cell (CSC) typing-related risk scoring (RS) model was established through multivariate Cox regression analysis. Results Cross-platform dataset-based two stable GC stem cell subtypes, namely low stem cell enrichment (SCE_L) and high stem cell enrichment (SCE_H), were prudently identified. Gene set enrichment analysis revealed that the classical oncogenic pathways, immune-related pathways, and regulation of stem cell division were active in SCE_H; ferroptosis, NK cell activation, and post-mutation repair pathways were active in SCE_L. GC stem cell subtypes could accurately predict clinical outcomes in patients, tumor microenvironment cell-infiltration characteristics, somatic mutation landscape, and potential responses to immunotherapy, targeted therapy, and chemotherapy. Additionally, a CSC typing-related RS model was established; it was strongly independent and could accurately predict the patient’s overall survival. Conclusions This study demonstrated the complex oncogenic mechanisms underlying GC. The findings provide a basis and reference for the diagnosis and treatment of GC.


Author(s):  
Bo Xiao ◽  
Liyan Liu ◽  
Zhuoyuan Chen ◽  
Aoyu Li ◽  
Pingxiao Wang ◽  
...  

Melanoma is the most common cancer of the skin, associated with a worse prognosis and distant metastasis. Epithelial–mesenchymal transition (EMT) is a reversible cellular biological process that plays significant roles in diverse tumor functions, and it is modulated by specific genes and transcription factors. The relevance of EMT-related lncRNAs in melanoma has not been determined. Therefore, RNA expression data and clinical features were collected from the TCGA database (N = 447). Melanoma samples were randomly assigned into the training (315) and testing sets (132). An EMT-related lncRNA signature was constructed via comprehensive analyses of lncRNA expression level and corresponding clinical data. The Kaplan-Meier analysis showed significant differences in overall survival in patients with melanoma in the low and high-risk groups in two sets. Receiver operating characteristic (ROC) curves were used to measure the performance of the model. Cox regression analysis indicated that the risk score was an independent prognostic factor in two sets. Besides, a nomogram was constructed based on the independent variables. Gene Set Enrichment Analysis (GSEA) was applied to evaluate the potential biological functions in the two risk groups. Furthermore, the melanoma microenvironment was evaluated using ESTIMATE and CIBERSORT algorithms in the risk groups. This study indicates that EMT-related lncRNAs can function as potential independent prognostic biomarkers for melanoma survival.


2021 ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Yuhua Zheng ◽  
Xiaochun Liu

Abstract Background: Cervical cancer (CC) is one of the most common malignancies in gynecology. There is still a lack of specific biomarkers for the diagnosis and prognosis of CC. Pyroptosis is one of the methods of programmed cell death, and its various components are related to the occurrence, invasion, and metastasis of tumors. However, the role of pyroptosis in CC has not yet been elucidated.Methods: This study focuses on the development of a prognostic signature associated with pyroptosis for CC patients using integrated bioinformatics to elucidate the relationship between the signature and the tumor microenvironment and immune response.Results: We identified a prognostic signature based on eight pyroptosis-related genes (PRGs), with better prognostic survival in the low-risk group (P<0.05) and AUC values greater than 0.7. The results of the multi-factor Cox regression analysis indicated that the signature could be used as an independent prognostic factor, and both the DCA and the Nomogram suggested that the prognostic signature had good predictive power. Interestingly, this prognostic signature can also be applied to multiple tumors. In addition, the tumor microenvironment and immune infiltration status were significantly different between high and low-risk groups (P<0. 05). The core gene GZMB was screened and the CC-associated GZMB/ miR-378a/TRIM52-AS1 regulatory axis was constructed.Conclusion: The study successfully established the prognostic signature based on eight PRGs and reflected their tumor microenvironment and immune infiltration. The GZMB/ miR-378a/TRIM52-AS1 regulatory axis may play an important regulatory role in the development of CC, and further experimental studies are needed to validate these results subsequently.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pu Wu ◽  
Jinyuan Shi ◽  
Wei Sun ◽  
Hao Zhang

Abstract Background Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear. Objective This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival. Methods A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort. Results A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues. Conclusion In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoping Li ◽  
Jishang Chen ◽  
Qihe Yu ◽  
Hui Huang ◽  
Zhuangsheng Liu ◽  
...  

Background: A surge in newly diagnosed breast cancer has overwhelmed the public health system worldwide. Joint effort had beed made to discover the genetic mechanism of these disease globally. Accumulated research has revealed autophagy may act as a vital part in the pathogenesis of breast cancer.Objective: Aim to construct a prognostic model based on autophagy-related lncRNAs and investigate their potential mechanisms in breast cancer.Methods: The transcriptome data and clinical information of patients with breast cancer were obtained from The Cancer Genome Atlas (TCGA) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). Long non-coding RNAs (lncRNAs) related to autophagy were acquired through the Pearson correlation analysis. Univariate Cox regression analysis as well as the least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify autophagy-related lncRNAs with prognostic value. We constructed a risk scoring model to assess the prognostic significance of the autophagy-related lncRNAs signatures. The nomogram was then established based on the risk score and clinical indicators. Through the calibration curve, the concordance index (C-index) and receiver operating characteristic (ROC) curve analysis were evaluated to obtain the model's predictive performance. Subgroup analysis was performed to evaluate the differential ability of the model. Subsequently, gene set enrichment analysis was conducted to investigate the potential functions of these lncRNAs.Results: We attained 1,164 breast cancer samples from the TCGA database and 231 autophagy-related genes from the HAD database. Through correlation analysis, 179 autophagy-related lncRNAs were finally identified. Univariate Cox regression analysis and LASSO regression analysis further screened 18 prognosis-associated lncRNAs. The risk scoring model was constructed to divide patients into high-risk and low-risk groups. It was found that the low-risk group had better overall survival (OS) than those of the high-risk group. Then, the nomogram model including age, tumor stage, TNM stage and risk score was established. The evaluation index (C-index: 0.78, 3-year OS AUC: 0.813 and 5-year OS AUC: 0.785) showed that the nomogram had excellent predictive power. Subgroup analysis showed there were difference in OS between high-risk and low-risk patients in different subgroups (stage I-II, ER positive, Her-2 negative and non-TNBC subgroups; all P &lt; 0.05). According to the results of gene set enrichment analysis, these lncRNAs were involved in the regulation of multicellular organismal macromolecule metabolic process in multicellular organisms, nucleotide excision repair, oxidative phosphorylation, and TGF-β signaling pathway.Conclusions: We identified 18 autophagy-related lncRNAs with prognostic value in breast cancer, which may regulate tumor growth and progression in multiple ways.


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