NFE2L3, also known as NFE2L3, is a nuclear transcription factor associated with the pathogenesis and progression of human tumors. To systematically and comprehensively investigate the role of NFE2L3 ...in tumors, a pan-cancer analysis was performed using multi-omics data, including gene expression analysis, diagnostic and prognostic analysis, epigenetic methylation analysis, gene alteration analysis, immune feature analysis, functional enrichment analysis, and tumor cell functional status analysis. Furthermore, the molecular mechanism of NFE2L3 in liver hepatocellular carcinoma (LIHC) was explored. The relationship between NFE2L3 expression and survival prognosis of patients with LIHC was analyzed and a nomogram prediction model was constructed. Our study showed that NFE2L3 expression was upregulated in most cancers, suggesting that NFE2L3 may play an important role in promoting cancer progression. NFE2L3 expression is closely related to DNA methylation, genetic alteration, immune signature, and tumor cell functional status in pan-cancers. Furthermore, NFE2L3 was demonstrated to be an independent risk factor for LIHC, and the nomogram model based on NFE2L3 expression had good prediction efficiency for the overall survival of patients with LIHC. In summary, our study indicated that NFE2L3 may be an important molecular biomarker for the diagnosis and prognosis of pan-cancer. NFE2L3 is expected to be a potential molecular target for the treatment of tumors.
Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of ...NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation
and
Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.
Aberrant expression of circRNAs is closely associated with the progression of gastric cancer; however, the specific mechanisms involved remain unclear. Our aim was to identify new gastric cancer ...biomarkers and explore the molecular mechanisms of gastric cancer progression. Therefore, we analyzed miRNA and circRNA microarrays of paired early-stage gastric cancer samples. Our study identified a new circRNA called hsa_circ_0069382, that had not been reported before and was expressed at low levels in gastric cancer tissues. Our study also included bioinformatics analyses which determined that the high expression of hsa_circ_0069382 regulated the BTG anti-proliferation factor 2 (BTG2)/ focal adhesion kinase (FAK) axis in gastric cancer lines by sponging for miR-15a-5p. Therefore, proliferation, invasion, and migration of gastric cancer is impacted. miR-15a-5p overexpression partially restored the effects of hsa_circ_0069382. This study provides potential new therapeutic options and a future direction to explore for gastric cancer treatment, and biomarkers.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Different matrisomal patterns are shared across carcinomas. However, little is known about whether there exists a unique tumor matrisome that modulates GC progression and immune ...regulation.
Methods
We conducted a genome-wide analysis based on matrisomal-related lncRNAs (MRLs) in 375 patients with GC from the Cancer Genome Atlas (TCGA) database. Patients were split into the training set and validation set at a ratio of 1:1 using the R package cart. Pearson correlation analysis (PCA) was performed to identify lncRNAs that correlated with matrisome based on differential expression genes. Subsequently, we performed univariate Cox regression analyses and lasso Cox analysis on these lncRNAs to construct a risk model. Considering the primary effect of GRASLND on the GC prognosis, we chose it for further validation in an experimental setting.
Results
We identified a 15-MRL signature to predict overall survival and immune cell infiltration of patients with GC. The AUC values to predict 5-year outcome in three sets were 0.89, 0.65, and 0.78, respectively. Further analyses suggested that the high-risk group showed more obvious immune cell infiltration, and demonstrated an immunologically “cold” profile.
In vitro
, knockdown of GRASLND could inhibit the invasion capability of GC cells, and downregulate the protein expression of crucial matrisomal-related gene MMP9.
Conclusions
The 15-MRL gene signature might serve as a relatively good predictive tool to manage patients with GC.
Previous studies revealed that both Helicobacter pylori infection and some cytokine gene polymorphisms are risk factors for gastric diseases. The association between H. pylori and gene polymorphisms ...is worth exploring. Here we conducted a case–control study and systematically evaluate on association between H. pylori infection and IL4, TNFA, and IL10 polymorphisms in a Chinese Han population in northwestern China, where gastric cancer is the major burden on the health and the leading cause of death in local community. The Sequenom MassArray platform was used to screen the genotypes and 14C-urea breath test was employed to determine H. pylori infection status of 705 participants of the local rural residents. Significant association between H. pylori infection and the IL4 rs34142320 polymorphism was observed in the dominant model (OR = 0.57, 95% CI = 0.40–0.80, P = 0.030). No significant association was found between IL4 rs2243250, TNFA rs1800630, TNFA rs1800629, TNFA rs1799964, IL10 rs1800871, IL10 rs1800896 and H. pylori infection. Haplotype analysis showed that T-DEL and G-C haplotypes of the observed IL4 SNPs were significantly associated with H. pylori infection. Our analysis demonstrated that the IL4 rs34142320 polymorphism has a protective effect on H. pylori infection in Chinese Han population.
Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known ...risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income,
(
) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy,
infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis.
eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.
Background:
Hepatocellular carcinoma (HCC) is one of the highly heterogeneous cancers that lacks an effective risk model for prognosis prediction. Therefore, we searched for angiogenesis-related ...immune genes that affected the prognosis of HCC to construct a risk model and studied the role of this model in HCC.
Methods:
In this study, we collected the transcriptome data of HCC from The
Cancer
Genome Atlas (TCGA) and the International
Cancer
Genome Consortium (ICGC) database. Pearson correlation analysis was performed to identify the association between immune genes and angiogenesis-related genes. Consensus clustering was applied to divide patients into clusters A and B. Subsequently, we studied the differentially expressed angiogenesis-related immune genes (DEari-genes) that affected the prognosis of HCC. The most significant features were identified by least absolute shrinkage and selection operator (LASSO) regression, and a risk model was constructed. The reliability of the risk model was evaluated in the TCGA discovery cohort and the ICGC validation cohort. In addition, we compared the novel risk model to the previous models based on ROC analysis. ssGSEA analysis was used for function evaluation, and pRRophetic was utilized to predict the sensitivity of administering chemotherapeutic agents.
Results:
Cluster A patients had favorable survival rates. A total of 23 DEari-genes were correlated with the prognosis of HCC. A five-gene (including BIRC5, KITLG, PGF, SPP1, and SHC1) signature-based risk model was constructed. After regrouping the HCC patients by the median score, we could effectively discriminate between them based on the adverse survival outcome, the unique tumor immune microenvironment, and low chemosensitivity.
Conclusion:
The five-gene signature-based risk score established by ari-genes showed a promising clinical prediction value.
Gastric cancer (GC) is one of the most common digestive tumors in Northwest China. Previous sequencing analysis revealed that family with sequence similarity 153 member B (FAM153B) might be the ...primary driver gene of GC. In this study, we aim to explore the potential roles of FAM153B in GC. Microarray data were firstly obtained from public databases with the aim to evaluate the genetic expression of FAM153B between GC and normal tissues. The results were verified in immunohistochemistry (IHC). We also performed the co-expression network analysis and enrichment analysis to identify underlying mechanisms. A correlation analysis of FAM153B expression and immune infiltration was performed then. Furthermore, two GC cell lines were used to evaluate the effect of FAM153B on gastric cell proliferation by employing MTT and Edu assays. Our findings suggest that FAM153B is downregulated in tumoral tissue, and positively associated with unfavorable survival. The enrichment pathways of FAM153B were regulation of signaling receptor activity, DNA replication, cell cycle transition, chromosomal regulation, and so on. Besides, from the perspective of bioinformatics, the protein expression level of FAM153B is related to the degree of immune cell infiltration. In vitro, overexpression of FAM153B inhibit the proliferation of two cell lines. In summary, this study demonstrates that FAM153B might serve as an effective prognostic and therapeutic biomarker in GC.
Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. The identification of valuable predictive signatures to improve the ...prognosis of patients with GC is becoming a realistic prospect. DNA damage response-related long noncoding ribonucleic acids (drlncRNAs) play an important role in the development of cancers. However, their prognostic and therapeutic values remain sparse in gastric cancer (GC).
We obtained the transcriptome data and clinical information from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort. Co-expression network analyses were performed to discover functional modules using the igaph package. Subsequently, lncRNA pairs were identified by bioinformation analysis, and prognostic pairs were determined by univariate analysis, respectively. In addition, we utilized least absolute shrinkage and selection operator (LASSO) cox regression analysis to construct the risk model based on lncRNA pairs. Then, we distinguished between the high- or low- risk groups from patients with GC based on the optimal model. Finally, we reevaluated the association between risk score and overall survival, tumor immune microenvironment, specific tumor-infiltrating immune cells related biomarkers, and the sensitivity of chemotherapeutic agents.
32 drlncRNA pairs were obtained, and a 17-drlncRNA pairs signature was constructed to predict the overall survival of patients with GC. The ROC was 0.797, 0.812 and 0.821 at 1, 2, 3 years, respectively. After reclassifying these patients into different risk-groups, we could differentiate between them based on negative overall survival outcome, specialized tumor immune infiltration status, higher expressed immune cell related biomarkers, and a lower chemotherapeutics sensitivity. Compared with previous models, our model showed better performance with a higher ROC value.
The prognostic and therapeutic signature established by novel lncRNA pairs could provide promising prediction value, and guide individual treatment strategies in the future.
Background
Esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer in the world with high incidence rate and poor prognosis. Infiltrated immune and stromal ...cells are vital components of tumor microenvironment (TME) and have a significant impact on the progression of ESCC. The competitive endogenous RNA (ceRNA) hypothesis has been proved important in the molecular biological mechanisms of tumor development. However, there are few studies on the relationship between ceRNA and ESCC TME.
Methods
The proportion of tumor-infiltrating immune cells and the amount of stromal and immune cells in ESCC cases were calculated from The Cancer Genome Atlas database using the CIBERSORT and ESTIMATE calculation methods. After stratified identification of differentially expressed genes, WGCNA and miRNA prediction system were applied to construct ceRNA network. Finally, PPI network and survival analysis were selected to discriminate prognostic signature. And the results were verified in two independent groups from Gene Expression Omnibus and Lanzhou, China.
Results
We found that high Stromal and ESTIMATE scores were significantly associated with poor overall survival. Three TME-related key prognostic genes were screened, namely, LCP2, CD86, SLA. And the expression of them was significantly correlated with infiltrated immunocytes. It is also found that ESTIMATE Score and the expression of CD86 were both related to TNM system of ESCC.
Conclusions
We identified three novel TME-related prognostic markers and their lncRNA-miRNA-mRNA pathway in ESCC patients, which may provide new strategies for the targeted therapy.
PDF
