Dataset Information

Iroquois Family Genes in Gastric Carcinogenesis: A Comprehensive Review.

ABSTRACT: Gastric cancer (GC) is the fifth leading cause of cancer-associated death worldwide, accounting for 768,793 related deaths and 1,089,103 new cases in 2020. Despite diagnostic advances, GC is often detected in late stages. Through a systematic literature search, this study focuses on the associations between the Iroquois gene family and GC. Accumulating evidence indicates that Iroquois genes are involved in the regulation of various physiological and pathological processes, including cancer. To date, information about Iroquois genes in GC is very limited. In recent years, the expression and function of Iroquois genes examined in different models have suggested that they play important roles in cell and cancer biology, since they were identified to be related to important signaling pathways, such as wingless, hedgehog, mitogen-activated proteins, fibroblast growth factor, TGFβ, and the PI3K/Akt and NF-kB pathways. In cancer, depending on the tumor, Iroquois genes can act as oncogenes or tumor suppressor genes. However, in GC, they seem to mostly act as tumor suppressor genes and can be regulated by several mechanisms, including methylation, microRNAs and important GC-related pathogens. In this review, we provide an up-to-date review of the current knowledge regarding Iroquois family genes in GC.

SUBMITTER: Dos Santos EC

PROVIDER: S-EPMC10048635 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Iroquois Family Genes in Gastric Carcinogenesis: A Comprehensive Review.

Dos Santos Everton Cruz EC Petrone Igor I Binato Renata R Abdelhay Eliana E

Genes 20230301 3

Gastric cancer (GC) is the fifth leading cause of cancer-associated death worldwide, accounting for 768,793 related deaths and 1,089,103 new cases in 2020. Despite diagnostic advances, GC is often detected in late stages. Through a systematic literature search, this study focuses on the associations between the Iroquois gene family and GC. Accumulating evidence indicates that Iroquois genes are involved in the regulation of various physiological and pathological processes, including cancer. To d ...[more]

PMID: 36980893

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Project description:Gastric cancer, a prevalent malignancy, often presents challenges due to its low early diagnosis rate and poor prognosis. This study aims to establish a prognostic model composed of genes from the CLEC family, aiming to predict the prognosis of gastric cancer patients effectively. Data Collection: mRNA expression matrices and clinical data were downloaded from the TCGA, GEO, and GTEx databases. Differential analysis, univariate Cox analysis, lasso regression analysis, and multivariate Cox analysis were conducted to identify three genes associated with the prognosis of the CLEC family for building a prognostic model. Prognostic Model Construction: A prognostic model comprising these three genes was constructed. The prognostic value was evaluated using Kaplan-Meier plots, time-dependent receiver operating characteristic curves, multivariable Cox regression analysis incorporating clinical information, and a nomogram. The predictive value of the three-gene signature was further validated using the GSE84437 dataset. Immune and Functional Analyses: Differences in immune status and signaling pathways between different risk groups were assessed through analyses of the tumor microenvironment, immune cell infiltration, immune function, and gene set enrichment. Through tumor mutation analysis, the molecular mechanisms of tumors were revealed. Finally, chemotherapy-sensitivity drugs were identified through drug analysis. Results revealed CD93, CLEC3A, and VCAN as three CLEC family genes associated with prognosis. Multivariable Cox regression analysis demonstrated that these three CLEC family genes were independent prognostic factors for overall survival in gastric cancer patients. Additionally, we constructed a prognostic nomogram that incorporated risk score, age, grade, and stage. Based on TCGA/GSE84437 data, calibration plots demonstrated its predictive solid performance. Furthermore, immune-related analyses and drug sensitivity assessments suggested a close association between the three-gene model and immune cell infiltration, indicating their potential as predictive indicators for chemotherapy sensitivity. We have identified a CLEC family gene model consisting of three genes associated with the prognosis of gastric cancer. This provides a basis for personalized prevention and treatment strategies.

Project description:The solute carrier 30 (SLC30) family genes play a fundamental role in various cancers. However, the diverse expression patterns, prognostic value, and potential mechanism of SLC30A family genes in gastric cancer (GC) remain unknown. Herein, we analyzed the expression and survival data of SLC30A family genes in GC patients using multiple bioinformatic approaches. Expression data of SLC30A family genes for GC patients were extracted from the Cancer Genome Atlas (TCGA) and genetic alteration frequency assessed by using cBioportal database. And validated the expression of SLC30A family genes in GC tissues and corresponding normal tissues. The prognostic value of SLC30A family genes in gastric cancer patients were explored using Kaplan-Meier plotter database. Functional enrichment analysis performed using DAVID database and clusterProfiler package. And ssGSEA algorithm was performed to explore the relationship between the SLC30A family genes and the infiltration of immune cells. We found that the median expression levels of SLC30A1-3, 5-7, and 9 were significantly upregulated in gastric cancer tissues compared to non-cancerous tissues, while SLC30A4 was downregulated. Meanwhile, SLC30A1-7, and 9 were significantly correlated with advanced tumor stage and nodal metastasis status, SLC30A5-7, and 9-10 were significantly related to the Helicobacter pylori infection status of GC patients. High expression of five genes (SLC30A1, 5-7, and 9) was significantly correlated with better overall survival (OS), first progression survival (FPS), and post progression survival (PPS). Conversely, upregulated SLC30A2-4, 8, and 10 expression was markedly associated with poor OS, FP and PPS. And SLC30A family genes were closely associated with the infiltration of immune cells. The present study implied that SLC30A5 and 7 may be potential biomarkers for predicting prognosis in GC patients, SLC30A2 and 3 play an oncogenic role in GC patients and could provide a new strategy for GC patients treatment.

Project description:BackgroundThe iroquois (iro/Irx) genes encode transcriptional regulators that belong to the TALE superclass of homeodomain proteins and have key functions during development in both vertebrates and insects. The Irx genes occur in one or two genomic clusters containing three genes each within the Drosophila and several vertebrate genomes, respectively. The similar genomic organization in Drosophila and vertebrates is widely considered as a result of convergent evolution, due to independent tandem gene duplications. In this study, we investigate the evolutionary history of the Irx genes at the scale of the whole metazoan kingdom.ResultsWe identified in silico the putative full complement of Irx genes in the sequenced genomes of 36 different species representative of the main metazoan lineages, including non bilaterian species, several arthropods, non vertebrate chordates, and a basal vertebrate, the sea lamprey. We performed extensive phylogenetic analyses of the identified Irx genes and defined their genomic organizations. We found that, in most species, there are several Irx genes, these genes form two to four gene clusters, and the Irx genes are physically linked to a structurally and functionally unrelated gene known as CG10632 in Drosophila.ConclusionThree main conclusions can be drawn from our study. First, an Irx cluster composed of two genes, araucan/caupolican and mirror, is ancestral to the crustaceans+insects clade and has been strongly conserved in this clade. Second, three Irx genes were probably present in the last common ancestor of vertebrates and the duplication that has given rise to the six genes organized into two clusters found in most vertebrates, likely occurred in the gnathostome lineage after its separation from sea lampreys. Third, the clustered organization of the Irx genes in various evolutionary lineages may represent an exceptional case of convergent evolution or may point to the existence of an Irx gene cluster ancestral to bilaterians.

Dataset Information

Iroquois Family Genes in Gastric Carcinogenesis: A Comprehensive Review.

Publications

Iroquois Family Genes in Gastric Carcinogenesis: A Comprehensive Review.

Similar Datasets

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