Comprehensive Analysis of Gene Expression Profiles Identifies a<i>P4HA1</i>-Related Gene Panel as a Prognostic Model in Colorectal Cancer Patients

Chen, Zhangxin; Chen, Mei-Yan; Xue, Zengyan; Zhu, Xiaoyan

doi:10.1089/cbr.2021.0242

Cited by 4 publications

(4 citation statements)

References 26 publications

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“…While the specific mechanisms in COAD remain unclear, NXPH4 likely cooperates with these metabolic pathways to facilitate energy generation and oxygen adaptation. These results are consistent with previously reported studies ( 52 - 54 ), and targeting NXPH4-associated glycolysis and hypoxia response genes could offer new therapeutic approaches to disrupt the bioenergetics and stress tolerance pathways critical for colon cancer progression.…”

Section: Discussionsupporting

confidence: 93%

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

Sun,

Wang,

et al. 2024

J Gastrointest Oncol

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Background Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although neurexophilin 4 (NXPH4) has been investigated in several tumors, its role in COAD remains unclear. The aim of this study was to explore the prognostic value and potential functions of NXPH4 in COAD. Methods The expression of NXPH4 in COAD were analyzed using The Cancer Genome Atlas (TCGA) and datasets from the Gene Expression Omnibus (GEO) database. The prognostic value of NXPH4 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NXPH4 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NXPH4 expression and immune cell infiltration levels was examined thorough single-sample gene set enrichment analysis (ssGSEA). Furthermore, the competing endogenous RNA (ceRNA) regulatory network that may be involved in NXPH4 in COAD was predicted and constructed through a variety of databases. Results NXPH4 expression was significantly higher in COAD tissue compared with normal colon tissues. Meanwhile, high expression of NXPH4 was associated with poor prognosis in COAD patients. GO-KEGG and GSEA analyses indicated that NXPH4 was associated with glycolysis and hypoxia pathway, and may promote COAD progression and metastasis by modulating metabolic reprogramming. ssGSEA analysis demonstrated that NXPH4 expression also associated with immune infiltration. Furthermore, we identified various microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) as upstream regulators of NXPH4 in COAD. Conclusions The present study revealed that high expression of NXPH4 is associated with tumor progression, metabolic reprogramming, and immune infiltration. These findings suggest that NXPH4 could serve as a reliable prognostic biomarker and a promising therapeutic target in COAD.

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Section: Discussionsupporting

confidence: 93%

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

Sun,

Wang,

et al. 2024

J Gastrointest Oncol

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“…Among these genes, we noticed that C5ORF46 was approximately 64-fold differentially expressed (log2FC = 6.18, p = 0.00071), which presented as the most differentially expressed one. Similarly, previous studies suggested a pro-tumoral and prognostic role of C5ORF46 in several GI tumors, including PAAD (Makler and Narayanan, 2017), COAD (Chen et al, 2021), and STAD (Cheng et al, 2020). We postulated that C5ORF46 may be a potential prognostic marker for human GI tumors.…”

Section: Identification Of C5orf46supporting

confidence: 74%

“…They found C5ORF46 was related to poor prognosis in recurrent GBM (rGBM) patients (Tang et al, 2021). Similarly, by analyzing the TCGA expression profile, C5ORF46 was found to be differentially expressed and have prognostic significance in the context of stomach cancer (Cheng et al, 2020) and colorectal cancer (Chen et al, 2021). Further, the potential of exosomal C5ORF46 as a tumor marker in pancreatic cancer was uncovered by bioinformatics analyses using multiple ORF databases (Makler and Narayanan, 2017).…”

Section: Discussionmentioning

confidence: 98%

“…A recent study detected C5ORF46 in human plasma and revealed C5ORF46 to be a previously-uncharacterized small human plasma protein that may be associated with lipid homeostasis (Harney et al, 2019). Several reports implicate C5ORF46 as having a pro-tumoral role with possible prognostic value in the development of pancreatic adenocarcinoma (PAAD) (Makler and Narayanan, 2017), colon adenocarcinoma (COAD) (Chen et al, 2021) and stomach adenocarcinoma (STAD) (Cheng et al, 2020), which underline the value of studying C5ORF46 in GI tumors (Makler and Narayanan, 2017;Cheng et al, 2020). However, with limited evidence, the role of C5ORF46 in cancer development remains unexplained.…”

Section: Introductionmentioning

confidence: 99%

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A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker

Jiang

Wang²,

Li³

et al. 2022

Front. Genet.

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Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.

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Identification of a novel Immune-Related prognostic model for patients with colorectal cancer based on 3 subtypes

Yang

Wei

2023

Immunobiology

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Comprehensive Analysis of Gene Expression Profiles Identifies aP4HA1-Related Gene Panel as a Prognostic Model in Colorectal Cancer Patients

Cited by 4 publications

References 26 publications

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

A systematic analysis of C5ORF46 in gastrointestinal tumors as a potential prognostic and immunological biomarker

Identification of a novel Immune-Related prognostic model for patients with colorectal cancer based on 3 subtypes

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