Identification of GGT5 as a Novel Prognostic Biomarker for Gastric Cancer and its Correlation With Immune Cell Infiltration

Wang, Yuli; Fang, Yuan; Zhao, Fanchen; Gu, Jiefei; Lv, Xiang; Zhang, Bo; Fang, Zhihong; Li, Yan

doi:10.3389/fgene.2022.810292

Cited by 12 publications

(9 citation statements)

References 53 publications

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“…GGT5, the protein with the strongest correlation with the BEP score, is highly expressed in macrophages and its tissue expression correlates with macrophage infiltration. 52 Cluster of differentiation 14 (CD14), an important macrophage surface marker, is also elevated in MC2 endplate‐near bone marrow. Therefore, our data point at increased numbers of macrophages in MC2.…”

Section: Discussionmentioning

confidence: 99%

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

et al. 2022

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Background Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. Aims The aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration. Methods Pairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. Results Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. Discussion The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate-near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. Conclusion MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates.

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Section: Discussionmentioning

confidence: 99%

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

et al. 2022

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“…GGT5 (Gamma-Glutamyltransferase 5) is a member of the gamma-glutamyl transpeptidase gene family involved in glutathione metabolism ( Wickham et al, 2011 ). GGT5 was associated with immune cell infiltration and might be a potential immunological therapeutic target in gastric cancer ( Wang et al, 2022 ). ASAH1 (N-Acylsphingosine Amidohydrolase 1) encodes a member of the acid ceramidase family of proteins and is involved in glycosphingolipid metabolism ( Li et al, 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel lipid metabolism-related gene signature for predicting colorectal cancer survival

et al. 2022

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Colorectal cancer (CRC) is a common malignant tumor worldwide. Lipid metabolism is a prerequisite for the growth, proliferation and invasion of cancer cells. However, the lipid metabolism-related gene signature and its underlying molecular mechanisms remain unclear. The aim of this study was to establish a lipid metabolism signature risk model for survival prediction in CRC and to investigate the effect of gene signature on the immune microenvironment. Lipid metabolism-mediated genes (LMGs) were obtained from the Molecular Signatures Database. The consensus molecular subtypes were established using “ConsensusClusterPlus” based on LMGs and the cancer genome atlas (TCGA) data. The risk model was established using univariate and multivariate Cox regression with TCGA database and independently validated in the international cancer genome consortium (ICGC) datasets. Immune infiltration in the risk model was developed using CIBERSORT and xCell analyses. A total of 267 differentially expressed genes (DEGs) were identified between subtype 1 and subtype 2 from consensus molecular subtypes, including 153 upregulated DEGs and 114 downregulated DEGs. 21 DEGs associated with overall survival (OS) were selected using univariate Cox regression analysis. Furthermore, a prognostic risk model was constructed using the risk coefficients and gene expression of eleven-gene signature. Patients with a high-risk score had poorer OS compared with patients in the low-risk score group (p = 3.36e-07) in the TCGA cohort and the validationdatasets (p = 4.03e-05). Analysis of immune infiltration identified multiple T cells were associated with better prognosis in the low-risk group, including Th2 cells (p = 0.0208), regulatory T cells (p = 0.0425), and gammadelta T cells (p = 0.0112). A nomogram integrating the risk model and clinical characteristics was further developed to predict the prognosis of patients with CRC. In conclusion, our study revealed that the expression of lipid-metabolism genes were correlated with the immune microenvironment. The eleven-gene signature might be useful for prediction the prognosis of CRC patients.

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“…Numerous studies have found that different types of immune cells infiltrate tumors in large numbers and that their distribution, tissue location, and cell type are all linked to tumor development and survival ( 17 ). We found that the expression levels of FCN2 are abnormally low in HCC.…”

Section: Discussionmentioning

confidence: 99%

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

Wang

Zeng²,

Jiang³

et al. 2022

Front. Oncol.

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ObjectiveThis study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.MethodsOncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.ResultsIn HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.ConclusionFCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

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Identification of GGT5 as a Novel Prognostic Biomarker for Gastric Cancer and its Correlation With Immune Cell Infiltration

Cited by 12 publications

References 53 publications

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates

Identification of a novel lipid metabolism-related gene signature for predicting colorectal cancer survival

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

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