Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients

Wang, Junyou; Tong, Luqing; Lin, Gaojun; Wang, Hui; Zhang, Liang; Yang, Xuejun

doi:10.1186/s12885-020-07436-6

Cited by 6 publications

(6 citation statements)

References 37 publications

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“…Among the DEPs, the protein products of the genes C1RL, NID1, FN1, and PCYOX were upregulated in NT1. C1RL was previously found to be involved in immunological activities and reported as an independent prognostic biomarker in glioblastoma (GBM); interestingly, C1RL was also found to be upregulated (in GBM) in the study [ 40 , 41 ]. FN1 is a gene commonly reported in gene expression studies related to cancer and neurodegenerative diseases [ 19 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 92%

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

et al. 2023

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Narcolepsy type 1 (NT1) is the most common type of narcolepsy known to be caused by the loss of specific neurons responsible for producing peptide neurotransmitters (orexins/hypocretins), resulting in a sleep-wake cycle disorder. It is characterized by its association with cataplexy and abnormalities in rapid eye movement. To date, no cure has been established for this life-threatening condition. Misdiagnosis of NT1 is also quite common, although it is not exceedingly rare. Therefore, successfully identifying candidate serum biomarkers for NT1 would be a head start for accurate diagnosis and development of therapeutics for this disorder. This study aims to identify such potential serum biomarkers. A depletion protocol was employed for 27 human serum samples (16 NT1 and 11 healthy controls), followed by applying LC-MS/MS bottom-up proteomics analysis, then LC-PRM-MS for validation. The comparison of the proteome profiles of the low-abundant proteins in the samples was then investigated based on age, sex, sample groups, and the presence of the Human Leukocyte Antigen (HLA) DQB1*0602 allele. The results were tracked to gene expression studies as well as system biology to identify key proteins and understand their relationship in the pathogenesis of NT1. Our results revealed 36 proteins significantly and differentially expressed. Among the impaired pathways and bioprocesses, the complement activation pathway is impaired by six of the differentially expressed proteins (DEPs). They are coded by the genes C2, CFB, C5, C1R, C1S, and MASP1, while 11 DEPs are involved in Acute Phase Response Signaling (APRS), which are coded by the genes FN1, AMBP, APOH, CFB, CP, ITIH2, C5, C2, F2, C1, and ITIH4. The combined AUCs of the downregulated and upregulated DEPs are 0.95 and 0.76, respectively. Overall, this study reveals potential serum-protein biomarkers of NT1 and explains the possible correlation between the biomarkers and pathophysiological effects, as well as important biochemical pathways involved in NT1.

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Section: Discussionmentioning

confidence: 92%

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

et al. 2023

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“…A study found higher levels of C1Q expression were correlated with unfavorable prognosis in LGG ( 63 ). Other studies suggested that C3 and C1RL can serve as diagnostic biomarkers and potential targets of therapy for LGG patients ( 78 , 79 ). On the other hand, TF is related to epithelial-mesenchymal transition (EMT) and has the potential to become an effective target against EMT and thrombotic events in LGG.…”

Section: Discussionmentioning

confidence: 99%

Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma

Yang,

Shen,

Yang

et al. 2024

Transl Cancer Res

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Background Abnormal coagulation is a common feature of glioma. There is a strong correlation between coagulation and the complement system, named complement and coagulation cascades (CCC). However, the role of CCC genes in lower-grade glioma (LGG) remains unclear. This study aimed to investigate the role of CCC genes in LGG. Methods In total, 5,628 differential expressed genes were identified between 498 LGG tissues from The Cancer Genome Atlas (TCGA) and 207 normal brain tissues from Genotype-Tissue Expression Project (GTEx). Among them, 20 overlapped CCC genes were identified as differentially expressed CCC genes. Then, comprehensive bioinformatics analysis was used to investigate the role of CCC genes in LGG; 271 LGG tissues from the Chinese Glioma Genome Atlas (CGGA) were used as the validation dataset. Cell Counting Kit-8 (CCK8) proliferation assay, colony formation assay, and wound healing assay were conducted to explore the anti-glioma effect of the sensitive drugs we predicted. Results We constructed a risk signature consisting of six CCC genes, including F2R , SERPINA1 , TFPI , C1QC , C2 , and C3AR1 . The CCC gene-based risk signature could accurately predict the prognosis of patients with LGG. In addition, we found that the JAK-STAT, NOD-like receptor, Notch, PI3K-Akt, and Rap1 signaling pathways might be activated and had crosstalk with CCC in the high-risk group. Our findings analyses demonstrated that samples in high- and low-risk groups had different immune landscapes. Moreover, patients in the high-risk group might have greater resistance to immunotherapy. We validated the accuracy of the risk signature in predicting immunotherapy response in two public immunotherapy cohorts, GSE135222 and GSE78220. By means of oncoPredict, MG-132, BMS-536924, PLX-4720, and AZD6482 were identified as potential sensitive drugs for high-risk patients, of which MG-132 was particularly recommended for high-risk patients. We performed in vitro experiments to explore the anti-glioma effect of MG-132, and the results demonstrated MG-132 could inhibit the proliferation and migration of glioma cells. Conclusions Our findings show that CCC genes are associated with the prognosis and immune infiltration of LGG and provide possible immunotherapeutic and novel chemotherapeutic strategies for patients with LGG based on the risk signature.

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“…The p values of significant glycopeptides are shown in Table 2. The protein sources of significant glycopeptides were already reportedly involved in immunological activities, cancer, and neurodegenerative disease [43,55]. Inter-alpha-trypsin inhibitor H4, complement factor B, ceruloplasmin, fibronectin, and prothrombin were among the significant glycoproteins that were identified in the 28 significant glycopeptides.…”

Section: Discussionmentioning

confidence: 99%

LC-MS/MS Quantitation of HILIC-Enriched N-glycopeptides Derived from Low-Abundance Serum Glycoproteins in Patients with Narcolepsy Type 1

Atashi,

Reyes,

Sandilya

et al. 2023

Biomolecules

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Glycoproteomic analysis is always challenging because of low abundance and complex site-specific heterogeneity. Glycoproteins are involved in various biological processes such as cell signaling, adhesion, and cell–cell communication and may serve as potential biomarkers when analyzing different diseases. Here, we investigate glycoproteins in narcolepsy type 1 (NT1) disease, a form of narcolepsy characterized by cataplexy—the sudden onset of muscle paralysis that is typically triggered by intense emotions. In this study, 27 human blood serum samples were analyzed, 16 from NT1 patients and 11 from healthy individuals serving as controls. We quantified hydrophilic interaction liquid chromatography (HILIC)-enriched glycopeptides from low-abundance serum samples of controls and NT1 patients via LC-MS/MS. Twenty-eight unique N-glycopeptides showed significant changes between the two studied groups. The sialylated N-glycopeptide structures LPTQNITFQTESSVAEQEAEFQSPK HexNAc6, Hex3, Neu5Ac2 (derived from the ITIH4 protein) and the structure IVLDPSGSMNIYLVLDGSDSIGASNFTGAK HexNAc5, Hex4, Fuc1 (derived from the CFB protein), with p values of 0.008 and 0.01, respectively, were elevated in NT1 samples compared with controls. In addition, the N-glycopeptide protein sources Ceruloplasmin, Complement factor B, and ITH4 were observed to play an important role in the complement activation and acute-phase response signaling pathways. This may explain the possible association between the biomarkers and pathophysiological effects.

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Immunological and clinicopathological characteristics of C1RL in 2120 glioma patients

Cited by 6 publications

References 37 publications

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

LC-MS/MS-Based Proteomics Approach for the Identification of Candidate Serum Biomarkers in Patients with Narcolepsy Type 1

Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma

LC-MS/MS Quantitation of HILIC-Enriched N-glycopeptides Derived from Low-Abundance Serum Glycoproteins in Patients with Narcolepsy Type 1

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