Pan-Cancer Analysis of Prognostic and Immune Infiltrates for CXCs

Long, Li; Yao, Wenchao; Yan, Sen; Dong, Xiaowei; Lv, Zhenyi; Jing, Qingxu; Wang, Qiang; Ma, Biao; Hao, Chenjun; Xue, Dongbo; Wang, Dawei

doi:10.3390/cancers13164153

Cited by 14 publications

(27 citation statements)

References 38 publications

(43 reference statements)

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“…For instance, CD93 was recently found to improve tumor vascular functions to promote T-cell infiltration and antitumor immunity after blockade of its pathway ( Sun et al, 2021 ). In addition, we also found that CD93 expression was positively related to almost all immune-related genes, which are known to promote the growth of tumor cells and tumor angiogenesis as well as contribute to tumor metastasis ( Li et al, 2021 ; Schaafsma et al, 2021 ) in nearly all cancers, which further demonstrated the importance of CD93 in the process of immune regulation.…”

Section: Discussionsupporting

confidence: 53%

CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

Zhang

Zheng

Ding

et al. 2022

Front. Cell Dev. Biol.

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Background: The clinical implementation of immune-checkpoint inhibitors (ICIs) targeting CTLA4, PD-1, and PD-L1 has revolutionized the treatment of cancer. However, the majority of patients do not derive clinical benefit. Further development is needed to optimize the approach of ICI therapy. Immunotherapy combined with other forms of treatment is a rising strategy for boosting antitumor responses. CD93 was found to sensitize tumors to immune-checkpoint blocker therapy after the blockade of its pathway. However, its role in immune and ICB therapy across pan-cancer has remained unexplored.Methods: In this study, we provide a comprehensive investigation of CD93 expression in a pan-cancer manner involving 33 cancer types. We evaluated the association of CD93 expression with prognosis, mismatch repair, tumor mutation burden, and microsatellite instability, immune checkpoints, tumor microenvironment, and immune using multiple online datasets, including The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Tumor Immune Estimation Resource database, and Tumor Immune Single-cell Hub.Results: CD93 expression varied strongly among cancer types, and increased CD93 gene expression was associated with poor prognosis as well as higher immune factors in most cancer types. Additionally, the level of CD93 was significantly correlated with MMR, TMB, MSI, immune checkpoints, TME, and immune cell infiltration. Noticeably, our results mediated a strong positive contact between CD93 and CAFs, endothelial cells, myeloid dendritic cells, hematopoietic stem cells, mononuclear/macrophage subsets, and neutrophils while a negative correlation with Th1, MDSC, NK, and T-cell follicular helper in almost all cancers. Function analysis on CD93 revealed a link between itself and promoting cancers, inflammation, and angiogenesis.Conclusion: CD93 can function as a prognostic marker in various malignant tumors and is integral in TME and immune infiltration. Inhibition of the CD93 pathway may be a novel and promising strategy for immunotherapy in human cancer. Further explorations of the mechanisms of CD93 in the immune system may help improve cancer therapy methods.

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Section: Discussionsupporting

confidence: 53%

CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

Zhang

Zheng

Ding

et al. 2022

Front. Cell Dev. Biol.

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“…Single-cell transcriptome sequencing is a key technique for analyzing the underlying functions of candidate molecules at single-cell levels ( He et al, 2021 ; Li et al, 2021 ). In retinoblastoma (RB), the expression of LIPT1 was negatively associated with cell cycle, DNA repair response, EMT and invasion.…”

Section: Resultsmentioning

confidence: 99%

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Liu

Luo²,

Yan³

et al. 2022

Front. Genet.

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As a key copper homeostasis-related molecule, lipoyltransferase 1 (LIPT1) is an essential enzyme for the activation of mitochondrial 2-ketoacid dehydrogenase, participating in fatty acylation. However, the biological significances of LIPT1 in the pan-cancer are unclear. Here, we comprehensively analyzed the functional characteristics of LIPT1 in human cancers and its roles in immune response. We found that LIPT1 was down-regulated in some cancers. And LIPT1 overexpression is associated with favorable prognosis in these patients, such as breast cancer, clear cell renal cell carcinoma, ovarian cancer and gastric cancer. We also explored the mutational status and methylation levels of LIPT1 in human cancers. Gene enrichment analysis indicated that abnormally expressed LIPT1 was significantly associated with immune cells infiltration, such as B cells, CD8+ T cells and cancer-associated fibroblast cells. The result from single cell sequencing reflected the important roles of LIPT1 in the regulation of several biological behaviors of cancer cells, such as DNA damage response and cell apoptosis. Taken together, our research could provide a comprehensive overview about the significances of LIPT1 in human pan-cancer progression, prognosis and immune.

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“…Furthermore, our study also revealed the co-expression of FDX1 with immune-related genes, including chemokine, chemokine receptor, MHC, immunostimulatory, immunosuppressive, and immune checkpoint-related genes. FDX1 expression is closely correlated with almost all immune-related genes and contributes to tumor development ( Li et al, 2021 ; Schaafsma et al, 2021 ). Overall, these results indicate that the regulation of FDX1 expression may be a promising strategy to increase the efficacy of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis

et al. 2022

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Ferredoxin 1 (FDX1) functions by transferring electrons from NADPH to mitochondrial cytochrome P450 via the ferredoxin reductase and is the key regulator in copper-dependent cell death. Although mounting evidence supports a vital role for FDX1 in tumorigenesis of some cancers, no pan-cancer analysis of FDX1 has been reported. Therefore, we aimed to explore the prognostic value of FDX1 in pan-cancer and investigate its potential immune function. Based on data from The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, Human Protein Atlas, and Gene Set Cancer Analysis, we used a range of bioinformatics approaches to explore the potential carcinogenic role of FDX1, including analyzing the relationship between FDX1 expression and prognosis, DNA methylation, RNA methylation-related genes, mismatch repair (MMR) gene, microsatellite instability (MSI), tumor mutation burden (TMB), tumor microenvironment (TME), immune-related genes, and drug sensitivity in different tumors. The results show that FDX1 was lowly expressed in most cancers but higher in glioblastoma multiforme, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Moreover, FDX1 expression was positively or negatively associated with prognosis in different cancers. FDX1 expression was significantly associated with DNA methylation in 6 cancers, while there was a correlation between FDX1 expression and RNA methylation-related genes and MMR gene in most cancers. Furthermore, FDX1 expression was significantly associated with MSI in 8 cancers and TMB in 10 cancers. In addition, FDX1 expression was also significantly correlated with immune cell infiltration, immune-related genes, TME, and drug resistance in various cancers. An experiment in vitro showed FDX1 is downregulated by elesclomol, resulting in inhibiting cell viability of bladder cancer, clear cell renal cell carcinoma, and prostate cancer cells. Our study reveals that FDX1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity.

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Pan-Cancer Analysis of Prognostic and Immune Infiltrates for CXCs

Cited by 14 publications

References 38 publications

CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

CD93 Correlates With Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Ferredoxin 1 is a cuproptosis-key gene responsible for tumor immunity and drug sensitivity: A pan-cancer analysis

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