Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis

Ren, Liwen; Yi, Jie; Yang, Yihui; Li, Wan; Zheng, Xiangjin; Liu, Jinyi; Li, Sha; Yang, Hong; Zhang, Yizhi; Ge, Binbin; Zhang, Sen; Fu, Weiqi; Dong, Dexin; Du, Guanhua; Wang, Xifu; Wang, Jinhua

doi:10.1016/j.phrs.2022.106376

Cited by 35 publications

(29 citation statements)

References 52 publications

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“…Notably, our findings showed a decreased proportion of M1 cells and an increased proportion of M2 cells under high stress, which was consistent with other evidence of anti-inflammatory effects that decreased the expression of chemokine genes in six subsets of T cells. We also found SPP1 + Mac0 with high expression of APOC1 which promoted M2 polarization of macrophages ( 79 ), indicating that SPP1 + Mac0 was involved in the polarization of macrophages. We infer that the balance of M1 and M2 macrophages may play a crucial role in the development of ACS and even maybe a therapeutic target for ACS.…”

Section: Discussionmentioning

confidence: 74%

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Wang

Long

et al. 2023

Front. Immunol.

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IntroductionHigh stress in the compartment surrounded by the deep fascia can cause acute compartment syndrome (ACS) that may result in necrosis of the limbs. The study aims to investigate the cellular heterogeneity of the deep fascia in ACS patients by single-cell RNA sequencing (scRNA-seq).MethodsWe collected deep fascia samples from patients with ACS (high-stress group, HG, n=3) and patients receiving thigh amputation due to osteosarcoma (normal-stress group, NG, n=3). We utilized ultrasound and scanning electron microscopy to observe the morphologic change of the deep fascia, used multiplex staining and multispectral imaging to explore immune cell infiltration, and applied scRNA-seq to investigate the cellular heterogeneity of the deep fascia and to identify differentially expressed genes.ResultsNotably, we identified GZMK+interferon-act CD4 central memory T cells as a specific high-stress compartment subcluster expressing interferon-related genes. Additionally, the changes in the proportions of inflammation-related subclusters, such as the increased proportion of M2 macrophages and decreased proportion of M1 macrophages, may play crucial roles in the balance of pro-inflammatory and anti-inflammatory in the development of ACS. Furthermore, we found that heat shock protein genes were highly expressed but metal ion-related genes (S100 family and metallothionein family) were down-regulated in various subpopulations under high stress.ConclusionsWe identified a high stress-specific subcluster and variations in immune cells and fibroblast subclusters, as well as their differentially expressed genes, in ACS patients. Our findings reveal the functions of the deep fascia in the pathophysiology of ACS, providing new approaches for its treatment and prevention.

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Section: Discussionmentioning

confidence: 74%

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Wang

Long

et al. 2023

Front. Immunol.

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“…Recent researches have shown that immune infiltration is associated with the initiation, progression, and metastasis in human cancers ( Stenstrom et al, 2021 ; Ren et al, 2022 ; Shan et al, 2022 ). Several algorithms, such as TIMER, EPIC, QUANTISEQ, XCELL, MCPCOUNTER, CIBERSORT, CIBERSORT-ABS, and TIDE, were applied to explore the correlation between LIPT1 expression and the infiltration of different immune cells in pan-cancer.…”

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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“…By interacting with CD163 and CD206, APOC1 boosted macrophage polarization toward M2 by increasing its expression in M2 or TAM. Additionally, through secreting CCL5, macrophages overexpressing APOC1 aided in the spread of renal cell cancer cells [13]. According to Chan et al's research, TAMs have high levels of APOE, APOC1, and SPP1 expression, which results in an anti-infammatory macrophage phenotype [27].…”

Section: Discussionmentioning

confidence: 99%

“…Although APOC1 has been observed to be crucial for the growth and metastasis of a number of malignancies [11], the underlying mechanisms have not been fully understood, particularly with regard to its function and part in tumor immunity [12]. Liwen Ren et al established that APOC1 is an immunological biomarker that controls macrophage polarization and encourages tumor dissemination through extensive pan-cancer studies, which revealed that APOC1 is intimately connected to the infltration of diferent immune cells in a range of malignancies [13]. We conducted single-cell RNA sequencing (scRNA-seq) in one patient with CRC liver metastasis to further examine why APOC1 is highly expressed in CRC tissues.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis

Tang

Liu

et al. 2023

Journal of Oncology

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Background. Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene’s expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC. Methods. The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1’s cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan–Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration. Results. When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs. Conclusion. Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.

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Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis

Cited by 35 publications

References 52 publications

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

Single-cell RNA-seq reveals cellular heterogeneity from deep fascia in patients with acute compartment syndrome

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

Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis

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