GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages

Cao, Wenhui; Fan, Wenjuan; Wang, Fang; Zhang, Yinyin; Wu, Guanghua; Shi, Xiaojing; Shi, Jianzhong; Gao, Fengcai; Yan, Meimei; Guo, Rong; Li, Yingmei; Li, Wei; Du, Chunyan; Jiang, Zhongxing

doi:10.1186/s12967-021-03214-5

Cited by 15 publications

(29 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RNA-seq was analyzed as our previously described [ 22 – 24 ]. Briefly, the Limma package (version 3.40.2) of R software was used to study the differential expression of mRNAs [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Yang

Yan

et al. 2022

J Transl Med

Self Cite

View full text Add to dashboard Cite

Background The phagocytosis checkpoints of CD47/SIRPα, PD1/PDL1, CD24/SIGLEC10, and MHC/LILRB1 have shown inhibited phagocytosis of macrophages in distinct tumors. However, phagocytosis checkpoints and their therapeutic significance remain largely unknown in intrahepatic cholangiocarcinoma (ICC) patients. Methods We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and identified differently expressed genes between tumors and para‐tumors. Then, we investigated the expression of CD68, SIRPα, PD1, and SIGLEC10 by IHC in 81 ICC patients, and the clinical significance of these markers with different risk factors was also measured. Results Tumor infiltration immune cells analysis from the TCGA data revealed that macrophages significantly increased. Further analysis showed that M0 macrophages were significantly higher and M2 macrophages were significantly lower in ICC compared with paracancerous tissues, while there was no significant difference in M1 macrophages. We then examined some of M1 and M2 markers, and we found that M1 markers (iNOS, TNF, IL12A, and B) increased, while M2 markers (ARG1 and CD206) decreased in ICCs compared with paracancerous tissues. Furthermore, the expression of CD68, SIRPα, PD1, and SIGLEC10 increased significantly, but LILRB1 expression did not. We also examined the expression of CD68, SIRPα, PD1, and SIGLEC10 in 81 ICC patients by IHC, which revealed a similar expression pattern to that which emerged from the TCGA data. Upon analyzing the correlation between these markers and the progression of ICC patients, we found that the high expression of CD68, SIRPα, and PD1 are correlated with poor progression among ICC patients, while SIGLEC10 shows no correlation. More SIRPα+ or PD1+ TAMs were observed in the tumor tissues of ICC patients with HBV infections compared to non‐HBV‐infected patients. Multivariate analysis indicated that SIRPα and PD1 expression are independent indicators of ICC patient prognosis. Conclusion Hyperactivated CD47/SIRPα and PD1/PD‐L1 signals in CD68+ TAMs in tumor tissues are negative prognostic markers for ICCs after resection. Furthermore, anti-CD47 in combination with anti-PD1 or CD47/PD1 bispecific antibody (BsAb) may represent promising treatments for ICC. Further studies are also required in the future to confirmed our findings.

show abstract

“…RNA-seq was analyzed as our previously described [ 22 – 24 ]. Briefly, the Limma package (version 3.40.2) of R software was used to study the differential expression of mRNAs [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Yang

Yan

et al. 2022

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cancer and paracancer tissue samples were obtained from the same patient during surgery and immediately embedded into an optimal cutting temperature (OCT) compound. Thereafter, H&E staining was performed, as previously described (Cao et al 2022 ). Briefly, the frozen sections are allowed to warm at room temperature for 5–10 min, and then the rewarmed slices are soaked in water for approximately 30–60 s. The tissues are immersed in distilled water for 1–2 min, while ensuring that the distilled water covers the tissues entirely and that the water is evenly distributed.…”

Section: Methodsmentioning

confidence: 99%

“…All data of normal tissue samples were obtained from 328 pancreases in GTEx V8 release version ( https://gtexportal.org/home/datasets ). The limma package of R software was used to analyze the differentially expressed genes as our previously described (Cao et al 2022 ; Li et al 2019 ; Wang et al 2021 ). Briefly, “Adjusted P < 0.05 and Log2 (FC) > 1 or Log2 (FC) < − 1” were defined as the thresholds for the screening of differentially expressed genes.…”

Section: Methodsmentioning

confidence: 99%

Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients

Sun

et al. 2022

Mol Med

Self Cite

View full text Add to dashboard Cite

Background Pancreatic cancer (PC) is a malignancy with a poor prognosis and high mortality. Surgical resection is the only “curative” treatment. However, only a minority of patients with PC can obtain surgery. Improving the overall survival (OS) rate of patients with PC is still a major challenge. Molecular biomarkers are a significant approach for diagnostic and predictive use in PCs. Several prediction models have been developed for patients newly diagnosed with PC that is operable or patients with advanced and metastatic PC; however, these models require further validation. Therefore, precise biomarkers are urgently required to increase the efficiency of predicting a disease-free survival (DFS), OS, and sensitivity to immunotherapy in PC patients and to improve the prognosis of PC. Methods In the present study, we first evaluated the highly and selectively expressed targets in PC, using the GeoMxTM Digital Spatial Profiler (DSP) and then, we analyzed the roles of these targets in PCs using TCGA database. Results LAMB3, FN1, KRT17, KRT19, and ANXA1 were defined as the top five upregulated targets in PC compared with paracancer. The TCGA database results confirmed the expression pattern of LAMB3, FN1, KRT17, KRT19, and ANXA1 in PCs. Significantly, LAMB3, FN1, KRT19, and ANXA1 but not KRT17 can be considered as biomarkers for survival analysis, univariate and multivariate Cox proportional hazards model, and risk model analysis. Furthermore, in combination, LAMB3, FN1, KRT19, and ANXA1 predict the DFS and, in combination, LAMB3, KRT19, and ANXA1 predict the OS. Immunotherapy is significant for PCs that are inoperable. The immune checkpoint blockade (ICB) analysis indicated that higher expressions of FN1 or ANXA1 are correlated with lower ICB response. In contrast, there are no significant differences in the ICB response between high and low expression of LAMB3 and KRT19. Conclusions In conclusion, LAMB3, FN1, KRT19, and ANXA1 are good predictors of PC prognosis. Furthermore, FN1 and ANXA1 can be predictors of immunotherapy in PCs.

show abstract

“…The RNA-seq transcriptome data of 371 HCC and 50 adjacent tissues were obtained from the TCGA database (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga). The analysis method of RNA-seq is consistent with our previous described [20][21][22]. The Limma package (version: 3.40.2) for R was used to study the differential expression of mRNAs.…”

Section: Gene Expression Data Sets and Functional Enrichmentmentioning

confidence: 99%

Matrix metalloproteinase 1 is a poor prognostic biomarker for patients with hepatocellular carcinoma

Yang

Yan

et al. 2022

Clin Exp Med

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database. The KEGG enrichment pathway using differentially expressed genes included extracellular matrix-receptor interaction, which was correlated with MMPs. We found that among the MMP family, only MMP1, MMP3, MMP8, MMP9, MMP11, MMP12, MMP14, MMP15, MMP20, MMP21, and MMP24 signi cantly increased in HCCs compared with adjacent tissues. Crucially, survival and univariate analyses indicated that only MMPs 1, 9, 12, and 14 predict poor overall survival; however, multivariate Cox analysis and a nomogram demonstrated that only MMP1 is a poor prognostic biomarker for HCCs. In addition, we observed a signi cant enrichment of uncharacterized cells but decreased macrophages in HCC tissues. Consistent with decreased macrophages in HCCs, MMP1 was negatively associated with macrophages but positively correlated with uncharacterized cells, indicating that the main producer of MMP1 is uncharacterized cells. Furthermore, MMP1 expression was negatively correlated with immune responses of HCCs. Taken together, our ndings indicated that MMP1 is a poor and predominant prognostic biomarker for patients with HCC, and that anti-MMP1 may be a novel therapy that is worth studying in depth.MMPs can promote cancer progression by increasing cancer cell growth, migration, invasion, metastasis, and angiogenesis.[6] MMPs exert these effects by cleaving a diverse group of substrates, which include not only structural components of the extracellular matrix (ECM), but also growth-factor-binding proteins, growth-factor precursors, receptor tyrosine kinases, cell-adhesion molecules, and other proteinases. [6] Direct evidence for a role of MMPs in tumor progression has been provided by xenograft experiments that have used cancer cells with decreased and increased expression levels of MMPs or tissue inhibitors of metalloproteinases (TIMPs), and also by carcinogenesis experiments with mice that either lacked a speci c MMP or TIMP-1 or had organ-speci c MMP or TIMP-1 overexpression.[7-13] MMPs are upregulated in almost every type of human cancer, including HCCs, and their expression is often associated with poor survival.[6, 14-19] However, there is no consensus on which MMP plays the predominant role in HCCs, which limits their clinical predictive value for the prognosis of patients with HCC. Therefore, the prognostic role of MMP members in HCCs still needs to be fully uncovered.In the present study, we characterized the gene expression pro les from the Cancer Genome Atlas (TCGA) database (https://portal.gdc.com). We analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the TCGA database. Am...

show abstract

GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages

Cited by 15 publications

References 94 publications

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Identification and prognostic analysis of biomarkers to predict the progression of pancreatic cancer patients

Matrix metalloproteinase 1 is a poor prognostic biomarker for patients with hepatocellular carcinoma

Contact Info

Product

Resources

About