Identification of the Integrated Prognostic Signature Associated with Immuno-relevant Genes and Long Non-coding RNAs in Acute Myeloid Leukemia

Zhao, Chunxia; Wang, Yulu; Sharma, Amit; Wang, Zifeng; Zheng, Chafeng; Wang, Ying; Wang, Yun; Li, Pingping; Liu, Jiachen; Zhan, Xulong; Schmidt‐Wolf, Ingo G.H.; Tu, Famei

doi:10.1080/07357907.2022.2096230

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…The prognostic relationships of CSRP1 have been studied in several different cancer types. CSRP1 was included in a gene signature that identified a high-risk subgroup of acute myeloid leukemia with worse prognosis [ 30 ]. In contrast, in prostate cancer, it was reported that a high expression of CSRP1 was associated with longer DFS [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CANLI

2023

Turkish Journal of Medical Sciences

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Background/aim Cysteine and glycine-rich protein 1 (CSRP1) is involved in the cysteine-rich protein family and is a marker of smooth muscle lineages. In colon cancer, the expression of this gene is associated with poor prognosis. In this study, the aim was to reevaluate its prognostic relationship in independent cohorts and explore potential underlying biological processes that are linked to aggressive behavior in tumors with high CSRP1 expression, such as epithelial-to-mesenchymal transition (EMT), stromal fractions in the tumor microenvironment, and consensus molecular subtypes (CMSs). Materials and methods RNA sequencing (RNAseq)-, microarray-, and single-cell RNAseq (scRNAseq)-based transcriptomic data were obtained from public databases. The EMT score was calculated based on the expression of E-cadherin and vimentin genes using a previously published method. The stromal score generated by the ESTIMATE method was utilized for the analysis of correlation with the CSRP1 expression. The scRNAseq data were analyzed via the Seurat R package. The immunohistochemistry-based protein level expression of CSRP1 was evaluated using the Human Protein Atlas database. Results Lower CSRP1 expression was noted in colon tumors compared to normal colon tissue. Patients with a high CSRP1 expression had shorter recurrence-free, overall, and disease-specific survivals in the GSE39582 and GSE17536 datasets (p < 0.05). The methylation level of the CSRP1 gene was negatively correlated (r = −0.57, p < 0.0001) with CSRP1 expression in The Cancer Genome Atlas colon adenocarcinoma dataset. CSRP1 expression was positively correlated with the expression of mesenchymal markers, EMT score, and stromal score obtained via the ESTIMATE method. CMS4 colon tumors had a significantly higher CSRP1 expression compared to other CMSs. Analysis of the scRNAseq data revealed that CSRP1 was expressed by epithelial cells and cancer-associated fibroblasts in the colorectal tumor microenvironment, which was also confirmed by the protein expression data from the Human Protein Atlas database. Conclusion CSRP1 expression is associated with CMS4, a more mesenchymal stroma-rich molecular profile, and poor prognosis in colon cancer.

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Section: Discussionmentioning

confidence: 99%

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CANLI

2023

Turkish Journal of Medical Sciences

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“…Given the potential role of CSRP1 in various cancer types and our previous work [ 23 ], which identified a prognostic model containing DAXX, PSMB8, CSRP1, RAC2, and PTPN6, this current study is dedicated to investigating the role of the CSRP1 gene in acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 99%

CSRP1 gene: a potential novel prognostic marker in acute myeloid leukemia with implications for immune response

Zhao,

Wang,

Wang

et al. 2024

Discov Onc

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Background Acute myeloid leukemia, constituting a majority of leukemias, grapples with a 24% 5-year survival rate. Recent strides in research have unveiled fresh targets for drug therapies. LIM-only, a pivotal transcription factor within LIM proteins, oversees cell development and is implicated in tumor formation. Among these critical LIM proteins, CSRP1, a Cysteine-rich protein, emerges as a significant player in various diseases. Despite its recognition as a potential prognostic factor and therapeutic target in various cancers, the specific link between CSRP1 and acute myeloid leukemia remains unexplored. Our previous work, identifying CSRP1 in a prognostic model for AML patients, instigates a dedicated exploration into the nuanced role of CSRP1 in acute myeloid leukemia. Methods R tool was conducted to analyze the public data. qPCR was applied to evaluate the expression of CSRP1 mRNA for clinical samples and cell line. Unpaired t test, Wilcoxon Rank Sum test, KM curves, spearman correlation test and Pearson correlation test were included in this study. Results CSRP1 displays notable expression variations between normal and tumor samples in acute myeloid leukemia (AML). It stands out as an independent prognostic factor for AML patients, showing correlations with clinical factors like age and cytogenetics risk. Additionally, CSRP1 correlates with immune-related pathways, immune cells, and immune checkpoints in AML. Furthermore, the alteration of CSRP1 mRNA levels is observed upon treatment with a DNMT1 inhibitor for THP1 cells. Conclusion The CSRP1 has potential as a novel prognostic factor and appears to influence the immune response in acute myeloid leukemia. Additionally, there is an observed association between CSRP1 and DNA methylation in acute myeloid leukemia.

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“…In contrast, higher CSRP1 expression was reported in breast cancers, which is related to RNA-binding functions [ 10 ], suggesting its oncogenic potentials. Consistently, higher expression of CSRP1 helps identify a high-risk subgroup of acute myeloid leukemia (AML) with worse prognosis [ 11 ]. Therefore, CSRP1 seems to display completely different roles in different tumor types.…”

Section: Introductionmentioning

confidence: 99%

CSRP1 Promotes Colon Adenocarcinoma Growth and Serves as an Independent Risk Biomarker for Worse Prognosis

Zhao²,

Meng

et al. 2023

Genetics Research

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Background. Cysteine and Glycine Rich Protein 1 (CSRP1) belongs to the cysteine-rich protein family, which contains a unique double-zinc finger motif and is important for development and cellular differentiation. Abnormal expression of CSRP1 was reported within several malignancies such as prostate cancer and acute myeloid leukemia. Here, we explored function of CSRP1 within colon adenocarcinoma (COAD) for the first time. Methods. The mRNA levels of CSRP1 in COADs were obtained from TCGA datasets. CSRP1 protein expressions in COADs were tested via immunohistochemistry staining. Patients’ prognosis was evaluated using both univariate analysis and multivariate analysis. Two human COAD originated cancer cell lines, Caco-2, and HT-29, were used for cellular experiments including shRNA knockdown, proliferation assay, and migration assay. In vivo model was established using nude mice xenografts to further validate the role of CSRP1 in COAD progression. Results. The mRNA levels of CSRP1 are elevated in COAD specimens from patients with more advanced tumor stages and higher Carcinoembryonic Antigen (CEA) levels. In addition, higher CSRP1 mRNA level indicates worse COAD prognosis. Consistently, higher CSRP1 protein expression is correlated with worse overall survival according to both univariate and multivariate analysis, indicating that CSRP1 is a new COAD prognostic factor. Furthermore, COAD cells transfected with CSRP1-shRNAs exhibit attenuated proliferation and migration capacities. Finally, growth of xenografts originated from CSRP1-knockdown cells is inhibited comparing to the control ones. Conclusions. Expression of CSRP1 is positively correlated with COAD progression, which can promote tumor growth and migration. Higher CSRP1 can is a novel independent prognostic factor of COAD.

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Identification of the Integrated Prognostic Signature Associated with Immuno-relevant Genes and Long Non-coding RNAs in Acute Myeloid Leukemia

Cited by 6 publications

References 27 publications

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CSRP1 expression is associated with a mesenchymal, stroma-rich tumor profile and poor prognosis in colon cancer

CSRP1 gene: a potential novel prognostic marker in acute myeloid leukemia with implications for immune response

CSRP1 Promotes Colon Adenocarcinoma Growth and Serves as an Independent Risk Biomarker for Worse Prognosis

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