High NCALD expression predicts poor prognosis of cytogenetic normal acute myeloid leukemia

Song, Yemei; Zhang, Weilong; He, Xue; Liu, Xiaoni; Yang, Ping; Wang, Jing; Hu, Kai; Liu, Weiyou; Zhang, Xiuru; Jing, Hongmei; Yuan, Xiaoliang

doi:10.1186/s12967-019-1904-5

Cited by 11 publications

(12 citation statements)

References 44 publications

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“…NCALD was related to prognosis in cancers. For instance, high expression of NCALD predicts worse survival of acute myeloid leukemia 44 . However, more studies support the opposite observation that NCALD low expression implies poor prognosis in cancer.…”

Section: Discussionmentioning

confidence: 96%

“…NCALD encodes a cognate of bovine neurocalcin delta, 41 and expressed in many tissues, comprising normal brain, lymphoblasts, and ovarian tissue 42 . The association of NCALD with cancer was unclear until recent years when a few studies indicated its dysregulated function in prostate cancer, 43 lung cancer, 13 and normal acute myeloid leukemia 44 . We determined that NCALD expression was downregulated at the transcript and protein levels in OC specimens and drug‐resistant OC cells and specimens in contrast to controls (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

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NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Dong

Yin

Zhu

et al. 2020

J of Cellular Biochemistry

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Drug resistance, an impenetrable barrier in the treatment of ovarian cancer (OC), is often associated with poor outcomes. Hence, it is urgent to discover new factors controlling drug resistance and survival. The association between neurocalcin delta (NCALD) and cancer drug resistance is poorly understood. Here, we reveal that NCALD messenger RNA expression, probably regulated by DNA methylation and microRNAs, was significantly downregulated in at least three independent microarrays covering 633 ovarian carcinomas and 16 normal controls, which includes the Cancer Genome Atlas (TCGA) ovarian cohort. In the sub‐groups of the TCGA cohort, NCALD was suppressed in 90 platinum‐resistant tissues vs in 197 sensitive tissues. It is consistent with the quantitative reverse transcription polymerase chain reaction results revealing gene downregulation in carboplatin‐resistant SKOV3 and HeyA8 OC cells as compared with that in controls. Low expression of NCALD predicted poor overall survival (OS) in sub‐groups of 1656 patients, progression‐free survival (PFS) in 1435 patients, and post‐progression survival (PPS) in 782 patients according to Kaplan‐Meier plotter covering 1815 OC patients. Comprehensive bioinformatic analyses strongly implicated NCALD in the regulation of drug resistance, probably via competing for endogenous RNA (ceRNA) interactions with CX3CL1 and tumor immune‐microenvironment. NCALD acted as a ceRNA for CX3CL1 in 21 different cancers includes OC according to Starbase. These two genes negatively correlated with tumor purity and positively correlated with infiltration levels of neutrophils and dendritic cells in OC. The combined low expression of NCALD and CX3CL1 showed better prognosis potential for OS, PFS, and PPS in the 1815 OC patients than any of the individually tested genes. In summary, NCALD acts as a ceRNA for CX3CL1, and its downregulation may affect drug resistance and prognosis in OC. Thus, NCALD could be a new therapeutic target for anticancer therapy and a new biomarker for survival prediction in OC.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Dong

Yin

Zhu

et al. 2020

J of Cellular Biochemistry

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“…NCALD consists of four EF hand motifs, but only three can bind to calcium, which alters the conformation of the NCALD protein [10]. Studies have found that NCALD expression is associated with the prognosis of acute myeloid leukemia and non-small cell lung cancer, indicating its clinical potential as a prognosis biomarker [11,12]. In ovarian cancer, Isaksson's study showed that low expression of NCALD predicts poor prognosis [13].…”

Section: Introductionmentioning

confidence: 99%

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer

Feng

2020

J Ovarian Res

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Background: Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis. Methods: High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter. Results: In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-β signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS. Conclusions: NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.

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“…Ahn et al (7) reported that in patients with NK-AML, the presence of mutated chromatin, RNA-splicing genes or both was associated with poor survival. In general, these studies (3)(4)(5)(6)(7) have indicated high genetic heterogeneity in NK-AML. Patients with NK-AML exhibit marked differences in terms of prognosis (8).…”

Section: Introductionmentioning

confidence: 99%

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype

Dong

Zhang

et al. 2020

Oncol Lett

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Acute myeloid leukemia with normal karyotype (NK-AML) is a group of diseases with high heterogeneity and immunological processes are significantly associated with its initiation and development. The implication of the immunogenomic landscape in the prognosis of patients with NK-AML has remained largely elusive. In the present study, the expression profiles of immune-related genes (IRGs) were examined and their association with overall survival (OS) was determined in 60 patients with NK-AML from The Cancer Genome Atlas dataset and 104 patients from the Gene Expression Omnibus (GEO) dataset no. GSE71014. Univariate Cox regression analysis was used to identify 42 and 203 IRGs in the two respective cohorts, which were significantly associated with OS in NK-AML. A risk model was constructed based on the regression coefficient and expression values of nine survival-associated IRGs shared between the two datasets [zinc finger CCCH-type containing, antiviral 1 like; transferrin receptor; suppressor of cytokine signaling 1; ELAV like RNA binding protein 1; roundabout guidance receptor 3; unc-93 homolog B1, Toll-like receptor signaling regulator; protein tyrosine phosphatase non-receptor type 6; interleukin 2 receptor subunit alpha (IL2RA) and IL3RA]. Using this risk model, patients with NK-AML may be divided into high-and low-risk groups in prognostic predictions. The area under the receiver operating characteristic curve for predicting OS was 0.793. The prognostic role of this risk model was successfully verified in another independent cohort (GEO dataset no. GSE71014). The prognostic risk score was positively associated with age and fms related receptor tyrosine kinase 3 mutation and correlated with infiltration by T regulatory cells. In conclusion, the results of the present study provided an IRG score model for prognostic stratification of adult patients with NK-AML, as well as further insight into the implication of IRGs in NK-AML that may lead to the development of novel immunotherapy approaches for this disease.

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High NCALD expression predicts poor prognosis of cytogenetic normal acute myeloid leukemia

Cited by 11 publications

References 44 publications

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype

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