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

Abstract

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.

Long non-coding RNA MIDEAS-AS1 inhibits growth and metastasis of triple-negative breast cancer via transcriptionally activating NCALD

“…AF131215.5 was a lncRNA whose function remained unclear in cancer [ 31 , 32 ]. Interestingly, NCALD (neurocalcin delta) expression was lower in lung adenocarcinoma tissues [ 33 ], and patients with higher NCALD levels exhibited a higher survival rate [ 34 , 35 ]. Among these genes, we hypothesized that NCALD, the tumor suppressor gene, might be a potential target of MIDEAS-AS1 in breast cancer.…”

“…Previous studies had found that NCALD was not only involved in cell apoptosis, cell cycle progression and other biological processes in several cancers [ 36 ], but also associated with the prognosis of cancers [ 34 , 35 ]. However, there is no report about the function of NCALD in breast cancer.…”

SENP3 promotes tumor progression and is a novel prognostic biomarker in triple-negative breast cancer

“…KIF1C is a kinesin-like motor protein that mediates the resistance of mouse macrophages to anthrax lethal factor and is currently less studied in tumors ( 34 ). Involved in calcium signaling as well as G protein-coupled receptor signaling, NCALD is part of the neuronal calcium sensor family ( 35 ), and lower expression of NCALD in tumors is also considered to be associated with poor prognosis ( 36 ). GTF3A is considered to be associated with the migration of different types of cancer, and in colorectal cancer, high GTF3A and GTF3B expression seems to be associated with poor prognosis ( 37 ).…”

The role of DNA methylation in ovarian cancer chemoresistance: A narrative review

“…Moreover, reduced NCALD expression was more prevalent in poorly differentiated tumors 94 . Feng et al validated these findings and also outlined that NCALD expression was significantly lower in the tumor tissue from chemoresistant OC patients 95 . Although these studies provided transcriptomic data, neither assessed the relationship between NCALD methylation and gene expression.…”

“…validated these findings and also outlined that NCALD expression was significantly lower in the tumor tissue from chemoresistant OC patients. 95 Although these studies provided transcriptomic data, neither assessed the relationship between NCALD methylation and gene expression. To that end, in a more recent study, 450 K Infinium Methylation BeadChip analysis showed that there was greater methylation at three specific CpG sites within the NCALD gene in chemoresistant compared to chemosensitive HGSOC.…”