Abstract

BackgroundLow 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.MethodsHigh-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.ResultsIn 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.ConclusionsNCALD 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.

Highlights

  • Low expression of Neurocalcin delta (NCALD)(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis

  • Characteristics of patients Data from 491 ovarian cancer patients were downloaded from the The Cancer Genome Atlas (TCGA), and 204 patients without chemotherapy outcomes were excluded. 287 ovarian cancer patients with gender, age, grade, The international federation of gynecology and obstetrics (FIGO) stage, survival outcome, chemotherapy outcome, and NCALD mRNA expression were obtained

  • In summary, our study demonstrates that NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer

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Summary

Introduction

Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. The molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. More than 75% of ovarian cancer patients are stage III or IV at the time of initial diagnosis, with a 5-year survival rate was less than 30% [1, 2]. The standard treatment plan for the initial diagnosis of ovarian cancer is optimal debulking combined with platinum-based chemotherapy [3]. Recent advances in radical surgery and chemotherapy have improved the treatment outcomes for ovarian cancer. In order to improve the prognosis of ovarian cancer patients, new biomarkers which predict chemotherapy resistance and treatment strategies to overcome resistance are needed

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