Bioinformatics Analysis of the Prognostic Significance of CAND1 in ERα-Positive Breast Cancer

Abstract

The identification of novel prognostic biomarkers for breast cancer is an unmet clinical need. Cullin-associated and neddylation-dissociated 1 (CAND1) has been implicated in mediating carcinogenesis in prostate and lung cancers. In addition, CAND1 is an established prognostic biomarker for worse prognosis in liver cancer. However, the prognostic significance of CAND1 in breast cancer has not yet been explored. In this study, Breast Cancer Gene-Expression Miner (Bc-GenExMiner) and TIMER2.0 were utilized to explore the mRNA expression of CAND1 in ERα-positive breast cancer patients. The Kaplan-Meier plotter was used to explore the relationship between CAND1 expression and several prognostic indicators. The Gene Set Cancer Analysis (GSCA) web server was then used to explore the pathways of the genes that correlate with CAND1 in ERα-positive breast cancer. Immune infiltration was investigated using Bc-GenExMiner. Our bioinformatics analysis illustrates that breast cancer patients have higher CAND1 compared to normal breast tissue and that ERα-positive breast cancer patients with a high expression of CAND1 have poor overall survival (OS), distant metastasis-free survival (DMFS), and relapse-free survival (RFS) outcomes. Higher CAND1 expression was observed in histologic grade 3 compared to grades 2 and 1. Our results revealed that CAND1 positively correlates with lymph nodes and negatively correlates with the infiltration of immune cells, which is in agreement with published reports. Our findings suggest that CAND1 might mediate invasion and metastasis in ERα-positive breast cancer, possibly through the activation of estrogen and androgen signaling pathways; however, experiments should be carried out to further explore the role of CAND1 in activating the androgen and estrogen signaling pathways. In conclusion, the results suggest that CAND1 could be used as a potential novel biomarker for worse prognosis in ERα-positive breast cancer.

Keywords: CAND1; Erα; bioinformatics; breast cancer; metastasis; prognosis; survival.

Figure 1

(a) CAND1 mRNA expression in normal, tumor-adjacent, ERα-positive and -negative breast cancer tissues using bc-GenExMiner; (b) CAND1 mRNA expression in normal and breast cancer tissue using TIMER2.0. ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 2

Survival curves evaluating the prognostic value of CAND1 in ERα-positive breast cancer patients: (a) Analysis for OS; (b) analysis for DMFS; (c) analysis for RFS.

Figure 3

Pearson’s correlation coefficient between CAND1 mRNA and several gene markers of immune cells in ERα-positive breast cancer patients, including T cells, B cells, monocytes, macrophages M1 and M2, and neutrophils. **** p < 0.0001.

Figure 4

Plots evaluating CAND1 expression in ERα-positive breast cancer patients according to different clinical parameters: (a) Analysis for lymph nodes examined positive; (b) analysis for neoplasm histologic grades; (c) analysis for ERα-positive breast cancer patients who received hormone therapy and patients who did not receive hormone therapy. * p < 0.05 and ** p < 0.01.

Figure 5

Schematic presentation of the experimental design followed in this study.

Figure 6

Heat map showing the activated and inhibited pathways based on genes that significantly correlate with CAND1 in ERα-positive breast cancer patients.