Significant prognostic values of aquaporin mRNA expression in breast cancer

Abstract

Introduction: Aquaporins (AQPs), also called water channels, have been shown to have functions in the migration, invasion, and proliferation of human breast tumor cells. Most AQP mRNA expression levels were tested by cell lines, mouse models, and even human breast tissues. However, the mRNA expression of individual AQPs in different clinicopathologic characteristics and prognostic values according to different kinds of classifications of breast cancer patients remains unclear.

Materials and methods: In the current study, we used the Oncomine database, Breast cancer Gene-Expression Miner v4.1, Kaplan-Meier Plotter, and cBioPortal to investigate the expression distribution and prognostic values of AQPs in breast cancer patients.

Results: Our study revealed that the mRNA expression levels of AQP8, AQP9, and AQP10 were upregulated, while those of AQP3, AQP4, AQP5, and AQP7 were downregulated in breast cancer. The clinical database showed that lower mRNA levels of AQP1 were associated with a high Scarff-Bloom-Richardson grade, but AQP9 showed the opposite trend. Further survival analyses indicated that high mRNA expression levels of AQP0, AQP1, AQP2, AQP4, AQP6, AQP8, AQP10, and AQP11 were significantly associated with better relapse-free survival (RFS). Conversely, AQP3 and AQP9 were associated with worse RFS in breast cancer patients, suggesting that these two genes might be potential targets in future chemotherapy.

Discussion: These significant AQP members might be further explored as new biomarkers for breast cancer prognosis, but this needs further study.

Keywords: AQP; biomarker; breast cancer; genetic; prognostic.

Figure 1

The transcription levels of the AQP family in different types of human cancers. Notes: The figure is generated from ONCOMINE with exact thresholds (P-value: 0.01; fold change: 2; gene rank: top 10%). The cell number represents the dataset number that meets all of the thresholds with the color blue for underexpression and color red for overexpression. Cell color is determined by the best gene rank percentile for the analyses within the cell. Abbreviations: AQP, aquaporin; CNS, central nervous system.

Figure 2

The relationship between the AQP family and the SBR and NPI criteria. Notes: (A–F) Box plots of individual AQP member’s expression according to SBR. (G–K) Box plots of individual AQP member’s expression according to NPI. Global significant differences between groups were assessed by Welch’s test, and P<0.05 was considered statistically significant, with Dunnett–Tukey–Kramer’s test computed for each pairwise comparison. Abbreviations: AQP, aquaporin; NPI, Nottingham Prognostic Index; SBR, Scarff–Bloom–Richardson grade.

Figure 3

Survival analyses of the AQP family in breast cancer (RFS in Kaplan–Meier Plotter). Notes: (A) Prognostic HR of individual AQP members in all breast cancers. (B–K) Prognostic significance of individual AQP members in all breast cancers. Abbreviations: AQP, aquaporin; RFS, relapse-free survival.

Figure 4

Survival analyses of the AQP family with different molecular subtypes based on the 2013 St Gallen criteria in breast cancer (RFS in Kaplan–Meier Plotter). Note: (A–P) Prognostic significance of individual AQP members in different molecular subtypes. Abbreviations: AQP, aquaporin; RFS, relapse-free survival.

Figure 5

AQP family gene expression and mutation analysis in invasive breast carcinoma (TCGA Cell 2015 from cBioPortal). Notes: (A) Overall survival Kaplan–Meier estimate in cases with or without AQP alterations. (B) Disease/progression-free survival Kaplan–Meier estimate in cases with or without AQP alterations. (C) Oncoprint represents the distribution and proportion of samples with different types of alterations in the AQP family. The right part of the figure without alterations was not included. Abbreviations: AQP, aquaporin; TCGA, The Cancer Genome Atlas.