Expression and prognostic values of ARID family members in breast cancer

Abstract

The ARID family is a superfamily of 15 members containing a domain that interacts with AT-rich DNA elements. However, the expression and prognostic roles of each ARID in breast cancer are still elusive. We used the TCGA and Kaplan-Meier plotter databases to assess the expression and prognostic values of ARID mRNA levels in breast cancer respectively. In the present study, 6 members were significantly lower in tumor tissues than those in the normal tissues, while 6 members were significantly higher. Further assessment of ARID expression in breast cancer with different molecular subtypes, 3 members were significantly higher in no-luminal molecular subtype than those in the luminal molecular subtype, and 6 members were significantly higher. In regard to prognostic values, high expression of ARID1A, ARID2, ARID3B, ARID4A, ARID5A, ARID5B, JARID1A were associated with favorable outcome, while ARID4B and JARID1B were correlated to a worse outcome. We further analyzed the prognostic value of ARID in different intrinsic subtypes and clinicopathological features of breast cancer. We found many meaningful ARID family biomarkers in breast cancer. The relevant results will expound the role of ARID in breast cancer and may further provide new insight to explore the ARID-targeting reagents for treating breast cancer patients.

Keywords: biomarkers; breast neoplasms; prognosis; tumor.

Figure 1

Distinct expression of ARID members in breast cancer patients. (A) The mRNA expression of all the ARID members was assessed in cancer and normal tissues (p values were calculated grouping by Tumor(T)/Normal(N) and using t-test. (B–J) The mRNA expression of ARID1A, ARID1B, ARID2, ARID3A, ARID3C ARID4A, ARID4B, ARID5A, and JARID2 were assessed in different molecular subtypes(p values were calculated grouping by luminal A + luminal B VS. HER2-riched + basal-like and using t-test). (*p < 0.05, **p < 0.01,***p < 0.001).

Figure 2

Prognostic values of ARID members in all breast cancer patients. (A) Prognostic HRs of individual ARID members in all breast cancer. (B–J) Survival curves of ARID1A(Affymetrix IDs: 210649_s_at), ARID2((Affymetrix IDs: 225486_at), ARID3B(Affymetrix IDs: 218964_at), ARID4A(Affymetrix IDs: 230141_at), ARID5A(Affymetrix IDs: 213138_at), ARID5B(Affymetrix IDs: 212614_at), JARID1A(Affymetrix IDs: 215698_at), ARID4B(Affymetrix IDs: 223111_x_at) and JARID1B(Affymetrix IDs: 201548_s_at).

Figure 3

Prognostic values of ARID members in luminal A type breast cancer patients. (A–G) Survival curves of ARID1A(Affymetrix IDs: 210649_s_at), ARID2((Affymetrix IDs:225486_at), ARID4A(Affymetrix IDs: 230141_at), ARID5A(Affymetrix IDs: 213138_at), ARID5B(Affymetrix IDs: 212614_at), JARID1A(Affymetrix IDs: 215698_at) and JARID1B(Affymetrix IDs: 201548_s_at).

Figure 4

Prognostic values of ARID members in luminal B type breast cancer patients. (A–E) Survival curves of ARID2((Affymetrix IDs:225486_at), JARID1B(Affymetrix IDs: 201548_s_at), ARID3B(Affymetrix IDs: 218964_at), ARID5A(Affymetrix IDs: 213138_at) and ARID5B(Affymetrix IDs: 212614_at).

Figure 5

Prognostic values of ARID members in HER2-riched type breast cancer patients. (A–G) Survival curves of ARID1B(Affymetrix IDs: 225181_at), ARID4B(Affymetrix IDs: 223111_x_at), ARID1A(Affymetrix IDs: 210649_s_at), ARID3A(Affymetrix IDs: 205865_at), ARID3B(Affymetrix IDs: 218964_at), ARID5B(Affymetrix IDs: 212614_at) and JARID1A(Affymetrix IDs: 215698_at).

Figure 6

Prognostic values of ARID members in basal-like type breast cancer patients. (A–F) Survival curves of ARID3A(Affymetrix IDs: 205865_at), ARID3B(Affymetrix IDs: 218964_at), ARID4A(Affymetrix IDs: 230141_at), JARID1A(Affymetrix IDs: 215698_at), JARID2(Affymetrix IDs: 203298_s_at), and ARID4B(Affymetrix IDs: 223111_x_at).

Figure 7

ARID1A protein expression is low and related to poor survival in breast cancer patients. (A) Representative IHC staining of ARID1A in (a) normal tissues (n = 32) and (b) tumor tissues (n = 119) (200×). (B) The expression of ARID1A protein in tumor tissues was significantly lower than that in adjacent normal breast tissues (p<0.001). (C) Low ARID1A expression is associated with poor survival in breast cancer patients, based on a Kaplan–Meier analysis of OS (n=119, log-rank test, p=0.035).