The loss of nuclear expression of single-stranded DNA binding protein 2 of gastric adenocarcinoma and its prognostic role: Analysis of molecular subtype

Abstract

Single-stranded DNA binding protein 2 (SSBP2) is ubiquitously expressed, with several studies reporting it to be a tumor suppressor. We investigated SSBP2 expression and its clinicopathological significance in gastric cancer. SSBP2 expression was examined by immunohistochemistry in 539 gastric cancer sections. The cases were divided into three subtypes, namely, Epstein–Barr virus-associated (EBV), microsatellite unstable, and others (microsatellite stable and EBV negative), based on the molecular classification of The Cancer Genome Atlas (TCGA). Cases were also divided into two subgroups according to the amplification status of human epidermal growth factor receptor 2 (HER2). Most cases showed SSBP2 positivity, and only 24 (4.5%) cases displayed negative nuclear expression. Loss of nuclear expression correlated significantly with high pT category ( P = 0.001), nodal metastasis ( P = 0.002), and stage of progression ( P = 0.005), with no correlation between molecular characteristics and SSBP2 expression. All HER2 amplification cases displayed positive SSBP2 expression. Negative SSBP2 cases showed significantly shorter recurrence-free survival (RFS) compared to positive SSBP2 cases ( P = 0.008). Loss of nuclear expression of SSBP2 was significantly associated with shorter RFS in the microsatellite stable and EBV negative groups ( P = 0.002), as well as the HER2 negative group ( P = 0.007). However, there were no statistically significant differences in multivariate analyses. Loss of nuclear expression of SSBP2 was a poor prognostic factor, associated with stage of progression and recurrence, and showed no significant difference in molecular characteristics, including TCGA subtype and HER2 status.

Loss of Single-Stranded DNA Binding Protein 2 Expression Is Associated with Aggressiveness and Poor Overall Survival in Patients with Invasive Breast Carcinoma

“…Bang et al reported that loss of nuclear SSBP2 expression was correlated with higher pT stage, nodal metastasis, and higher AJCC stage in gastric adenocarcinoma. They also found that loss of nuclear SSBP2 expression was associated with poorer RFS in a microsatellite stable and Epstein–Barr virus (EBV)-negative group and HER2-negative group [ 14 ]. Chung et al reported that loss of nuclear SSBP2 expression was observed in 34.3% of colorectal adenocarcinoma (CRA) and 76.3% of metastatic CRA cases, and they noted that loss of nuclear SSBP2 expression was associated with higher pT stage, vascular invasion, and poorer OS in CRA [ 15 ].…”

“…who were blinded to the clinicopathological parameters and the patient clinical outcomes. According to previous reports [ 14 , 16 ], we subdivided the patients into a positive subgroup (proportion of positive tumor cells >10% of the total tumor cells) and a negative subgroup (proportion of positive tumor cells <10% of the total tumor cells).…”

“…LDB1 is a protein that is reported to be involved in tumorigenesis in leukemia, head and neck cancer, and colon cancer [ 9 ]. The role of SSBP2 in human malignancies has been studied in several solid tumors and myeloid leukemia [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Regarding whether SSBP2 function is a tumor suppressor or tumor promoter, its exact role remains unclear.…”

“…Regarding whether SSBP2 function is a tumor suppressor or tumor promoter, its exact role remains unclear. Several studies have demonstrated that SSBP2 is a tumor suppressor in solid tumors and myeloid leukemia [ 10 , 11 , 14 , 15 , 16 ]. However, a few studies have suggested that SSBP2 is a tumor promoter in glioblastoma and hepatocellular carcinoma [ 12 , 13 ].…”

Immunohistochemical Analysis of Single-Stranded DNA Binding Protein 2 in Non-Melanoma Skin Cancers

“…SSBP2-null mice showed an enhanced predisposition to malignancy [7], and SSBP2 was downregulated in prostate cancer and esophageal squamous cell carcinoma cell lines and inhibited tumor cell growth [8,9]. Low SSBP2 expression at the protein level has been linked to an aggressive phenotype and unfavorable prognosis in some types of solid tumors [10][11][12][13]. However, studies on glioblastoma with an SSBP2-inherited variant [14] and hepatocellular carcinoma [15] showed that high SSBP2 expression was associated with poor clinical outcomes, suggesting an oncogenic role of SSBP2.…”