Barrier-to-autointegration factor 1: A novel biomarker for gastric cancer

Abstract

China is a country with a high incidence of gastric cancer (GC), where the GC incidence and the resultant mortality rates account for 50% of those worldwide. Surgical resection remains the primary treatment for GC. However, postoperative patients have a poor prognosis as the majority of patients present with metastases at the time of diagnosis. Therefore, the identification of novel treatment targets is required. The present study aimed to determine the effects of barrier-to-autointegration factor 1 (BANF1) on the clinical features and prognosis of GC, which may aid in discovering a novel tumor diagnostic biomarker and treatment target. The BANF1 gene expression profiles for normal and gastric tumor tissues were downloaded from the Gene Expression Omnibus GSE54129 data set to analyse the expression of BANF1 at the mRNA levels. Then, online survival analysis was performed using the GC database with the Kaplan-Meier Plotter (http://kmplot.com/analysis/) data. To examine the association between BANF1 and clinical features and prognosis, 132 postoperative GC pathological specimens were collected for immunohistochemical analyses. In the GSE54129 data sets, BANF1 expression at the mRNA level was significantly higher in the tumor tissue compared with that in the normal tissue. The same result was obtained in following the immunohistochemical analyses. In addition, BANF1 expression was associated with the patient age, tumor differentiation and infiltration depth. The survival time of BANF1 high-expression patients was shorter compared with that of the low-expression patients, and tumor differentiation status and tumor node metastasis stage were independent prognostic factors of the overall survival of patients with GC. The results of the present study suggest that BANF1 is associated with the clinical features and prognosis of GC. It may be a novel indicator of tumor prognosis and a potential therapeutic target for GC.

Keywords: barrier-to-autointegration factor 1; biomarker; clinical features; gastric cancer; prognosis.

Figure 1.

mRNA expression of BANF1 in the GSE54129 data sets. The gastric cancer microarray profiles were extracted from the Gene Expression Omnibus database under the accession number of GSE54129. BANF1 expression at the mRNA level in tumor tissues (10.05825) was significantly higher compared with that in normal tissues (6.93204) (P=1.50×10⁻⁸⁷). *P<0.05. BANF1, barrier-to-autointegration factor 1.

Figure 2.

Detection of BANF1 protein in SGC-7901 and MNK-45 gastric cancer cells by western blot analysis. Lanes 1, 3, 5 and 7 correspond to total cell extracts of SGC-7901 gastric cancer cells. Lanes 2, 4, 6 and 8 correspond to total cell extracts of MNK-45 gastric cancer cells. The diluted anti-BANF1 antibodies were preincubated with (+) and without (−) 0.5 mM anti-BANF1-peptide-specific antibodies. The positions of the BANF1 proteins are marked at 10 kDa in lanes 1 and 2, which were not present at the same position in lanes 3 and 4. BANF1, barrier-to-autointegration factor 1.

Figure 3.

Immunohistochemistry staining of BANF1 in gastric cancer. (A) Normal gastric tissues. (B) Atypical hyperplasia tissues. (C) Gastrointestinal stromal tumor tissues. (D) Poorly differentiated adenocarcinoma. (E) Moderately differentiated adenocarcinoma. (F) Highly differentiated adenocarcinoma. (A) No BANF1 expression (−); (F) weakly stained; (E) moderately positive expression (++) (C) and (D) strongly positive expression (+++) Magnification, ×200. BANF1, barrier-to-autointegration factor 1.

Figure 4.

Survival curve for patients with GC patients. (A) The K-M curve of BANF1 mRNA expression from the K-M Plotter data (log-rank test, P<1×10⁻¹⁶). (B) The K-M curve of BANF1 protein expression (log-rank test, P<0.001). The overall survival of the patients in the low-expression group was significantly improved compared with that of the patients in the high-expression group. BANF1, barrier-to-autointegration factor 1; Cum, cumulative; K-M, Kaplan-Meier.