Upregulation of transmembrane 4 L6 family member 1 predicts poor prognosis in invasive breast cancer: A STROBE-compliant article

Abstract

Transmembrane 4 L6 family member 1 (TM4SF1) belongs to the 4-transmembrane-domain family and functions as an oncogene in multiple human cancers. In this work, we aim to determine TM4SF1 expression and its prognostic impact on patients with invasive breast cancer.Overall, we enrolled 209 invasive breast cancer patients and immunohistochemically examined the expression of TM4SF1 in tumor specimens. The relationship between TM4SF1 expression and clinicopathological parameter and patient survival of breast cancer patients was analyzed.Among the 209 cases, 137 (65.6%) exhibited high expression of TM4SF1. High TM4SF1 expression was significantly associated with advanced histological grade and negative estrogen receptor and progesterone receptor status. Triple-negative breast cancer (TNBC) tumors were more likely to express high levels of TM4SF1 than non-TNBC cases. Patients with high tumoral expression of TM4SF1 had a significantly shorter disease-free survival (DFS; P = .00) and overall survival (OS; P = .01) than those with low expression of TM4SF1. When survival analysis was restricted to the 167 patients (79.9%) receiving adjuvant chemotherapy, TM4SF1 expression was also correlated with poorer DFS and OS (P = .00). In multiple Cox regression analysis TM4SF1 expression remained an independent prognostic indicator for OS and DFS.TM4SF1 is upregulated and serves as an independent poor prognostic indicator in invasive breast cancer.

Figure 1

Immunohistochemical analysis of TM4SF1 in breast cancer tissues and normal breast tissues. TM4SF1 showed membranous and cytoplasmic staining. Representative images of sections with different immunostaining intensity. Upper panels: 100×; lower panels: 200×.

Figure 2

Kaplan-Meier analysis of disease-free survival and overall survival in different cohorts of patients according to TM4SF1 expression status. A, Survival analysis in all the 209 breast cancer patients. B, Survival analysis in a subset of TNBC patients (n = 78). C, Survival analysis in a subset of patients receiving adjuvant chemotherapy (n = 167). Differences were determined using the Log-rank test.