Upregulation of transmembrane 4 L6 family member 1 predicts poor prognosis in invasive breast cancer

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.

[1]  F. Du,et al.  SPARC overexpression in primary tumors correlates with disease recurrence and overall survival in patients with triple negative breast cancer , 2016, Oncotarget.

[2]  T. Arumugam,et al.  TM4SF1 Regulates Pancreatic Cancer Migration and Invasion In Vitro and In Vivo , 2016, Cellular Physiology and Biochemistry.

[3]  G. Jerusalem,et al.  Triple-negative breast cancer: treatment challenges and solutions , 2016, Breast cancer.

[4]  Fu Qiu,et al.  TM4SF1 Promotes Proliferation, Invasion, and Metastasis in Human Liver Cancer Cells , 2016, International journal of molecular sciences.

[5]  M. Patki,et al.  Role of the short isoform of the progesterone receptor in breast cancer cell invasiveness at estrogen and progesterone levels in the pre- and post-menopausal ranges , 2015, Oncotarget.

[6]  Yonghong Sun,et al.  Role of TM4SF1 in regulating breast cancer cell migration and apoptosis through PI3K/AKT/mTOR pathway. , 2015, International journal of clinical and experimental pathology.

[7]  T. Ohtsuka,et al.  TM4SF1 as a prognostic marker of pancreatic ductal adenocarcinoma is involved in migration and invasion of cancer cells. , 2015, International journal of oncology.

[8]  H. Cui,et al.  Transmembrane-4-L-six-family-1, a potential predictor for poor prognosis, overexpressed in human glioma , 2015, Neuroreport.

[9]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[10]  Kornelia Polyak,et al.  Heterogeneity in breast cancer. , 2011, The Journal of clinical investigation.

[11]  J. Samarut,et al.  TM4SF1, a novel primary androgen receptor target gene over‐expressed in human prostate cancer and involved in cell migration , 2011, The Prostate.

[12]  H. Dvorak,et al.  The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis. , 2009, Cancer research.

[13]  C. Perou,et al.  Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  F. Berditchevski,et al.  The tumour-associated antigen L6 (L6-Ag) is recruited to the tetraspanin-enriched microdomains: implication for tumour cell motility , 2008, Journal of Cell Science.

[15]  Pan‐Chyr Yang,et al.  CD13 (aminopeptidase N) can associate with tumor‐associated antigen L6 and enhance the motility of human lung cancer cells , 2005, International journal of cancer.

[16]  J. Shih,et al.  Tumor-associated antigen L6 and the invasion of human lung cancer cells. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  R. Broll,et al.  Diagnosis and Monitoring of Colorectal Cancer by L6 Blood Serum Polymerase Chain Reaction Is Superior to Carcinoembryonic Antigen–Enzyme-Linked Immunosorbent Assay , 2003, Diseases of the colon and rectum.

[18]  G. Schieven,et al.  Cloning and expression of the tumor-associated antigen L6. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[19]  H. Dvorak,et al.  The L 6 Protein TM 4 SF 1 Is Critical for Endothelial Cell Function and Tumor Angiogenesis , 2009 .

[20]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.