Abstract
Stem cell antigen-1 (Sca-1) is used to isolate and characterize tumor initiating cell populations from tumors of various murine models [1]. Sca-1 induced disruption of TGF-β signaling is required in vivo tumorigenesis in breast cancer models [2, 3-5]. The role of human Ly6 gene family is only beginning to be appreciated in recent literature [6-9]. To study the significance of Ly6 gene family members, we have visualized one hundred thirty gene expression omnibus (GEO) dataset using Oncomine (Invitrogen) and Georgetown Database of Cancer (G-DOC). This analysis showed that four different members Ly6D, Ly6E, Ly6H or Ly6K have increased gene expressed in bladder, brain and CNS, breast, colorectal, cervical, ovarian, lung, head and neck, pancreatic and prostate cancer than their normal counter part tissues. Increased expression of Ly6D, Ly6E, Ly6H or Ly6K was observed in sub-set of cancer type. The increased expression of Ly6D, Ly6E, Ly6H and Ly6K was found to be associated with poor outcome in ovarian, colorectal, gastric, breast, lung, bladder or brain and CNS as observed by KM plotter and PROGgeneV2 platform. The remarkable findings of increased expression of Ly6 family members and its positive correlation with poor outcome on patient survival in multiple cancer type indicate that Ly6 family members Ly6D, Ly6E, Ly6K and Ly6H will be an important targets in clinical practice as marker of poor prognosis and for developing novel therapeutics in multiple cancer type.
Highlights
The lymphocyte antigen-6 (Ly6) complex, a group of alloantigens, was first discovered in mice approximately 40 years ago on lymphocytes [3, 4]
The remarkable findings of increased expression of Ly6 family members and its positive correlation with poor outcome on patient survival in multiple cancer type indicate that Ly6 family members Ly6D, Ly6E, Ly6K and Ly6H will be an important targets in clinical practice as marker of poor prognosis and for developing novel therapeutics in multiple cancer type
We have previously shown that increased levels of Ly6A/E (Sca-1) promote breast tumorigenesis via disruption of TGF-β signaling and suppression of GDF10 expression in mouse models [2]
Summary
The lymphocyte antigen-6 (Ly6) complex, a group of alloantigens, was first discovered in mice approximately 40 years ago on lymphocytes [3, 4]. The founding Ly6 member CD59 was identified in human lymphoid cells with a role in the complement membrane attack complex and T cell activation [11]. Ly6 family is located on chromosome 8q24 alongside c-Myc. The somatic copy number gain in 8q has been associated with most prevalent copy number gain in multiple cancer types [12, 13]. GDF10 has been shown to regulate epithelial to mesenchymal transition, growth and invasion in oral squamous cell carcinoma [16]. These finding suggest that Ly6 genes family members have important role multiple cancer but a comprehensive analysis of multiple members www.impactjournals.com/oncotarget of Ly6 gene family and its relation to cancer patient survival is lacking
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