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// Linlin Luo 1, 3 , Peter McGarvey 1, 3 , Subha Madhavan 1, 3 , Rakesh Kumar 2 , Yuriy Gusev 1, 3 , Geeta Upadhyay 1, 3 1 Innovation Center for Biomedical Informatics (ICBI), Georgetown University Medical Center, Washington, District of Columbia 20007, United States of America 2 Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, District of Columbia 20037, United States of America 3 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20007, United States of America Correspondence to: Geeta Upadhyay, e-mail: geeta.upadhyay@georgetown.edu Keywords: cancer biomarkers, stem cell genes, poor prognosis, lymphocyte antigens 6 complex, Ly6 genes Received: October 07, 2015 Accepted: January 23, 2016 Published: February 03, 2016 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.