High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma

Abstract

Pancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A detailed study of mRNA expression of LY6 gene family and its association with overall survival (OS) outcome in pancreatic cancers is lacking. We used publicly available clinical datasets to analyze the mRNA expression of a set of LY6 genes and its effect on OS outcome in the context of the tumor microenvironment and immunomodulation. We used web-based tools Kaplan-Meier Plotter, cBioPortal, Oncomine and R-programming to analyze copy number alterations, mRNA expression and its association with OS outcome in pancreatic cancer. These analyses demonstrated that high expression of LY6 genes is associated with OS and disease free survival (DFS) outcome. High expression of LY6 genes and their association with OS outcome is dependent on the composition of tumor microenvironment. Considering that LY6 proteins are anchored to the outer cell membrane or secreted, making them readily accessible, these findings highlight the potential of LY6 family members in the future of pancreatic cancer diagnosis and treatment.

Human LY6 gene family: potential tumor-associated antigens and biomarkers of prognosis in uterine corpus endometrial carcinoma

“…Analyzing LY6 gene expression in a tumor may provide insight into a patient’s probability of survival or potential to respond to a certain therapy. Many LY6 genes have recently garnered attention for their potential role as biomarkers of poor patient prognosis in pancreatic ductal adenocarcinoma [ 3 ]. LY6K is especially of interest as high mRNA expression of this gene is associated with poor patient survival in thyroid, kidney, uterine, and esophageal carcinomas [ 25 ].…”

“…Negative and positive correlations between mRNA expression and overall survival were observed in other cancers as well. However, a focus was placed on UCEC since its LY6 gene expression pattern was most similar to that of pancreatic ductal adenocarcinoma, which has already been described [ 3 ].…”

“…The LY6 genes on chromosome 8q24.3 are of growing interest as this LY6 locus is frequently amplified in human cancer [ 3 ]. Genes located at this locus include LY6E, LY6L, LY6D, LY6K, LY6H, SLURP1, LYPD2, LYNX1, GML, and GPIHBP1 ; these genes are syntenic to mouse chromosome 15.…”

“…In total, the LY6 gene family is comprised of at least 26 members, which are located on chromosomes 6, 11, and 19, in addition to chromosome 8 [ 4 , 5 ]. Transcriptome analysis of pancreatic tumors has revealed upregulated expression of many LY6 genes when compared to normal pancreatic tissue [ 3 ]. These findings are consistent with previous reports that show an increased expression of PSCA and other LY6 genes (e.g., SLURP1 ) on a variety of neoplasms arising from prostate, bladder, ovarian, urothelial, and skin tissues [ 6 – 11 ].…”

MHC class III lymphocyte antigens 6 as endogenous immunotoxins: Unlocking immunotherapy in proficient mismatch repair colorectal cancer

“…Interestingly, unlike T cells, natural killer (NK) cells can lyse tumor cells independent of antigen presentation, based simply on their activation and inhibition receptors (Jhunjhunwala et al, 2021). High expression of LY6G6F and LY6G6D molecules in NK-low expression population is associated with poor overall survival outcome in patients with pancreatic cancer (Russ et al, 2021). It is likely that cell-cell interaction may play important role in deregulating LY6G signaling in cancer, but the reason for their uncontrolled expression is still unknown.…”