A narrative review of the emerging role of lymphocyte antigen 6 complex locus K in cancer: from basic research to clinical practice

Guo, Dandan; Liu, Yujia; Jiang, Yuchen; Zheng, Shuilian; Xu, Tong; Zhu, Jun; Chen, Pengcheng; Huang, Ping; Zhang, Yiwen

doi:10.21037/atm-21-5831

Cited by 6 publications

(4 citation statements)

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“…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 ]. Based on the results from these survival studies, we hypothesize that other LY6 genes may also serve as biomarkers of poor prognosis in different cancers.…”

Section: Resultsmentioning

confidence: 99%

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

Rathbun

Magliocco²,

Bamezai

2023

Oncotarget

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Section: Resultsmentioning

confidence: 99%

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

Rathbun

Magliocco²,

Bamezai

2023

Oncotarget

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“…Recently, knockdown of Ly6K expression in HeLa and SiHa cells inhibited proliferation induced by epidermal growth factor and suppressed migration and invasion stimulated by TGF-β signaling 54 . In addition, Ly6K has been used as a therapeutic target in several clinical trials 55 .…”

Section: Discussionmentioning

confidence: 99%

Aspartate β-hydroxylase Regulates Expression of Ly6 Genes

Kanwal,

Smahelova,

Ciharova

et al. 2024

J. Cancer

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Background: Overexpression of aspartate β-hydroxylase (ASPH) in human tumors contributes to their progression by stimulating cell proliferation, migration, and invasion. Several signaling pathways affected by ASPH have been identified, but the high number of potential targets of ASPH hydroxylation suggests that additional mechanisms may be involved. This study was performed to reveal new targets of ASPH signaling. Methods: The effect of ASPH on the oncogenicity of three mouse tumor cell lines was tested using proliferation assays, transwell assays, and spheroid invasion assays after inhibition of ASPH with the small molecule inhibitor MO-I-1151. ASPH was also deactivated with the CRISPR/Cas9 system. A transcriptomic analysis was then performed with bulk RNA sequencing and differential gene expression was evaluated. Expression data were verified by quantitative PCR and immunoblotting. Results: Inhibition or abrogation of ASPH reduced proliferation of the cell lines and their migration and invasiveness. Among the genes with differential expression in more than one cell line, two members of the lymphocyte antigen 6 ( Ly6 ) family, Ly6a and Ly6c1 , were found. Their downregulation was confirmed at the protein level by immunoblotting, which also showed their reduction after ASPH inhibition in other mouse cell lines. Reduced production of the Ly6D and Ly6K proteins was shown after ASPH inhibition in human tumor cell lines. Conclusions: Since increased expression of Ly6 genes is associated with the development and progression of both mouse and human tumors, these results suggest a novel mechanism of ASPH oncogenicity and support the utility of ASPH as a target for cancer therapy.

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“…Furthermore, we identified GULPsig, which includes IGF2BP1 , IGF2BP3 , SMC1B , CLDN6 , and LY6K , from these 42 genome instability-related genes. Each gene in GULPsig has been reported to be involved in tumor development ( Bell et al, 2013 ; Du et al, 2021 ; Nie et al, 2021 ; Guo D et al, 2022 ). We also constructed a risk model with GULPsig and stratified the patients into high- and low-risk groups based on the optimal cut-off threshold.…”

Section: Discussionmentioning

confidence: 99%

Genome instability-derived genes as a novel prognostic signature for lung adenocarcinoma

Zhang,

Lam,

Ting

2023

Front. Cell Dev. Biol.

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Background: An increasing number of patients are being diagnosed with lung adenocarcinoma, but there remains limited progress in enhancing prognostic outcomes and improving survival rates for these patients. Genome instability is considered a contributing factor, as it enables other hallmarks of cancer to acquire functional capabilities, thus allowing cancer cells to survive, proliferate, and disseminate. Despite the importance of genome instability in cancer development, few studies have explored the prognostic signature associated with genome instability for lung adenocarcinoma.Methods: In the study, we randomly divided 397 lung adenocarcinoma patients from The Cancer Genome Atlas database into a training group (n = 199) and a testing group (n = 198). By calculating the cumulative counts of genomic alterations for each patient in the training group, we distinguished the top 25% and bottom 25% of patients. We then compared their gene expressions to identify genome instability-related genes. Next, we used univariate and multivariate Cox regression analyses to identify the prognostic signature. We also performed the Kaplan–Meier survival analysis and the log-rank test to evaluate the performance of the identified prognostic signature. The performance of the signature was further validated in the testing group, in The Cancer Genome Atlas dataset, and in external datasets. We also conducted a time-dependent receiver operating characteristic analysis to compare our signature with established prognostic signatures to demonstrate its potential clinical value.Results: We identified GULPsig, which includes IGF2BP1, IGF2BP3, SMC1B, CLDN6, and LY6K, as a prognostic signature for lung adenocarcinoma patients from 42 genome instability-related genes. Based on the risk score of the risk model with GULPsig, we successfully stratified the patients into high- and low-risk groups according to the results of the Kaplan–Meier survival analysis and the log-rank test. We further validated the performance of GULPsig as an independent prognostic signature and observed that it outperformed established prognostic signatures.Conclusion: We provided new insights to explore the clinical application of genome instability and identified GULPsig as a potential prognostic signature for lung adenocarcinoma patients.

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A narrative review of the emerging role of lymphocyte antigen 6 complex locus K in cancer: from basic research to clinical practice

Cited by 6 publications

References 50 publications

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

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

Aspartate β-hydroxylase Regulates Expression of Ly6 Genes

Genome instability-derived genes as a novel prognostic signature for lung adenocarcinoma

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