Upregulated immune checkpoint HHLA2 in clear cell renal cell carcinoma: a novel prognostic biomarker and potential therapeutic target

Chen, Dongming; Chen, Wei; Xu, Yong; Zhu, Meng; Xiao, Yi; Shen, Yanhao; Zhu, Shuai; Cao, Changchun; Xu, Xianlin

doi:10.1136/jmedgenet-2018-105454

Cited by 60 publications

(61 citation statements)

References 45 publications

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“…Previous studies have shown that HHLA2 is negatively expressed in most human tissues, whereas it is overexpressed in a variety of cancers [12]. High HHAL2 expression is associated with poor survival in patients with breast cancer, colon cancer, clear cell renal cell carcinoma, gastric cancer, or osteosarcoma [12,13,[16][17][18]. Consistently, in this study, we found that HHLA2 is upregulated in BUC tissues compared with normal tissues, and high HHLA2 expression predicts poor survival in BUC patients.…”

Section: Discussionsupporting

confidence: 77%

“…The widespread expression of HHLA2 indicates that HHLA2 probably plays a pivotal role in tumor development and progression [12]. Consistently, other studies showed that HHLA2 acts as a prognostic biomarker in several cancers, such as colorectal carcinoma, clear cell renal cell carcinoma, gastric cancer, and osteosarcoma [13,[16][17][18]. In non-small-cell lung carcinoma, HHLA2 expression is reported to be associated with EGFR mutation and high tumor-infiltrating lymphocyte density [19].…”

supporting

confidence: 51%

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Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Lin

Wang

et al. 2019

Nephron

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Background/Aims: human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is highly expressed in multiple solid malignant tumors, making it a potential biomarker for tumorigenesis and invasion. However, the expression and clinical significance of HHLA2 in bladder urothelial carcinoma (BUC) have not been extensively studied. This study aimed to investigate the relationship between HHLA2 expression and clinicopathological characteristics of BUC. Methods: A total of 212 patients pathologically diagnosed with BUC were included in this study. HHLA2 expression was analyzed by immunohistochemical staining and qRT-polymerase chain reaction. Correlations of HHLA2 expression and pathological characteristics, including 5-year recurrence-free survival (RFS) and overall survival (OS) were examined, and the diagnostic value of HHLA2 was estimated by using the receiver operating characteristic (ROC) curve. Results: Immunohistochemical staining showed that the expression of HHLA2 was significantly upregulated in BUC tissues compared with normal bladder tissues. In BUC tissues, HHLA2 expression was significantly associated with tumor size, tumor stage, tumor grade, and lymph node metastasis (all p < 0.05). HHLA2 expression was an independent prognostic factor of tumor metastasis (p < 0.05). The Kaplan-Meier survival curve revealed that high HHLA2 expression was significantly correlated with the poor RFS and OS of BUC patients (both p < 0.05), and the ROC curve showed HHLA2 could be a good diagnostic marker. Conclusions: HHLA2 can independently predict unfavorable prognosis in BUC.

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Section: Discussionsupporting

confidence: 77%

supporting

confidence: 51%

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Lin

Wang

et al. 2019

Nephron

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“…Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region . The incidence of OSCC accounts for more than 95% of oral malignant tumors and is still increasing worldwide . Meanwhile, OSCC is always characterized by invasive growth, frequent regional metastases of lymph nodes, high recurrence, and poor prognosis, accounting for the low living quality of patients .…”

Section: Introductionmentioning

confidence: 99%

“…Circular RNA (circRNA) is one kind of noncoding RNAs, characterized by a covalently closed loop, without a 5′cap or a 3′poly (A) tail, the structure of which account for its stability and resistance to RNA exonucleases. Increasing evidence showed that circRNAs are involved in various physiological and pathological processes, such as proliferation, apoptosis, invasion, differentiation, and aging . Recently, multiple circRNAs have been found to be the biomarkers of different diseases, especially cancers .…”

Section: Introductionmentioning

confidence: 99%

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma

Zhu

Shao

Tang

et al. 2019

J of Cellular Biochemistry

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Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real‐time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa‐miR‐933 overexpression. hsa_circRNA_100533 binds to hsa‐miR‐933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533‐miR‐933‐GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.

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“…As for immune checkpoint, Chen et al 28 evaluated the clinical significance of an immune inhibitory molecular called human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) in the prognosis and transcriptional regulatory network of clear cell renal cell carcinoma (ccRCC). They observed that HHLA2 expression was upregulated in ccRCC tumour tissue and its high expression leads to a remarkable shorter overall survival and poorer prognosis, indicating that HHLA2 might serve as a potential prognostic biomarker for ccRCC.…”

mentioning

confidence: 99%

Cancer immunotherapy: challenges and clinical applications

Xia¹,

2018

J Med Genet

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Upregulated immune checkpoint HHLA2 in clear cell renal cell carcinoma: a novel prognostic biomarker and potential therapeutic target

Abstract: Increased HHLA2 expression was observed in ccRCC tumour tissue, which leads to a remarkable shorter overall survival and poorer prognosis. Together with other molecular evidence, we have demonstrated that HHLA2 could be a potential prognostic biomarker for ccRCC.

Cited by 60 publications

References 45 publications

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma

Cancer immunotherapy: challenges and clinical applications

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