Evidence map›Paper›PMID 34217271›Full record

ArticleCancer cell international2021

Upregulation of ARNTL2 is associated with poor survival and immune infiltration in clear cell renal cell carcinoma.

Song Wang, Xueyou Ma, Yufan Ying, Jiazhu Sun, Zitong Yang, Jiangfeng Li, Ke Jin, Xiao Wang, Bo Xie, Xiangyi Zheng and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 26 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Song Wang *Department of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Xueyou Ma *Department of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Yufan Ying *Department of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Jiazhu SunDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Zitong YangDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Jiangfeng LiDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Ke JinDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Xiao WangDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Bo XieDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Xiangyi ZhengDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.
Ben LiuDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. drliuben@zju.edu.cn.ORCID http://orcid.org/0000-0002-0709-6784
Liping XieDepartment of Urology, School of Medicine, The First Affiliated Hospital, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China. xielp@zju.edu.cn.
First Affiliated Hospital Zhejiang University · CN

Funding

Medicine and Health Science and Technology Project of Zhejiang Province 2018KY032National Natural Science Foundation of China 81802564National Natural Science Foundation of China 81874203National Natural Science Foundation of China 81972374
6 · The paper itself

Abstract

backgroundAryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) is a member of the PAS superfamily. Previous studies explored the carcinogenic roles of transcription factor ARNTL2 in human malignancies. However, its roles in ccRCC have not been elucidated. This study sought to explore the roles of ARNTL2 in ccRCC and determine its correlations with tumor immunity.

methodsThe expression of ARNTL2 was analyzed using the GEO, TCGA and GTEx database, and verified in ccRCC tissue samples and cell lines by qRT-PCR and western blot analysis. Kaplan-Meier survival curve analysis, Cox regression analysis (including univariate and multivariate analysis) was utilized to evaluate the prognostic values of ARNTL2. Potential biological mechanisms of ARNTL2 were explored using GSEA method. Colony formation and wound healing assays were conducted to explore the oncogenic role of ARNTL2 in ccRCC. ssGSEA and xCell algorithm were used to explore the correlation between ARNTL2 expression and tumor immune microenvironment (TIME).

resultsARNTL2 was significantly upregulated in ccRCC tissues and cell lines compared to normal kidney tissues and cell line. Enhanced expression of ARNTL2 was strongly linked to advanced clinical stage and unfavorable overall survival in ccRCC. ARNTL2 was determined as an independent prognostic marker through cox regression analysis. A prognostic nomogram was constructed to predict 1-, 3- and 5-year overall survival of ccRCC patients by integrating ARNTL2 expression with other clinicopathologic variables. GSEA analysis showed that focal adhesion, T cell receptor, cell cycle, and JAK-STAT signaling pathway were significantly enriched in high ARNTL2 samples. Silencing of ARNTL2 suppressed the colony formation ability and wound healing efficacy of ccRCC cell lines. xCell analysis showed that high expression level of ARNTL2 exhibited an immune infiltration status similar to CD8 + inflamed ccRCC subtype, which was characterized by high infiltration level of CD8 + T cell and high expression level of the immune escape biomarkers such as PD-L1, PD-L2, PD1 and CTLA4.

conclusionARNTL2 is an independent adverse predictor of ccRCC patient survival. High expression level of ARNTL2 is associated with immune infiltration, and may be a novel therapeutic target in ccRCC.

Indexed as

ARNTL2Clear cell renal cell carcinomaImmune infiltrationUnfavorable survivalxCell

Identifiers

PMID34217271
PMCPMC8255002
OpenAlexW3178613235

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.