Evidence map›Paper›PMID 33058325›Full record

ArticleCancer science2021

Distinct roles of programmed death ligand 1 alternative splicing isoforms in colorectal cancer.

Chaoyan Wang, Menghan Weng, Shuli Xia, Min Zhang, Chaoyi Chen, Jinlong Tang, Dan Huang, Hongfei Yu, Wenjie Sun, Honghe Zhang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. PD-1Journal for immunotherapy of cancer · 2025
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  11. PD-L1: expression regulation.Blood science (Baltimore, Md.) · 2023
    Review
  12. Article
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  14. Review
  15. Article
  16. Article
  17. Article
  18. Role of immune escape in different digestive tumours.World journal of clinical cases · 2021
    Review
  19. Article
  20. Review
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

11 authors at 3 institutions in 1 country.

Chaoyan WangDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-2513-9178
Menghan WengDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Shuli XiaDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Min ZhangDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Chaoyi ChenDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Jinlong TangDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Dan HuangDepartment of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Hongfei YuDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Wenjie SunDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Honghe ZhangDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Maode LaiDepartment of Pathology, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of Chinese Academy of Medical Sciences (2019RU042), Zhejiang University School of Medicine, Hangzhou, China.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNChina Pharmaceutical University · CNFudan University Shanghai Cancer Center · CN

Funding

the 111 Project B13026the National Natural Science Foundation of China 81672730the National Natural Science Foundation of China 81871937the National Natural Science Foundation of China 82072629the National Natural Science Foundation of China 91859204
6 · The paper itself

Abstract

Although anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has achieved great success in some cancers, most colorectal cancer (CRC) patients remain unresponsive. Therefore, further clarification of the underlying mechanisms is needed to improve the therapy. In this study, we explored the distinct functions of different PD-L1 alternative splicing isoforms in CRC. We investigated the biological functions in PD-L1 knocked down/knockout cells, which were verified through overexpression of PD-L1 isoforms a, b, and c. The roles of PD-L1 isoforms in immune surveillance resistance was also analyzed. Meanwhile, we performed RNA-seq to screen the downstream molecules regulated by PD-L1 isoforms. Finally, we detected PD-L1 and PD-L1 isoforms levels in a cohort of serum samples, two cohorts of CRC tissue samples, and analyzed the correlation of PD-L1 isoforms with PD-1 blockade therapy response in two clinical CRC cases. The results indicated that PD-L1 knockout inhibited proliferation, migration, and invasion, and isoform b exerted a more significant inhibitory effect on T cells than the other two isoforms. Moreover, isoform c could promote CRC progression through regulating epithelial-mesenchymal transition. Clinical data showed that CRC patients with positive PD-L1 expression were associated with poorer overall survival. High serum PD-L1 level was associated with poor prognosis. The level of isoform b or c was negatively associated with prognosis, and a higher level of isoform b was associated with a good response to anti-PD-1 therapy. In conclusion, isoform b should be considered as a biomarker for clinical responsiveness to anti-PD-1/PD-L1 immunotherapy; isoform c had a prometastatic role and is a new potential target for CRC therapy.

Indexed as

Alternative SplicingAnimalsB7-H1 AntigenBiomarkers, TumorCell LineCell Line, TumorColorectal NeoplasmsEpithelial-Mesenchymal TransitionHCT116 CellsHT29 CellsHumansImmunotherapyMaleMiceMice, Inbred NODMice, NudeB7-H1 AntigenBiomarkers, TumorCD274 protein, humanProtein Isoformsalternative splicingcolorectal cancerimmunotherapyisoformPD-L1

Identifiers

PMID33058325
PMCPMC7780007
OpenAlexW3092722749

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Registered trials

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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.