Evidence map›Paper›PMID 31285951›Full record

ArticleAmerican journal of cancer research2019

Genome-scale CRISPR activation screening identifies a role of ELAVL2-CDKN1A axis in paclitaxel resistance in esophageal squamous cell carcinoma.

Wen-Si Zhao, Wan-Pu Yan, Dong-Bo Chen, Liang Dai, Yong-Bo Yang, Xiao-Zheng Kang, Hao Fu, Pu Chen, Kang-Jian Deng, Xue-Yan Wang and 3 more

Abstract read
In one paragraph

Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
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

23 citing papers in PubMed.

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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

13 authors.

Wen-Si ZhaoDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Wan-Pu YanDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Dong-Bo ChenPeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Liang DaiDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Yong-Bo YangDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Xiao-Zheng KangDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Hao FuDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.
Pu ChenPeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Kang-Jian DengPeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Xue-Yan WangPeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Xing-Wang XiePeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Hong-Song ChenPeking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Disease Beijing 100044, China.
Ke-Neng ChenDepartment of Thoracic Surgery I, Peking University Cancer Hospital and Institute Beijing 100142, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neoadjuvant chemotherapy (NAC) may provide survival benefits for patients with advanced esophageal squamous cell carcinoma. However, tumor cells can display primary or secondary resistance to paclitaxel (PTX), a primary component of induction chemotherapy regimen. To identify genes capable of conveying PTX resistance, we performed a genome-wide CRISPR transcriptional activation library in human KYSE-180 cells. High throughput next generation sequencing was further applied to establish the phenotype-to-genotype relationship. Our highest-ranking hits are CDKN1A, TSPAN4, ELAVL2, JUNB and PAAF1. We generated evidence that esophageal tumors with high CDKN1A, ELAVL2 and TSPAN4 levels, quantified using qRT-PCR and Western blot assays, showed poorer chemotherapy response. Higher expression levels of TSPAN4 and ELAVL2 protein are independent risk factors for poor chemotherapy response in ESCC patients. We then found that overexpression of CDKN1A, ELAVL2 or TSPAN4 in ESCC cell lines significantly promoted the resistance to PTX by inhibiting cell apoptosis. Interestingly, ESCC cells overexpressed CDKN1A, ELAVL2 or TSPAN4 also acquired resistance to cisplatin (DDP). This phenomenon may be explained by cross-resistance of chemotherapy. We additionally found an association between ELAVL2 and CDKN1A, which may be regarded as the upstream and downstream factors that synergistically involved in the regulation of chemo-resistance in ESCC. Therefore, our study demonstrated that the genome-wide CRISPR activation library is a powerful strategy for the discovery of chemo-resistant genes critical for ESCC and we reported the first evidence that the ELAVL2-CDKN1A axis may be an important mechanism involved in chemo-resistance in ESCC.

Indexed as

CRISPR librarydrug-resistant genesEsophageal squamous cell carcinomahigh throughputneoadjuvant chemotherapy

Identifiers

PMID31285951
PMCPMC6610048

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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.