Evidence map›Paper›PMID 38762741›Full record

ArticleWorld journal of surgical oncology2024

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.

Siqi Zhou, Zhangding Wang, Dian Zhao, Yao Fu, Shu Zhang, Zhiping Wang, Xiaoping Zou

Abstract read
In one paragraph

Article in World journal of surgical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. 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

7 authors.

Siqi Zhou *Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China.
Zhangding Wang *Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Dian Zhao *State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
Yao FuDepartment of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Shu ZhangDepartment of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. zhangsgastro@nju.edu.cn.
Zhiping WangDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, No.99, Huaihai West Road, Xuzhou, 221000, China. zhpsqxt@163.com.
Xiaoping ZouDepartment of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. zouxp@nju.edu.cn.

Funding

National Natural Science Foundation of China 82270059Natural Science Foundation from the Department of Science and Technology of Jiangsu Province BK20221222
6 · The paper itself

Abstract

backgroundHuman endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated.

methodsWe initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored.

resultsSilencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs).

conclusionThe knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

Indexed as

Cell MovementCell ProliferationEpithelial-Mesenchymal TransitionErbB ReceptorsPancreatic NeoplasmsProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesApoptosisBiomarkers, TumorDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansImmunoglobulinsMacrophagesMaleBiomarkers, TumorEGFR protein, humanErbB ReceptorsHHLA2 protein, humanImmunoglobulinsMTOR protein, humanProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesHHLA2InvasionMigrationPancreatic cancerTumor-associated macrophages

Identifiers

PMID38762741
PMCPMC11102221

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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.