Evidence map›Paper›PMID 40186284›Full record

ArticleCell communication and signaling : CCS2025

Machine learning-based in-silico analysis identifies signatures of lysyl oxidases for prognostic and therapeutic response prediction in cancer.

Qingyu Xu, Ling Ma, Alexander Streuer, Eva Altrock, Nanni Schmitt, Felicitas Rapp, Alessa Klär, Verena Nowak, Julia Obländer, Nadine Weimer and 6 more

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Collagen remodeling in breast cancer progression: from molecular mechanisms to diagnostic and therapeutic opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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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

16 authors.

Qingyu XuDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany. qingyuxu2@163.com.
Ling MaDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Alexander StreuerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Eva AltrockDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Nanni SchmittDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Felicitas RappDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Alessa KlärDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Verena NowakDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Julia ObländerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Nadine WeimerDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Iris PalmeDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Melda GölDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Hong-Hu ZhuDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Wolf-Karsten HofmannDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Daniel NowakDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.
Vladimir RiabovDepartment of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68169, Germany.

Funding

Beijing Chao-Yang Hospital Golden Seeds Foundation CYJZ202303National Natural Science Foundation of China 82400147National Natural Science Foundation of China 82450101, 82370169the Beijing Hospitals Authority "Dengfeng" talent training plan DFL20240301the German José-Carreras-Foundation DJCLSH03/01the "Phoenix" Project in Chaoyang District, Beijing Y2024070019
6 · The paper itself

Abstract

backgroundLysyl oxidases (LOX/LOXL1-4) are crucial for cancer progression, yet their transcriptional regulation, potential therapeutic targeting, prognostic value and involvement in immune regulation remain poorly understood. This study comprehensively evaluates LOX/LOXL expression in cancer and highlights cancer types where targeting these enzymes and developing LOX/LOXL-based prognostic models could have significant clinical relevance.

methodsWe assessed the association of LOX/LOXL expression with survival and drug sensitivity via analyzing public datasets (including bulk and single-cell RNA sequencing data of six datasets from Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA) and Cancer Genome Atlas Program (TCGA)). We performed comprehensive machine learning-based bioinformatics analyses, including unsupervised consensus clustering, a total of 10 machine-learning algorithms for prognostic prediction and the Connectivity map tool for drug sensitivity prediction.

resultsThe clinical significance of the LOX/LOXL family was evaluated across 33 cancer types. Overexpression of LOX/LOXL showed a strong correlation with tumor progression and poor survival, particularly in glioma. Therefore, we developed a novel prognostic model for glioma by integrating LOX/LOXL expression and its co-expressed genes. This model was highly predictive for overall survival in glioma patients, indicating significant clinical utility in prognostic assessment. Furthermore, our analysis uncovered a distinct LOXL2-overexpressing malignant cell population in recurrent glioma, characterized by activation of collagen, laminin, and semaphorin-3 pathways, along with enhanced epithelial-mesenchymal transition. Apart from glioma, our data revealed the role of LOXL3 overexpression in macrophages and in predicting the response to immune checkpoint blockade in bladder and renal cancers. Given the pro-tumor role of LOX/LOXL genes in most analyzed cancers, we identified potential therapeutic compounds, such as the VEGFR inhibitor cediranib, to target pan-LOX/LOXL overexpression in cancer.

conclusionsOur study provides novel insights into the potential value of LOX/LOXL in cancer pathogenesis and treatment, and particularly its prognostic significance in glioma.

Indexed as

Computer SimulationMachine LearningNeoplasmsProtein-Lysine 6-OxidaseComputational BiologyGene Expression Regulation, NeoplasticHumansPrognosisProtein-Lysine 6-OxidaseLysyl oxidasesMachine learningPan cancerPrognostic modelResponse prediction

Identifiers

PMID40186284
PMCPMC11971788

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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.