Evidence map›Paper›PMID 40775648›Full record

ArticleJournal of translational medicine2025

Integrative multiomics analysis reveals the subtypes and key mechanisms of platinum resistance in gastric cancer: identification of KLF9 as a promising therapeutic target.

Pengcheng Zhang, Lexin Wang, Haonan Lin, Yihui Han, Jingfang Zhou, Hang Song, Peng Wang, Huanhuan Tan, Yajuan Fu

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 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

9 authors.

Pengcheng Zhang *The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310002, China.
Lexin Wang *General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Haonan LinDepartment of Otolaryngology, Affiliated Hospital of Shaoxing University Shao Xing, Shaoxing, 312000, China.
Yihui HanDepartment of Clinical Medicine, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750000, Ningxia, China.
Jingfang ZhouDepartment of Clinical Medicine, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750000, Ningxia, China.
Hang SongSchool of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China. hangsong@ahtcm.edu.cn.
Peng WangDepartment of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. wisdom-wp@tmmu.edu.cn.
Huanhuan TanState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166, China.
Yajuan FuDepartment of Clinical Medicine, National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, 750000, Ningxia, China. 20210202@nxmu.edu.cn.

Funding

the open competition mechanism to select the best candidates for key research projects of Ningxia Medical University XJKF240313
6 · The paper itself

Abstract

backgroundGastric cancer (GC) is characterized by significant intertumoral heterogeneity, which often leads to the development of resistance to platinum-based chemotherapy. Combining platinum drugs with other therapeutic strategies may improve treatment efficacy; however, the mechanisms underlying platinum resistance in GC remain unclear.

methodsKey genes related to platinum resistance in GC were selected from the platinum resistance gene database and GC resistance datasets. The Similarity Network Fusion (SNF) algorithm was employed, along with prognosis-related methylation data and somatic mutation data, to classify the molecular subtypes of GC based on GC platinum resistance genes. Gene expression profiles, prognosis, immune cell infiltration, chemotherapy sensitivity, and immunotherapy responsiveness were comprehensively evaluated for each subtype. Localization and functional evaluation were conducted at the single-cell and spatial transcriptomics levels, and predictive models were developed using machine learning techniques. These functional differences in platinum resistance gene models were further explored in GC. Moreover, experimental validation was conducted to elucidate the mechanisms of key genes involved in platinum resistance in GC.

resultsStomach adenocarcinoma (STAD) patients were classified into three subtypes using the SNF algorithm and multiomics data. Patients with subtype CS2 exhibited a significantly poorer prognosis than those with subtypes CS1 and CS3 (p < 0.05). Subtype CS1 was characterized as immune-deprived, CS2 as stroma-enriched, and CS3 as immune-enriched. Patients with subtype CS2 also exhibited the most adverse therapeutic responses to docetaxel, cisplatin, and gemcitabine. Single-cell analysis revealed high enrichment of M1 module cells with elevated expression of resistance genes, including the transcription factor KLF9. Spatial transcriptomic analysis further confirmed the independent spatial distribution of malignant cells with high expression of drug resistance genes (DRGs). Predictive models based on machine learning demonstrated excellent prognostic performance. Patients in the high DRG group also exhibited poorer responses to immunotherapy. Cellular experiments revealed that KLF9 overexpression significantly inhibited the proliferation of AGS cells (p < 0.05), reduced their resistance to platinum-based drugs, and markedly decreased the levels of inflammatory cytokines in them.

conclusionKLF9 was identified as a promising therapeutic target for overcoming platinum resistance in GC, warranting further investigation into its role and potential clinical applications.

Indexed as

Drug Resistance, NeoplasmKruppel-Like Transcription FactorsMolecular Targeted TherapyPlatinumStomach NeoplasmsCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMultiomicsPrognosisReproducibility of ResultsKruppel-Like Transcription FactorsPlatinumGastric cancerKLF9Platinum resistanceSimilarity network fusionSpatial transcriptomics

Identifiers

PMID40775648
PMCPMC12330134

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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.