Evidence map›Paper›PMID 38824480›Full record

ArticleApoptosis : an international journal on programmed cell death2024

Integrated analysis reveals a novel 5-fluorouracil resistance-based prognostic signature with promising implications for predicting the efficacy of chemotherapy and immunotherapy in patients with colorectal cancer.

Yufang Hou, Fang Zhang, Jinbao Zong, Tiegang Li, Wenqiang Gan, Silin Lv, Zheng Yan, Zifan Zeng, Liu Yang, Mingxuan Zhou and 2 more

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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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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.

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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

12 authors.

Yufang Hou *State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Fang Zhang *State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Jinbao ZongClinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Tiegang LiState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Wenqiang GanState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Silin LvState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Zheng YanState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Zifan ZengState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Liu YangState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Mingxuan ZhouState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Wenyi ZhaoState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Min YangState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China. minyang@imm.ac.cn.

Funding

CAMS Innovation Fund for Medical Sciences (CIFMS) Grant 2023-I2M-2-009National Natural Science Foundation of China 81773750
6 · The paper itself

Abstract

background5-Fluorouracil (5-FU) has been used as a standard first-line treatment for colorectal cancer (CRC) patients. Although 5-FU-based chemotherapy and immune checkpoint blockade (ICB) have achieved success in treating CRC, drug resistance and low response rates remain substantial limitations. Thus, it is necessary to construct a 5-FU resistance-related signature (5-FRSig) to predict patient prognosis and identify ideal patients for chemotherapy and immunotherapy.

methodsUsing bulk and single-cell RNA sequencing data, we established and validated a novel 5-FRSig model using stepwise regression and multiple CRC cohorts and evaluated its associations with the prognosis, clinical features, immune status, immunotherapy, neoadjuvant therapy, and drug sensitivity of CRC patients through various bioinformatics algorithms. Unsupervised consensus clustering was performed to categorize the 5-FU resistance-related molecular subtypes of CRC. The expression levels of 5-FRSig, immune checkpoints, and immunoregulators were determined using quantitative real-time polymerase chain reaction (RT‒qPCR). Potential small-molecule agents were identified via Connectivity Map (CMap) and molecular docking.

resultsThe 5-FRSig and cluster were confirmed as independent prognostic factors in CRC, as patients in the low-risk group and Cluster 1 had a better prognosis. Notably, 5-FRSig was significantly associated with 5-FU sensitivity, chemotherapy response, immune cell infiltration, immunoreactivity phenotype, immunotherapy efficiency, and drug selection. We predicted 10 potential compounds that bind to the core targets of 5-FRSig with the highest affinity.

conclusionWe developed a valid 5-FRSig to predict the prognosis, chemotherapeutic response, and immune status of CRC patients, thus optimizing the therapeutic benefits of chemotherapy combined with immunotherapy, which can facilitate the development of personalized treatments and novel molecular targeted therapies for patients with CRC.

Indexed as

Colorectal NeoplasmsDrug Resistance, NeoplasmFluorouracilImmunotherapyBiomarkers, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMolecular Docking SimulationPrognosisBiomarkers, TumorFluorouracil5-fluorouracilChemotherapyColorectal cancerImmunotherapyPrognostic signatureTumor microenvironment

Identifiers

PMID38824480

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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.