A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

Ren, Qianhe; Zhang, Pengpeng; Zhang, Xiao; Feng, Yanlong; Li, L; Lin, Haoran; Yu, Yue

doi:10.3389/fimmu.2023.1199040

Cited by 23 publications

(10 citation statements)

References 53 publications

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“…These approaches span from the analysis of cancer cell intrinsic features, such as the presence of specific gene mutations and their metabolic status, to the characterization of tumor associated stroma cells ( 169 – 172 ). Indeed, CAFs represent not only a promising prognostic biomarker ( 173 , 174 ), but may also grant the possibility to predict ICIs efficacy, as highlighted in the present work. In this scenario, the ECM and its remodeling are entangled with the CAFs function and represent a passepartout to unravel the traits of the tumor immune environment.…”

Section: Discussionmentioning

confidence: 62%

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Fejza,

Carobolante,

Poletto

et al. 2023

Front. Immunol.

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IntroductionImmune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs’ efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches.MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool.ResultsAfter employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs.ConclusionECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.

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Section: Discussionmentioning

confidence: 62%

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Fejza,

Carobolante,

Poletto

et al. 2023

Front. Immunol.

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“…The CHN2 gene encodes a GTP-metabolizing protein crucial for cell proliferation and migration. The F2RL2 gene showed a significant correlation with colorectal cancer initiation and progression in a prior study [ 25 ]. PDPK1 has been implicated in treatment resistance and cancer cell growth across several cancer types [ 26 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

Unveiling Prognostic RNA Biomarkers through a Multi-Cohort Study in Colorectal Cancer

Kim,

Lee,

Yoon

et al. 2024

IJMS

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Because cancer is a leading cause of death and is thought to be caused by genetic errors or genomic instability in many circumstances, there have been studies exploring cancer’s genetic basis using microarray and RNA-seq methods, linking gene expression data to patient survival. This research introduces a methodological framework, combining heterogeneous gene expression data, random forest selection, and pathway analysis, alongside clinical information and Cox regression analysis, to discover prognostic biomarkers. Heterogeneous gene expression data for colorectal cancer were collected from TCGA-COAD (RNA-seq), and GSE17536 and GSE39582 (microarray), and were integrated with Entrez Gene IDs. Using Cox regression analysis and random forest, genes with consistent hazard ratios and significantly affecting patient survivability were chosen. Predictive accuracy was evaluated using ROC curves. Pathway analysis identified potential RNA biomarkers. The authors identified 28 RNA biomarkers. Pathway analysis revealed enrichment in cancer-related pathways, notably EGFR downstream signaling and IGF1R signaling. Three RNA biomarkers (ZEB1-AS1, PI4K2A, and ITGB8-AS1) and two clinical biomarkers (stage and age) were chosen for a prognostic model, improving predictive performance compared to using clinical biomarkers alone. Despite biomarker identification challenges, this study underscores integration of heterogenous gene expression data for discovery.

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“…Esophageal cancer (EC), ranking 8th in incidence and 6th in mortality globally, poses a severe risk. With the current incidence rates, an estimated 957,000 new cases of EC are projected by 2040 ( 1 , 27 , 28 ). Unfortunately, many patients are diagnosed at advanced stages, leading to dismal 5-year survival rates ( 2 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy

Li,

Song,

Zhang

et al. 2023

Front. Immunol.

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BackgroundEsophageal squamous cell carcinoma (ESCC), characterized by its high invasiveness and malignant potential, has long been a formidable challenge in terms of treatment.MethodsA variety of advanced analytical techniques are employed, including single-cell RNA sequencing (scRNA-seq), cell trajectory inference, transcription factor regulatory network analysis, GSVA enrichment analysis, mutation profile construction, and the inference of potential immunotherapeutic drugs. The purpose is to conduct a more comprehensive exploration of the heterogeneity among malignant squamous epithelial cell subgroups within the ESCC microenvironment and establish a model for predicting the prognosis and immunotherapy outcomes of ESCC patients.ResultsAn analysis was conducted through scRNA-seq, and three Cluster of malignant epithelial cells were identified using the infer CNV method. Cluster 0 was found to exhibit high invasiveness, whereas Cluster 1 displayed prominent characteristics associated with epithelial-mesenchymal transition. Confirmation of these findings was provided through cell trajectory analysis, which positioned Cluster 0 at the initiation stage of development and Cluster 1 at the final developmental stage. The abundance of Cluster 0-2 groups in TCGA-LUAD samples was assessed using ssGSEA and subsequently categorized into high and low-expression groups. Notably, it was observed that Cluster 0-1 had a significant impact on survival (p<0.05). Furthermore, GSVA enrichment analysis demonstrated heightened activity in hallmark pathways for Cluster 0, whereas Cluster 1 exhibited notable enrichment in pathways related to cell proliferation. It is noteworthy that a prognostic model was established utilizing feature genes from Cluster 0-1, employing the Lasso and stepwise regression methods. The results revealed that in TCGA and GSE53624 cohorts, the low-risk group demonstrated significantly higher overall survival and increased levels of immune infiltration. An examination of four external immunotherapy cohorts unveiled that the low-risk group exhibited improved immunotherapeutic efficacy. Additionally, more meaningful treatment options were identified for the low-risk group.ConclusionThe findings revealed distinct interactions between malignant epithelial cells of ESCC and subgroups within the tumor microenvironment. Two cell clusters, strongly linked to survival, were pinpointed, and a signature was formulated. This signature is expected to play a crucial role in identifying and advancing precision medicine approaches for the treatment of ESCC.

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A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

Cited by 23 publications

References 53 publications

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Unveiling Prognostic RNA Biomarkers through a Multi-Cohort Study in Colorectal Cancer

Single-cell transcriptomics reveals heterogeneity in esophageal squamous epithelial cells and constructs models for predicting patient prognosis and immunotherapy

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