Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC

Chen, Meng-Yu; Zeng, Yue‐Can; Zhao, Xihe

doi:10.3389/fcell.2022.893490

Cited by 4 publications

(4 citation statements)

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“…The alterations in the TIME have been demonstrated to play a crucial role in platinum resistance in various types of tumors (24)(25)(26). Tumor-associated macrophages (TAMs) are critical in tumor The relationship between the PRR scoring system and immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

Xiong,

Li,

Zeng

et al. 2023

Front. Immunol.

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ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients.

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Section: Discussionmentioning

confidence: 99%

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

Xiong,

Li,

Zeng

et al. 2023

Front. Immunol.

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“…Previous studies have reported human leukocyte antigen class II-based, chemotherapyand Immune-related, m6A regulatory expression-based, cisplatin resistance-related risk signatures in SCLC [46][47][48][49][50][51][52]. These studies constructed risk signatures based on genes associated with a particular pathway or treatment response.…”

Section: Discussionmentioning

confidence: 99%

A 15-Gene-Based Risk Signature for Predicting Overall Survival in SCLC Patients Who Have Undergone Surgical Resection

Atay

2023

Cancers

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Small cell lung cancer (SCLC) is a malignancy with a poor prognosis whose treatment has not progressed for decades. The survival benefit of surgery and the selection of surgical candidates are still controversial in SCLC. This study is the first report to identify transcriptomic alterations associated with prognosis and propose a gene expression-based risk signature that can be used to predict overall survival (OS) in SCLC patients who have undergone potentially curative surgery. An integrative transcriptome analysis of three gene expression datasets (GSE30219, GSE43346, and GSE149507) revealed 1734 up-regulated and 2907 down-regulated genes. Cox-Mantel test, Cox regression, and Lasso regression analyses were used to identify genes to be included in the risk signature. EGAD00001001244 and GSE60052-cohorts were used for internal and external validation, respectively. Overall survival was significantly poorer in patients with high-risk scores compared to the low-risk group. The discriminatory performance of the risk signature was superior to other parameters. Multivariate analysis showed that the risk signature has the potential to be an independent predictor of prognosis. The prognostic genes were enriched in pathways including regulation of transcription, cell cycle, cell metabolism, and angiogenesis. Determining the roles of the identified prognostic genes in the pathogenesis of SCLC may contribute to the development of new treatment strategies. The risk signature needs to be validated in a larger cohort of patients to test its usefulness in clinical decision-making.

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“…The progression of renal clear cell carcinoma (RCCC) is intricately linked to the immune system, with a particular emphasis on the distribution and function of T cells within the tumour microenvironment, exerting a direct influence on RCCC's growth and dissemination. [9][10][11] However, the heterogeneity within these T-cell populations remains a subject warranting more comprehensive exploration.…”

Section: Introductionmentioning

confidence: 99%

“…Precision medicine, when applied to renal clear cell carcinoma, signifies a tailored and efficacious treatment paradigm, with the potential to enhance both patient survival and quality of life. The progression of renal clear cell carcinoma (RCCC) is intricately linked to the immune system, with a particular emphasis on the distribution and function of T cells within the tumour microenvironment, exerting a direct influence on RCCC's growth and dissemination 9–11 . However, the heterogeneity within these T‐cell populations remains a subject warranting more comprehensive exploration.…”

Section: Introductionmentioning

confidence: 99%

Unravelling infiltrating T‐cell heterogeneity in kidney renal clear cell carcinoma: Integrative single‐cell and spatial transcriptomic profiling

Chen,

Zuo,

Huang

et al. 2024

J Cellular Molecular Medi

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Kidney renal clear cell carcinoma (KIRC) pathogenesis intricately involves immune system dynamics, particularly the role of T cells within the tumour microenvironment. Through a multifaceted approach encompassing single‐cell RNA sequencing, spatial transcriptome analysis and bulk transcriptome profiling, we systematically explored the contribution of infiltrating T cells to KIRC heterogeneity. Employing high‐density weighted gene co‐expression network analysis (hdWGCNA), module scoring and machine learning, we identified a distinct signature of infiltrating T cell‐associated genes (ITSGs). Spatial transcriptomic data were analysed using robust cell type decomposition (RCTD) to uncover spatial interactions. Further analyses included enrichment assessments, immune infiltration evaluations and drug susceptibility predictions. Experimental validation involved PCR experiments, CCK‐8 assays, plate cloning assays, wound‐healing assays and Transwell assays. Six subpopulations of infiltrating and proliferating T cells were identified in KIRC, with notable dynamics observed in mid‐ to late‐stage disease progression. Spatial analysis revealed significant correlations between T cells and epithelial cells across varying distances within the tumour microenvironment. The ITSG‐based prognostic model demonstrated robust predictive capabilities, implicating these genes in immune modulation and metabolic pathways and offering prognostic insights into drug sensitivity for 12 KIRC treatment agents. Experimental validation underscored the functional relevance of PPIB in KIRC cell proliferation, invasion and migration. Our study comprehensively characterizes infiltrating T‐cell heterogeneity in KIRC using single‐cell RNA sequencing and spatial transcriptome data. The stable prognostic model based on ITSGs unveils infiltrating T cells' prognostic potential, shedding light on the immune microenvironment and offering avenues for personalized treatment and immunotherapy.

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Chemotherapy- and Immune-Related Gene Panel in Prognosis Prediction and Immune Microenvironment of SCLC

Cited by 4 publications

References 49 publications

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB

A 15-Gene-Based Risk Signature for Predicting Overall Survival in SCLC Patients Who Have Undergone Surgical Resection

Unravelling infiltrating T‐cell heterogeneity in kidney renal clear cell carcinoma: Integrative single‐cell and spatial transcriptomic profiling

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