Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

Zhou, Libin; Fang, Hualong; Yin, Min; Long, Huimin; Weng, Guobin

doi:10.1002/jcla.24409

Cited by 3 publications

(1 citation statement)

References 59 publications

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“…Previous reports have shown that TIMP3 is associated with the development of a variety of tumors [27,28]. In previous reports, we observed that TIMP3 showed high expression in pancreatic cancer tissues [29], and TIMP3 was upregulated in cervical cancer cell lines and cervical squamous cell carcinoma tissues. Shaker et al created a model in which they noted that the expression level of TIMP3 was increased in normal cervical cells during carcinogenesis as compared to parental HCK cells [30].…”

Section: Discussionmentioning

confidence: 57%

Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer

Ye,

Ding,

Zheng

2024

Preprint

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Purpose Ovarian cancer (OV) is a malignant gynecologic cancer with poor clinical outcomes and poor prognosis. The aim of this study was to explore the immune infiltration between primary and metastatic ovarian cancer and the function of fibroblast differential marker in ovarian cancer immunomodulation. Methods Obtained single-cell transcriptome datasets of primary ovarian cancer and metastatic ovarian cancer, performed cell communication analysis and enrichment analysis. Constructed a new fibroblast score, constructed a prognostic model, screened for prognostically relevant fibroblast differential markers, and analyzed the role of differential markers in immune infiltration of ligand-receptor cells. Results Single-cell data analysis of ovarian cancer revealed the existence of intercellular communication between fibroblasts and mononuclear macrophages. COX one-way analysis of 28 differential genes in ovarian cancer fibroblasts yielded five genes with prognostic significance for ovarian cancer, and a new Fib score constructed on the basis of these five genes accurately predicted the prognosis of ovarian cancer patients. Further analysis of these five genes revealed that TIMP3 in ovarian cancer fibroblasts affected tumor prognosis, immunosuppression, and drug resistance by targeting M2-type macrophages through the regulation of the CXCL12/CXCR4 signaling axis, which was specifically shown that the higher the expression of TIMP3, the worse the prognosis, the more significant the immune infiltration, and the more drug-resistant the ovarian cancer was. Conclusion In metastatic ovarian cancer, fibroblasts induce macrophage polarization through the TIMP3-regulated CXCL signaling pathway, which affects the prognosis of ovarian cancer patients and drug resistance of ovarian cancer cells.

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Section: Discussionmentioning

confidence: 57%

Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer

Ye,

Ding,

Zheng

2024

Preprint

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Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

Zhou

Fang

Yin

et al. 2022

Clinical Laboratory Analysis

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Background Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune‐related prognostic signature and investigate its relationship with immunotherapy response in ccRCC. Methods Immune‐related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan‐Meier analysis, PCA, t ‐SNE, and ROC were used to evaluate the risk model. Results A total of 119 immune‐related genes associated with prognosis were screened out. Six immune‐related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan–Meier analysis showed that patients in high‐risk group had a poorer survival outcome than in low‐risk group. The 1‐, 3‐ and 5‐year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high‐risk group was concentrated on immune‐related pathways. The high‐risk group with more regulatory T‐cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high‐risk group. Conclusion Our study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.

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Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma

Zhou,

Yin,

Guo

et al. 2024

Sci Rep

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Clear cell renal cell carcinoma (ccRCC) represents a highly frequent renal cancer subtype. However, medium-chain acyl-CoA dehydrogenase (ACADM) encodes an important enzyme responsible for fatty acid β-oxidation (FAO) and its association with prognosis and immunity in cancers has rarely been reported. Therefore, the present work focused on exploring ACADM’s expression and role among ccRCC cases. We used multiple public databases and showed the hypo levels of ACADM protein and mRNA within ccRCC. Additionally, we found that ACADM down-regulation showed a remarkable relation to the advanced stage, high histological grade, as well as dismal prognostic outcome. As suggested by Kaplan–Meier curve analysis, cases showing low ACADM levels displayed shorter overall survival (OS) as well as disease-free survival (DFS). Moreover, according to univariate/multivariate Cox regression, ACADM-mRNA independently predicted the prognosis of ccRCC. In addition, this work conducted immunohistochemistry for validating ACADM protein expression and its prognostic role in ccRCC samples. KEGG and GO analyses revealed significantly enriched genes related to ACADM expression during fatty acid metabolism. The low-ACADM group with more regulatory T-cell infiltration showed higher expression of immune negative regulation genes and higher TIDE scores, which might contribute to poor response to immunotherapies. In conclusion, our results confirmed that downregulated ACADM predicted a poor prognosis for ccRCC and a poor response to immunotherapy. Our results provide important data for developing immunotherapy for ccRCC.

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Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

Cited by 3 publications

References 59 publications

Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer

Single-cell transcriptomic construction of fibroblast score for analysis of immune infiltration in primary and metastatic ovarian cancer

Novel immune‐related signature based on immune cells for predicting prognosis and immunotherapy response in clear cell renal cell carcinoma

Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma

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