Clinicopathological significance and prognostic value of cancer-associated fibroblasts in prostate cancer patients

Wu, Zhenyu; Shi, Juan; Lai, Cong; Li, Kaiwen; Li, Kuiqing; Li, Zhuohang; Tang, Zhuang; Liu, Cheng; Xu, Kecheng

doi:10.1016/j.urolonc.2021.05.004

Cited by 14 publications

(14 citation statements)

References 39 publications

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“…CAFs play an essential role in matrix remodelling and influence other processes in the tumour microenvironment, including angiogenesis, immunosuppression and invasion [8]. Wu et al [9] found that a high density of CAFs might be associated with a higher Gleason score and poor BCR free survival in PCa, which was similar to our findings. CAFs could originate from different tissues through a number of different cellular processes, including resident fibroblasts via transforming growth factor-β activation and epithelial and endothelial cells through the epithelial-to-mesenchymal transition and endothelial-tomesenchymal transition, respectively [10].…”

supporting

confidence: 90%

Cellular landscape of tumour microenvironment in prostate cancer

et al. 2022

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supporting

confidence: 90%

Cellular landscape of tumour microenvironment in prostate cancer

et al. 2022

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“…Numerous previous researches identified various mechanisms of CAFs tumor-promoting functions. Clinically, it was confirmed that the infiltration of activated CAFs was closely related to worse prognosis, resistance to multiple therapies, and even disease recurrence in cancer patients [416][417][418][419][420]. Hence, targeting CAFs has evolved as one of the appealing strategies for cancer intervention and is expected to provide oncologists with clinical decisionmaking (Table 3).…”

Section: Targeting Cafs For Cancer Therapymentioning

confidence: 90%

Targeting the tumor stroma for cancer therapy

Zhang

Xia

et al. 2022

Mol Cancer

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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

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“…Moreover, in cancer stroma, CAFs, as the main component, can induce a cancerous phenotype and support tumor epithelial growth, invasion, and therapeutic resistance ( Tripathi et al, 2012 ). The previous study showed that high density of CAFs might be associated with advanced-stage disease, higher Gleason scores, lymphatic metastases, higher PSA, and poor BCR-free survival in PCa patients ( Wu et al, 2021 ). Besides, prostatic CAFs could induce tumorigenesis in normal human prostatic epithelial cells in vitro via the secretion of CXCL12, and this mechanism was found to be dependent on the presence of TGF-β in vivo in a mouse model ( Fiard et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A Ferroptosis-Related Gene Prognostic Index Associated With Biochemical Recurrence and Radiation Resistance for Patients With Prostate Cancer Undergoing Radical Radiotherapy

Feng

Shi

Xiong

et al. 2022

Front. Cell Dev. Biol.

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Background: Ferroptosis is a new type of programmed cell death which has been reported to be involved in the development of various cancers. In this study, we attempted to explore the possible links between ferroptosis and prostate cancer (PCa), and a novel ferroptosis-related gene prognostic index (FGPI) was constructed to predict biochemical recurrence (BCR) and radiation resistance for PCa patients undergoing radical radiotherapy (RRT). Moreover, the tumor immune microenvironment (TME) of PCa was analyzed.Methods: We merged four GEO datasets by removing batch effects. All analyses were conducted with R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcriptional factor and competing endogenous RNA.Results: We established the FGPI based on ACSL3 and EPAS1. We observed that FGPI was an independent risk factor of BCR for PCa patients (HR: 3.03; 95% CI: 1.68–5.48), consistent with the result of internal validation (HR: 3.44; 95% CI: 1.68–7.05). Furthermore, FGPI showed high ability to identify radiation resistance (AUC: 0.963; 95% CI: 0.882–1.00). LncRNA PART1 was significantly associated with BCR and might modulate the mRNA expression of EPAS1 and ACSL3 through interactions with 60 miRNAs. Gene set enrichment analysis indicated that FGPI was enriched in epithelial–mesenchymal transition, allograft rejection, TGF beta signaling pathway, and ECM receptor interaction. Immune checkpoint and m6A analyses showed that PD-L2, CD96, and METTL14 were differentially expressed between BCR and no BCR groups, among which CD96 was significantly associated with BCR-free survival (HR: 1.79; 95% CI: 1.06–3.03). We observed that cancer-related fibroblasts (CAFs), macrophages, stromal score, immune score, estimate score, and tumor purity were differentially expressed between BCR and no BCR groups and closely related to BCR-free survival (HRs were 2.17, 1.79, 2.20, 1.93, 1.92, and 0.52 for cancer-related fibroblasts, macrophages, stromal score, immune score, estimate score, and tumor purity, respectively). Moreover, cancer-related fibroblasts (coefficient: 0.20), stromal score (coefficient: 0.14), immune score (coefficient: 0.14), estimate score (coefficient: 0.15), and tumor purity (coefficient: −0.15) were significantly related to FGPI, among which higher positive correlation between cancer-related fibroblasts and FGPI was observed.Conclusion: We found that FGPI based on ACSL3 and EPAS1 might be used to predict BCR and radiation resistance for PCa patients. CD96 and PD-L2 might be a possible target for drug action. Besides, we highlighted the importance of immune evasion in the process of BCR.

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Clinicopathological significance and prognostic value of cancer-associated fibroblasts in prostate cancer patients

Cited by 14 publications

References 39 publications

Cellular landscape of tumour microenvironment in prostate cancer

Cellular landscape of tumour microenvironment in prostate cancer

Targeting the tumor stroma for cancer therapy

A Ferroptosis-Related Gene Prognostic Index Associated With Biochemical Recurrence and Radiation Resistance for Patients With Prostate Cancer Undergoing Radical Radiotherapy

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