Cellular landscape of tumour microenvironment in prostate cancer

Feng, Dechao; Xiong, Qiao; Wei, Qiang; Yang, Lu

doi:10.1111/imm.13456

Cited by 21 publications

(17 citation statements)

References 14 publications

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“…CAFs, as the most important stromal cells, mediate ECM deposition and remodeling in the reactive stroma and increase tissue stiffness and induce mechanical stress [ 10 ]. Prostatic CAFs could induce tumorigenesis in normal human prostatic epithelial cell 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, which was consistent with our findings [ 11 , 12 ].…”

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confidence: 92%

Immune-related gene index predicts metastasis for prostate cancer patients undergoing radical radiotherapy

et al. 2023

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In this study, we established a novel immunologic gene prognostic index (IGPI) to predict metastasis and provided new insights into tumor immune microenvironment (TIME) for PCa patients receiving radical radiotherapy. GBP2 and IGF1 were independent factors associated with metastasis-free survival. IGPI score was calculated based on GBP2 and IGF1 and this score was an independent risk factor for PCa patients undergoing radical radiotherapy. Patients with higher IGPI score were at higher risk of metastasis and biochemical recurrence, which were externally validated in the TCGA database and other GEO datasets. IGPI score had demonstrated moderate diagnostic ability of radiation resistance (AUC: 0.889). This score increased with the augment of Gleason score and T stage, as well as biochemical recurrence. Using EPIC, ESTIMATE and immunophenoscore (IPS) algorithms, cancer associated fibroblasts (CAFs), macrophages, stromal score, and estimate score were significantly higher in patients with metastasis group compared to their counterpart. Besides, for CAFs, macrophages, stromal score, and estimate score, patients with higher scores were at higher risk of metastasis, and the HRs were 3.65, 4.01, 4.27, and 3.78, respectively. IGPI score was highly positively associated with stromal score (coefficient: 0.39), immune score (coefficient: 0.43), estimate score (coefficient: 0.45), CAFs (coefficient: 0.42) and macrophages (coefficient: 0.42), while showing the opposite relationship with tumor purity (coefficient: − 0.45). In conclusion, we found that IGPI based on GBP2 and IGF1 might serve as a biomarker predicting metastasis for PCa patients. Besides, the current data further highlight the importance of CAFs in the metastatic process of PCa.

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confidence: 92%

Immune-related gene index predicts metastasis for prostate cancer patients undergoing radical radiotherapy

et al. 2023

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“…Accumulative evidence have showed that, immune microenvironment is significantly associated with tumor prognosis[ 42 , 43 ]. Immune cell infiltration is considered to be an indicator of the immune microenvironment within tumors [ 44 – 46 ]. We report herein for the first time a statistical association between ORC6 expression level and immune cell infiltration.…”

Section: Discussionmentioning

confidence: 99%

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis

et al. 2023

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Background The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated. Methods In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases. Results ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6. Conclusions This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.

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“…PCA has been shown to be one of the most heritable cancers, with up to 57% heritable aetiology, and consist of manifold frequent and a few rare germline genetic variants [9,10]. The differences in the aetiology and clinical behaviour can be partially attributed to genetic heterogeneity [11]. Immunotherapy has been an important concept in the study of PCA, which might improve the treatment strategies and the quality of life of PCA patients [12].…”

Section: Introductionmentioning

confidence: 99%

Developing an immune‐related gene prognostic index associated with progression and providing new insights into the tumor immune microenvironment of prostate cancer

Feng

Zhang

et al. 2022

Immunology

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We developed an immune‐related gene prognostic index (IGPI) associated with progression and provided new insights into the tumour immune microenvironment (TIME) for prostate cancer (PCA) patients undergoing radical prostatectomy. All analyses were conducted with R software (version 3.6.3) and its suitable packages. Meta‐analysis was performed with STATA 16.0. TUBB3, WDR62 and PPARGC1A were finally identified to establish the IGPI score. The IGPI score increased with the augment of the Gleason score and T stage, as well as biochemical recurrence (BCR) and prostate specific antigen (PSA). Patients with a higher IGPI score were at a higher risk of progress (HR: 2·88; 95%CI: 95%CI: 1·80–4·61). Gene set enrichment analysis indicated that patients in high‐risk group were positively associated with mismatch repair, cell cycle, DNA replication, base excision repair, nucleotide excision repair, homologous recombination and pyrimidine metabolism. We observed that patients in the high‐risk group had significantly higher tumour mutation burden score and microsatellite instability score than those in the low‐risk group. For analysis of immune checkpoint, ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 were differentially expressed between no progress and progress groups and were significantly associated with progress free survival. We observed positive correlations between the IGPI score and lymphoid immune cells, macrophages M2 and immune score, while negative association between the IGPI score and dendritic cells, fibroblasts, stromal score and microenvironment score. In conclusion, the IGPI score constructed in this study might serve as an independent risk factor associated with PCA progression. ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 might be the potential targets in the treatment of PCA.

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Cellular landscape of tumour microenvironment in prostate cancer

Abstract: Prostate cancer is still a public health priority in men and the impact of this disease will be more pronounced with the ageing of the world's population. Clinical

Cited by 21 publications

References 14 publications

Immune-related gene index predicts metastasis for prostate cancer patients undergoing radical radiotherapy

Immune-related gene index predicts metastasis for prostate cancer patients undergoing radical radiotherapy

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis

Developing an immune‐related gene prognostic index associated with progression and providing new insights into the tumor immune microenvironment of prostate cancer

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