High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

Dai, Zao; Liu, Ping

doi:10.1186/s12967-021-02870-x

Cited by 12 publications

(12 citation statements)

References 70 publications

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“…It is widely accepted that replication stress plays a key role in initiating anti-tumor immunity by inducing cancer-related neoantigens ( 31 , 32 ), and its absence is intensively correlated with the immune desert phenotype. Consequently, the low immunity and high level of CNV can jointly contribute to strong cancer stemness ( 33 ), accounting for the result that patients of CS3 were tolerant of many ATR and week1 inhibitors in our study.…”

Section: Discussionmentioning

confidence: 67%

CAPN8 involves with exhausted, inflamed, and desert immune microenvironment to influence the metastasis of thyroid cancer

Xiang

Wang

et al. 2022

Front. Immunol.

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BackgroundThyroid cancer (THCA) is the most prevalent malignant disease of the endocrine system, in which 5-year survival can attain about 95%, but patients with metastasis have a poor prognosis. Very little is known about the role of CAPN8 in the metastasis of THCA. In particular, the effect of CAPN8 on the tumor immune microenvironment (TIME) and immunotherapy response is unclear.Material and methodsMultiome datasets and multiple cohorts were acquired for analysis. Firstly, the expression and the prognostic value of CAPN8 were explored in public datasets and in vitro tumor tissues. Then, hierarchical clustering analysis was performed to identify the immune subtypes of THCA according to the expression of CAPN8 and the activities of related pathways. Subsequent analyses explored the different patterns of TIME, genetic alteration, DNA replication stress, drug sensitivity, and immunotherapy response among the three immune phenotypes. Finally, five individual cohorts of thyroid cancer were utilized to test the robustness and extrapolation of the three immune clusters.ResultsCAPN8 was found to be a significant risk factor for THCA with a markedly elevated level of mRNA and protein in tumor tissues. This potential oncogene could induce the activation of epithelial–mesenchymal transition and E2F-targeted pathways. Three subtypes were identified for THCA, including immune exhausted, inflamed, and immune desert phenotypes. The exhausted type was characterized by a markedly increased expression of inhibitory receptors and infiltration of immune cells but was much more likely to respond to immunotherapy. The immune desert type was resistant to common chemotherapeutics with extensive genomic mutation and copy number variance.ConclusionThe present study firstly explored the role of CAPN8 in the metastasis of THCA from the aspects of TIME. Three immune subtypes were identified with quite different patterns of prognosis, immunotherapy response, and drug sensitivity, providing novel insights for the treatment of THCA and helping understand the cross-talk between CAPN8 and tumor immune microenvironment.

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Section: Discussionmentioning

confidence: 67%

CAPN8 involves with exhausted, inflamed, and desert immune microenvironment to influence the metastasis of thyroid cancer

Xiang

Wang

et al. 2022

Front. Immunol.

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“…Chen et al found that only an inflection point was observed in a few PCa samples, which can separate putative malignant cells from non-malignant cells in PCa. However, this distinction was not so precise in other samples [ 17 ], which may be because some localized PCa tumors have been shown to have a silent genome [ 20 ]. Furthermore, previous DNA sequencing studies have revealed that 0–50% of PCa genomes have CNAs and that CNAs are also a prognostic factor for PCa [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer

Xin

Liu

et al. 2023

Exp Hematol Oncol

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Background Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq. Methods A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed. Results The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence. Conclusions The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.

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“…This indicates that the high expression of this gene may cause breast cancer patients to have no immune response to the PD-1 antibody, which may be a prognostic marker of the PD-1 antibody. In addition, the copy number variation of the gene is also related to the infiltrating immune cells in the tumor tissue (37). There are fewer infiltrating immune cells in the tumor tissue with increased or decreased copy number, indicating that the copy number variation of the gene may affect the immune cell infiltration, which needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

et al. 2022

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BackgroundBreast cancer (BRCA) has become the most frequently appearing, lethal, and aggressive cancer with increasing morbidity and mortality. Previously, it was discovered that the HAUS5 protein is involved in centrosome integrity, spindle assembly, and the completion of the cytoplasmic division process during mitosis. By encouraging chromosome misdivision and aneuploidy, HAUS5 has the potential to cause cancer. The significance of HAUS5 in BRCA and the relationship between its expression and clinical outcomes or immune infiltration remains unclear.MethodsPan-cancer was analyzed by TIMER2 web and the expression differential of HAUS5 was discovered. The prognostic value of HAUS5 for BRCA was evaluated with KM plotter and confirmed with Gene Expression Omnibus (GEO) dataset. Following that, we looked at the relationship between the high and low expression groups of HAUS5 and breast cancer clinical indications. Signaling pathways linked to HAUS5 expression were discovered using Gene Set Enrichment Analysis (GSEA). The relative immune cell infiltrations of each sample were assessed using the CIBERSORT algorithm and ESTIMATE method. We evaluated the Tumor Mutation Burden (TMB) value between the two sets of samples with high and low HAUS5 expression, as well as the differences in gene mutations between the two groups. The proliferation changes of BRCA cells after knockdown of HAUS5 were evaluated by fluorescence cell counting and colony formation assay.ResultHAUS5 is strongly expressed in most malignancies, and distinct associations exist between HAUS5 and prognosis in BRCA patients. Upregulated HAUS5 was associated with poor clinicopathological characteristics such as tumor T stage, ER, PR, and HER2 status. mitotic prometaphase, primary immunodeficiency, DNA replication, cell cycle related signaling pathways were all enriched in the presence of elevated HAUS5 expression, according to GSEA analysis. The BRCA microenvironment’s core gene, HAUS5, was shown to be related with invading immune cell subtypes and tumor cell stemness. TMB in the HAUS5-low expression group was significantly higher than that in the high expression group. The mutation frequency of 15 genes was substantially different in the high expression group compared to the low expression group. BRCA cells’ capacity to proliferate was decreased when HAUS5 was knocked down.ConclusionThese findings show that HAUS5 is a positive regulator of BRCA progression that contributes to BRCA cells proliferation. As a result, HAUS5 might be a novel prognostic indicator and therapeutic target for BRCA patients.

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High copy number variations, particular transcription factors, and low immunity contribute to the stemness of prostate cancer cells

Cited by 12 publications

References 70 publications

CAPN8 involves with exhausted, inflamed, and desert immune microenvironment to influence the metastasis of thyroid cancer

CAPN8 involves with exhausted, inflamed, and desert immune microenvironment to influence the metastasis of thyroid cancer

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer

HAUS5 Is A Potential Prognostic Biomarker With Functional Significance in Breast Cancer

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