Identification of new biomarkers in immune microenvironment of testicular germ cell tumour

Song, Yuxuan; Qi, Xiangjie; Kang, Jiaqi; Xiao, Wang; Ou, Ningjing; Jun, Zhu; Wang, Shangren; Liu, Xiaoqiang

doi:10.1111/and.13986

Cited by 8 publications

(11 citation statements)

References 51 publications

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“…These results show that SPA17 plays an essential role in predicting the prognosis of cancer patients and is expected to become a powerful biomarker of prognosis for cancer patients. Thus, some of our results are consistent with the conclusion of a previous study ( 32 ), making our results more reliable.…”

Section: Discussionsupporting

confidence: 93%

“…Notably, in TGCT, the SPA17 expression was significantly inhibited. This may be related to its ligand Ropporin, a spermatogenic cell-specific protein, which has also been confirmed in previous studies ( 31 , 32 ). The results indicated that SPA17 expression was unbalanced in cancers, consistent with previous studies.…”

Section: Resultssupporting

confidence: 86%

“…Many studies have suggested that SPA17 is closely related to the prognosis and progression of BRCA and TGCT ( 10 , 32 ). Therefore, we analyzed the Kaplan–Meier curve of BRCA and TGCT and found that a higher expression of SPA17 was related to a better survival outcome ( Figures 2C, F ) , indicating that SPA17 was a prognostic biomarker of OS in BRCA and TGCT.…”

Section: Resultsmentioning

confidence: 99%

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Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Peng

Long

et al. 2022

Front. Immunol.

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BackgroundSperm autoantigen protein 17 (SPA17) is a highly conserved mammalian protein that participates in the acrosome reaction during fertilization and is a recently reported member of the cancer-testicular antigen (CTA) family. It has been reported that the SPA17 expression is limited in adult somatic tissues and re-expressed in tumor tissues. Recently, studies have found that SPA17 regulates the progression of various cancers, but its role in cancer immunotherapy is not clear.MethodsThe pan-cancer and normal tissue transcriptional data were acquired from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) datasets. We explored the SPA17 pan-cancer genomic alteration analysis in the cBioPortal webtool. The Human Protein Atlas (HPA) and ComPPI websites were used to mine the SPA17 protein information. We performed a western blotting assay to validate the upregulated SPA17 expression in clinical glioblastoma (GBM) samples. The univariate Cox regression and Kaplan–Meier method were used to assess the prognostic role of SPA17 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was used to search the associated cancer hallmarks with SPA17 expression in each cancer type. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to SPA17 in pan-cancer. The associations between SPA17 and immunotherapy biomarkers were performed by Spearman correlation analysis. The drug sensitivity information from the Connectivity Map (CMap) dataset was downloaded to perform SAP17-specific inhibitor sensitivity analysis.FindingsSPA17 was aberrantly expressed in most cancer types and exhibited prognosis predictive ability in various cancers. In addition, our results also show that SPA17 was significantly correlated with immune-activated hallmarks (including pathways and biological processes), immune cell infiltrations, and immunoregulator expressions. The most exciting finding was that SPA17 could significantly predict anti-PDL1 and anti-PD1 therapy responses in cancer patients. Finally, specific inhibitors, like irinotecan and puromycin, which correlate with SPA17 expression in different cancer types, were also screened using Connectivity Map (CMap).ConclusionsOur results reveal that SPA17 was abnormally expressed in cancer tissues, and this expression pattern could be associated with immune cell infiltrations in tumor microenvironments. Clinically, SPA17 not only acted as a potent prognostic factor to predict the clinical outcomes of cancer patients but was also a promising immunotherapy predictive biomarker for cancer patients treated with immune-checkpoint inhibitors (ICIs).

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Section: Discussionsupporting

confidence: 93%

Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

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Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Peng

Long

et al. 2022

Front. Immunol.

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“…Even with so many immune cells infiltrating the tumour, immune escape is made possible by mechanisms like an enhanced PD-L1 expression, WNT/β-catenin pathway (T cell infiltration inhibition), FasL expression (pro-apoptotic signal for tumour infiltrating lymphocytes or TILs) and androgen receptor erasure in Sertoli cells [ 110 ]. This interest in the EMT of TGCT has led to an increased search for prognostic and diagnostic biomarkers, as described by Song et al in their recent bioinformatic analysis [ 113 ].…”

Section: Cancer and Inflammationmentioning

confidence: 99%

Testicular Germ Cell Tumours and Proprotein Convertases

Velado-Eguskiza

Gomez-Santos

Badiola

et al. 2022

Cancers

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Testicular Germ Cell Tumours (TGCT) are widely considered a “curable cancer” due to their exceptionally high survival rate, even if it is reduced by many years after the diagnosis due to metastases and relapses. The most common therapeutic approach to TGCTs has not changed in the last 50 years despite its multiple long-term side effects, and because it is the most common malignancy in young Caucasian men, much research is needed to better the quality of life of the many survivors. Proprotein Convertases (PC) are nine serine proteases responsible for the maturation of inactive proproteins with many diverse functions. Alterations in their expression have been associated with various diseases, including cancer and inflammation. Many of their substrates are adhesion molecules, metalloproteases and proinflammatory molecules, all of which are involved in tumour development. Inhibition of certain convertases has also been shown to slow tumour formation, demonstrating their involvement in this process. Considering the very established link between PCs and inflammation-related malignancies and the recent studies carried out into the immune microenvironment of TGCTs, the study of the involvement of PCs in testicular cancer may open up avenues for being both a biomarker for diagnosis and a therapeutic target.

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“…While tumor-infiltrating T-lymphocytes have been attributed to the development of malignant extracranial GCT [15], PD-L1 + tumor-associated macrophages (TAM) have been detected rather in seminomas than nonseminomas [16]. Additionally, analysis of 22 types of tumor-infiltrating immune cells revealed high infiltration of CD8+ T-cells, macrophages, and dendritic cells in GCTs compared with normal samples [17]. In other tumor entities, such as pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, or prostate cancer, highly differentiated and activated fibroblasts (cancerassociated fibroblasts; CAF) were demonstrated to enhance tumor proliferation and metastatic capacity [18][19][20][21], while inhibiting vascular-like network formation [19].…”

Section: Introductionmentioning

confidence: 99%

Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level

et al. 2022

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The tumor microenvironment (TM), consisting of the extracellular matrix (ECM), fibroblasts, endothelial cells, and immune cells, might affect tumor invasiveness and the outcome of standard chemotherapy. This study investigated the cross talk between germ cell tumors (GCT) and surrounding TM cells (macrophages, T‐lymphocytes, endothelial cells, and fibroblasts) at the transcriptome and secretome level. Using high‐throughput approaches of three‐dimensional (3D) co‐cultured cellular aggregates, this study offers newly identified pathways to be studied with regard to sensitivity toward cisplatin‐based chemotherapy or tumor invasiveness as a consequence of the cross talk between tumor cells and TM components. Mass‐spectrometry‐based secretome analyses revealed that TM cells secreted factors involved in ECM organization, cell adhesion, angiogenesis, and regulation of insulin‐like growth factor (IGF) transport. To evaluate direct cell–cell contacts, green fluorescent protein (GFP)‐expressing GCT cells and mCherry‐expressing TM cells were co‐cultured in 3D. Afterward, cell populations were separated by flow cytometry and analyzed by RNA sequencing. Correlating the secretome with transcriptome data indicated molecular processes such as cell adhesion and components of the ECM being enriched in most cell populations. Re‐analyses of secretome data with regard to lysine‐ and proline‐hydroxylated peptides revealed a gain in proteins, such as collagens and fibronectin. Cultivation of GCT cells on collagen I/IV‐ or fibronectin‐coated plates significantly elevated adhesive and migratory capacity, while decreasing cisplatin sensitivity of GCT cells. Correspondingly, cisplatin sensitivity was significantly reduced in GCT cells under the influence of conditioned medium from fibroblasts and endothelial cells. This study sheds light on the cross talk between GCT cells and their circumjacent TM, which results in deposition of the ECM and eventually promotes a pro‐tumorigenic environment through enhanced migratory and adhesive capacity, as well as decreased cisplatin sensitivity. Hence, our observations indicate that targeting the ECM and its cellular components might be a novel therapeutic option in combination with cisplatin‐based chemotherapy for GCT patients.

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Identification of new biomarkers in immune microenvironment of testicular germ cell tumour

Cited by 8 publications

References 51 publications

Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Sperm Autoantigenic Protein 17 Predicts the Prognosis and the Immunotherapy Response of Cancers: A Pan-Cancer Analysis

Testicular Germ Cell Tumours and Proprotein Convertases

Profiling the 3D interaction between germ cell tumors and microenvironmental cells at the transcriptome and secretome level

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