Comprehensive Analysis of the Potential Immune-Related Biomarker Transporter Associated With Antigen Processing 1 That Inhibits Metastasis and Invasion of Ovarian Cancer Cells

Li, Xiaoxue; Zeng, Songshan; Ding, Yiling; Nie, Yanting; Yang, Mengyuan

doi:10.3389/fmolb.2021.763958

Cited by 9 publications

(6 citation statements)

References 34 publications

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“…Anika Tabassum et al found that prognostic analysis on the OV showed a positive correlation for TAP1 expression, while it is negative on BRCA, LIHC, and LUAD [ 11 ]. In patients with ovarian cancer, TAP1 protein abundance was negatively correlated with survival time and significantly correlated with immune infiltration and poor prognosis [ 12 ].Therefore, there is no consistent relationship between TAP1 expression and patient prognosis in different cancer types.…”

Section: Discussionmentioning

confidence: 99%

“…TAP1 is involved in antigen transport from the cytoplasm to the endoplasmic reticulum, binds to major histocompatibility complex (MHC) class I molecules, forms the molecular scaffold for the final stage of MHC class I folding, and then presents MHC I to immune cells, thereby serving as a target for tumor cells [ 10 ]. Recent studies have shown that TAP1 is closely associated with various tumors and has the potential to become a novel tumor-targeting drug [ 11 , 12 ]. Although high TAP1 expression might, in theory, make tumor cells more susceptible to cytotoxic T cell killing [ 13 ], it might reduce their susceptibility to natural killer (NK) cell–mediated lysis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma

et al. 2023

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Background TAP1 is an immunomodulation-related protein that plays different roles in various malignancies. This study investigated the transcriptional expression profile of TAP1 in uveal melanoma (UVM), revealed its potential biological interaction network, and determined its prognostic value. Methods CIBERSORT and ESTIMATE bioinformatic methods were used on data sourced from The Cancer Genome Atlas database (TCGA) to determine the correlation between TAP1 expression, UVM prognosis, biological characteristics, and immune infiltration. Gene set enrichment analysis (GSEA) was used to discover the signaling pathways associated with TAP1, while STRING database and CytoHubba were used to construct protein–protein interaction (PPI) and competing endogenous RNA (ceRNA) networks, respectively. An overall survival (OS) prognostic model was constructed to test the predictive efficacy of TAP1, and its effect on the in vitro proliferation activity and metastatic potential of UVM cell line C918 cells was verified by RNA interference. Results There was a clear association between TAP1 expression and UVM patient prognosis. Upregulated TAP1 was strongly associated with a shorter survival time, higher likelihood of metastasis, and higher mortality outcomes. According to GSEA analysis, various immunity-related signaling pathways such as primary immunodeficiency were enriched in the presence of elevated TAP1 expression. A PPI network and a ceRNA network were constructed to show the interactions among mRNAs, miRNAs, and lncRNAs. Furthermore, TAP1 expression showed a significant positive correlation with immunoscore, stromal score, CD8+ T cells, and dendritic cells, whereas the correlation with B cells and neutrophils was negative. The Cox regression model and calibration plots confirmed a strong agreement between the estimated OS and actual observed patient values. In vitro silencing of TAP1 expression in C918 cells significantly inhibited cell proliferation and metastasis. Conclusions This study is the first to demonstrate that TAP1 expression is positively correlated with clinicopathological factors and poor prognosis in UVM. In vitro experiments also verified that TAP1 is associated with C918 cell proliferation, apoptosis, and metastasis. These results suggest that TAP1 may function as an oncogene, prognostic marker, and importantly, as a novel therapeutic target in patients with UVM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma

et al. 2023

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“…In ovarian cancer, overexpression of TAP1 in OC patients leads to a poor prognosis. The high expression of TAP1 promotes tumor migration and metastasis in vivo and in vitro ( 58 ). Our study confirmed the increased mRNA levels of TAP1 in ccRCC, both in the TCGA cohort and in the FUSCC cohort, as well as the increased protein expression in the proteomic study.…”

Section: Discussionmentioning

confidence: 99%

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

et al. 2022

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Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it’s significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial–mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC.

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“…One strategy is to target and mute the immune regulators, so that functional immune signal processing is blocked, facilitating cancer cell survival. Here, 47 common ICP genes were selected and analyzed in the context of TAP1 expression, using previously described methods [29]. Spearman's correlation analysis was conducted to evaluate the correlations between TAP1 expression and levels of individual ICPs across TCGA pan-cancer types (Fig.…”

Section: Correlation Between Tap1 Expression and The Tmementioning

confidence: 99%

Pan-cancer analysis: predictive role of TAP1 in cancer prognosis and response to immunotherapy

et al. 2023

BMC Cancer

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Background Transporter associated with antigen processing 1 (TAP1) is a molecule involved in processing and presentation of major histocompatibility complex class I restricted antigens, including tumor-associated antigens. TAP1 participates in tumor immunity, and is aberrantly expressed in multiple cancer types; Methods Transcriptome profiles were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Genetic alterations, protein distribution, and interaction information for TAP1 were downloaded from cBioPortal, Human Protein Atlas and Compartmentalized Protein–Protein Interaction, respectively. Single-cell analyses of TAP1 across cancers were conducted via the Tumor Immune Single-cell Hub website. Gene set enrichment analysis was employed to investigate TAP1-associated functional mechanisms and processes. Immune cell infiltration was explored using Tumor Immune Estimation Resource 2.0. Pan-cancer correlations between TAP1 expression and immunotherapy biomarkers were explored using the Spearman’s correlation test. Associations with immunotherapy responses were also investigated using clinicopathological and prognostic information from cohorts of patients with cancer receiving immune checkpoint inhibitors. Results TAP1 expression was elevated in most cancer types and exhibited distinct prognostic value. Immune cells expressed more TAP1 than malignant cells within most tumors. TAP1 expression was significantly correlated with immune-related pathways, T-lymphocyte infiltration, and immunotherapeutic biomarkers. Clinical cohort validation revealed a significant correlation with immune therapeutic effects and verified the prognostic role of TAP1 in immunotherapy. Western blot assay indicated that TAP1 is upregulated in glioblastoma compared with adjacent normal brain tissues. Conclusion TAP1 is a robust tumor prognostic biomarker and a novel predictor of clinical prognosis and immunotherapeutic responses in various cancer types.

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Comprehensive Analysis of the Potential Immune-Related Biomarker Transporter Associated With Antigen Processing 1 That Inhibits Metastasis and Invasion of Ovarian Cancer Cells

Cited by 9 publications

References 34 publications

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma

TAP1, a potential immune-related prognosis biomarker with functional significance in uveal melanoma

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

Pan-cancer analysis: predictive role of TAP1 in cancer prognosis and response to immunotherapy

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