Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis

Pan, Hui; Liu, Lu; Cui, Junqi; Yang, Yuan; Wang, Zhaoyang; Fan, Xianqun

doi:10.18632/aging.102693

Cited by 19 publications

(17 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This conclusion was similar to the previous one that higher tumor mutation burden tends to achieve a prognosis and to promote the infiltrations of immune cells such as T cells and NK cells in bladder cancer [43]. Pan et al proved that the infiltration of immune cells is closely related to tumor progression and prognosis [44]. The reason that there is no difference in immune score between C1 and C2 in our study may be the small sample size.…”

Section: Discussionsupporting

confidence: 91%

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Liu

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP − GC). Methods: The clinical, gene expression profile data and AS events of 138 HP − GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP − GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan-Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP − GC. Finally, splicing networks were constructed using Cytoscape. Results: A total of 48141 AS events and 1041 DEAS events were found in HP − GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. Conclusion: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP − GC and can be used as prognostic factors to establish an effective nomogram.

show abstract

Section: Discussionsupporting

confidence: 91%

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Liu

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…We show that the IDO1 expression is strongly associated with poor overall survival, prompting further investigations of IDO's possible prognostic role. IDO1 and CD8+ T cell signature prognostic roles were also identified by other groups in the analysis of the same datasets [ 70 , 71 ]. Moreover, IDO1 was among the most highly expressed genes in UM with chromosome 3 monosomy, a group characterized by an increased metastatic risk [ 33 ].…”

Section: Discussionmentioning

confidence: 70%

Bioinformatic Analysis Reveals Central Role for Tumor-Infiltrating Immune Cells in Uveal Melanoma Progression

Lachota

Lennikov

Malmberg

et al. 2021

Journal of Immunology Research

View full text Add to dashboard Cite

Tumor-infiltrating immune cells are capable of effective cancer surveillance, and their abundance is linked to better prognosis in numerous tumor types. However, in uveal melanoma (UM), extensive immune infiltrate is associated with poor survival. This study aims to decipher the role of different tumor-infiltrating cell subsets in UM in order to identify potential targets for future immunotherapeutic treatment. We have chosen the TCGA-UVM cohort as a training dataset and GSE22138 as a testing dataset by mining publicly available databases. The abundance of 22 immune cell types was estimated using CIBERSORTx. Then, to determine the significance of tumor-infiltrating cell subsets in UM, we built a multicell type prognostic signature, which was validated in the testing cohort. The created signature was built upon the negative prognostic role of CD8+ T cells and M0 macrophages and the positive role of neutrophils. Based on the created signature score, we divided the patients into low- and high-risk groups. Kaplan-Meier, Cox, and ROC analyses demonstrated superior performance of our risk score compared to either clinical or pathologic characteristics of both cohorts. Further, we found the molecular pathways associated with cancer immunoevasion and metastasis to be enriched in the high-risk group, explaining both the lack of adequate immune surveillance despite increased infiltration of CD8+ T cells as well as the higher metastatic potential. Genes associated with tryptophan metabolism (IDO1 and KYNU) and metalloproteinases were among the most differentially expressed between the high- and low-risk groups. Our correlation analyses interpreted in context of published in vitro data strongly suggest the central role of CD8+ T cells in shifting the UM tumor microenvironment towards suppressive and metastasis-promoting. Therefore, we propose further investigations of IDO1 and metalloproteinases as novel targets for immunotherapy in lymphocyte-rich metastatic UM patients.

show abstract

“…We estimated immune score and stromal score based on gene expression data using the ESTIMATE algorithm ( Xie et al, 2019 ; Mahal et al, 2020 ; Pan et al, 2020 ). Both scores were correlated with lymphatic invasion ( P = 0.0005 and P = 0.0008, respectively).…”

Section: Resultsmentioning

confidence: 99%

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

Guo

Wang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Ovarian cancer (OC) is the deadliest gynecological cancer in women. Immune cell infiltration has a critical role in regulating carcinogenesis and prognosis in OC. To identify prognostic genes relevant to the tumor microenvironment in OC, we investigated the association between OC and gene expression profiles. Results obtained with the ESTIMATE R tool showed that immune score and stromal score were correlated with lymphatic invasion, and high immune score predicted a favorable prognosis. A total of 342 common differentially expressed genes were identified according to the two scores; these genes were mainly involved in immune response, extracellular region, and serine-type endopeptidase activity. Three immune-related prognostic genes were selected by univariate and multivariate Cox regression analysis. We further established a prognostic model and validated the prognostic value of three hub genes in different databases; our results showed that this model could accurately predict survival and evaluate prognosis independent of clinical characteristics. Three hub genes have prognostic value in OC. TIMER analysis revealed that the three genes were correlated with different immune cells. Low levels of macrophage infiltration and high levels of CD4+ T cell infiltration were associated with favorable survival outcomes. Arm-level gain of GYPC was correlated with neutrophils and dendritic cells. These findings indicate that CXCR4, GYPC, and MMP12 modulate prognosis via effects on the infiltration of immune cells. Thus, these genes represent potential targets for immune therapy in OC.

show abstract

Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis

Cited by 19 publications

References 50 publications

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

Bioinformatic Analysis Reveals Central Role for Tumor-Infiltrating Immune Cells in Uveal Melanoma Progression

Three Genes Predict Prognosis in Microenvironment of Ovarian Cancer

Contact Info

Product

Resources

About