Development and validation of an immune and stromal prognostic signature in uveal melanoma to guide clinical therapy

Gong, Qianwen; Wan, Qi; Li, Anqi; Yu, Yubin; Ding, Xiangyu; Leng, Lin; Qi, Xiao-Liang; Hu, Liang

doi:10.18632/aging.103779

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…We also investigated the tumor microenvironment and found no statistically significant differences in the remaining immune score and tumor purity, except for the stromal score, which was higher in the MUC16 wild-type group. Thus, a higher stromal score seems to predict a worse prognosis, and Gong et al [ 20 ] also found that a higher stromal score was always associated with poor prognosis in patients with melanoma. mRNAsi in the MUC16 mutation and wild-type groups was also compared, and mRNAsi was found to be much higher in the mutation group than in the wild-type group.…”

Section: Discussionmentioning

confidence: 99%

Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort

Huang¹,

Cao²,

Wang³

et al. 2021

WJCC

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BACKGROUND MUC16 , encoding cancer antigen 125, is a frequently mutated gene in gastric cancer. In addition, MUC16 mutations seem to result in a better prognosis in gastric cancer. However, the mechanisms that lead to a better prognosis by MUC16 mutations have not yet been clarified. AIM To delve deeper into the underlying mechanisms that explain why MUC16 mutations signal a better prognosis in gastric cancer. METHODS We used multi-omics data, including mRNA, simple nucleotide variation, copy number variation and methylation data from The Cancer Genome Atlas, to explore the relationship between MUC16 mutations and prognosis. Cox regression and random survival forest algorithms were applied to search for hub genes. Gene set enrichment analysis was used to elucidate the molecular mechanisms. Single-sample gene set enrichment analysis and “EpiDISH” were used to assess immune cells infiltration, and “ESTIMATE” for analysis of the tumor microenvironment. RESULTS Our study found that compared to the wild-type group, the mutation group had a better prognosis. Additional analysis indicated that the MUC16 mutations appear to activate the DNA repair and p53 pathways to act as an anti-tumor agent. We also identified a key gene, NPY1R (neuropeptide Y receptor Y1), which was significantly more highly expressed in the MUC16 mutations group than in the MUC16 wild-type group. The high expression of NPY1R predicted a poorer prognosis, which was also confirmed in a separate Gene Expression Omnibus cohort. Further susceptibility analysis revealed that NPY1R might be a potential drug target for gastric cancer. Furthermore, in the analysis of the tumor microenvironment, we found that immune cells in the mutation group exhibited higher anti-tumor effects. In addition, the tumor mutation burden and cancer stem cells index were also higher in the mutation group than in the wild-type group. CONCLUSION We speculated that the MUC16 mutations might activate the p53 pathway and DNA repair pathway: alternatively, the tumor microenvironment may be involved.

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Section: Discussionmentioning

confidence: 99%

Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort

Huang¹,

Cao²,

Wang³

et al. 2021

WJCC

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“…However, only a limited number of patients benefit from the currently available regimens [16]. This may be due to differences in tumor-infiltrating immune cells within the tumor microenvironment, which affect the clinical outcome in cancer patients by regulating immune escape [17,18]. In pancreatic and colorectal cancer, the expression of m6A regulators is related to tumor immune cell infiltration, providing certain cues for the therapeutic response of ICIS [19,20].…”

Section: Introductionmentioning

confidence: 99%

Immune infiltration-related N6-methyladenosine RNA methylation regulators influence the malignancy and prognosis of endometrial cancer

Yang

2021

Aging

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N6-methyladenosine (m6A) RNA methylation is associated with malignant tumor progression and is modulated by various m6A RNA methylation regulator proteins. However, its role in endometrial cancer is unclear. In this work, we analyzed sequence, copy number variation, and clinical data obtained from the TCGA database. Expression was validated using real-time quantitative polymerase chain reaction and immunohistochemistry. Changes in m6A RNA methylation regulators were closely related to the clinicopathological stage and prognosis of endometrial cancer. In particular, ZC3H13, YTHDC1, and METTL14 were identified as potential markers for endometrial cancer diagnosis and prognosis. The TIMER algorithm indicated that immune cell infiltration correlated with changes in ZC3H13, YTHDC1, and METTL14 expression. Meanwhile, ZC3H13 or YTHDC1 knockdown promoted the proliferation and invasion of endometrial cancer cells. Through gene enrichment analysis, we constructed a regulatory network in order to explore the potential molecular mechanism involving ZC3H13, YTHDC1, and METTL14. Virtual screening predicted interactions of potential therapeutic compounds with METTL14 and YTHDC1. These findings advance the understanding of RNA epigenetic modifications in endometrial cancer while identifying m6A regulators associated with immune infiltration, prognosis, and potential treatment strategies.

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“…The scores represent tumor purity. In many malignant tumors such as primary gastric cancer [ 38 ] and uveal melanoma [ 39 ], the higher the score, the higher the purity of tumor cells and the worse the prognosis. Meanwhile, a higher immune score represents the more robust immune activity of the tumor so that patients may benefit from immunotherapy [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy

Gao

Geng

et al. 2022

International Journal of Endocrinology

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DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues ( p < 0.01 ). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, p = 0.048 ). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA ( p < 0.05 ). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues ( p = 0.011 ). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues ( p = 0.011 ). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy.

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Development and validation of an immune and stromal prognostic signature in uveal melanoma to guide clinical therapy

Cited by 5 publications

References 26 publications

Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort

Why MUC16 mutations lead to a better prognosis: A study based on The Cancer Genome Atlas gastric cancer cohort

Immune infiltration-related N6-methyladenosine RNA methylation regulators influence the malignancy and prognosis of endometrial cancer

DPP4 Is a Potential Prognostic Marker of Thyroid Carcinoma and a Target for Immunotherapy

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