Tumor Mutation Burden Predicts Relapse in Papillary Thyroid Carcinoma With Changes in Genes and Immune Microenvironment

Guo, Mingming; Chen, Zhe; Li, Yayi; Li, Sijin; Shen, Fei; Gan, Xiao‐Xiong; Feng, Jianhua; Cai, Wei; Liu, Qingzhi; Xu, Bo

doi:10.3389/fendo.2021.674616

“…Through the univariate Cox regression analysis, we found that 5 mRNAs (IL37, SOD3, HAND2, IPCEF1, and GAS2L2) and 4 miRNAs (has-mir-514a-5p, has-mir-514a-3p, has-mir-486-5p, and has-mir-486-3p) were correlated with the prognostic rate in PTC patients with RAI therapy. Previous studies have observed that IL37 and SOD3 expressions were connected with poor prognosis in PTC ( 24 , 44 ). Regrettably, IL37 and SOD3 genes did not enter our final prognostic model.…”

Section: Discussionmentioning

confidence: 86%

“…Moreover, dysregulated RNAs have been implicated in contributing to the occurrence, metastasis, and prognosis of PTC ( 9 , 22 – 24 ). For example, a higher expression of interleukin 37 (IL37) and a lower expression of HIG1 hypoxia-inducible domain family member 1B (HIGD1B), polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9), and serum deprivation-response protein (SDPR) in PTC tissues predict worse outcomes ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, dysregulated RNAs have been implicated in contributing to the occurrence, metastasis, and prognosis of PTC ( 9 , 22 – 24 ). For example, a higher expression of interleukin 37 (IL37) and a lower expression of HIG1 hypoxia-inducible domain family member 1B (HIGD1B), polypeptide N-acetylgalactosaminyltransferase 9 (GALNT9), and serum deprivation-response protein (SDPR) in PTC tissues predict worse outcomes ( 24 , 25 ). In addition, higher expressions of differentially regulated miRNAs, including miR-221, miR-146, miR-193, miR-182, miR-486, and miR-564, are correlated with increased risk of metastasis and poor prognosis in PTC ( 9 , 22 , 23 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer

Liu

¹

,

Shi

²

,

Lai

³

et al. 2022

Front. Endocrinol.

1

0

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Papillary thyroid cancer (PTC) accounts for about 90% of thyroid cancer. There are approximately 20%–30% of PTC patients showing disease persistence/recurrence and resistance to radioactive iodine (RAI) treatment. For these PTC patients with RAI refractoriness, the prognosis is poor. In this study, we aimed to establish a comprehensive prognostic model covering multiple signatures to increase the predictive accuracy for progression-free survival (PFS) of PTC patients with RAI treatment. The expression profiles of mRNAs and miRNAs as well as the clinical information of PTC patients were extracted from TCGA and GEO databases. A series of bioinformatics methods were successfully applied to filtrate a two-RNA model (IPCEF1 and hsa-mir-486-5p) associated with the prognosis of RAI-therapy. Finally, the RNA-based risk score was calculated based on the Cox coefficient of the individual RNA, which achieved good performances by the time-dependent receiver operating characteristic (tROC) curve and PFS analyses. Furthermore, the predictive power of the nomogram, integrated with the risk score and clinical parameters (age at diagnosis and tumor stage), was assessed by tROC curves. Collectively, our study demonstrated high precision in predicting the RAI response of PTC patients.

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“…Increasing evidence demonstrates that macrophage transitions from M1 to M2 phenotypes might boost cancer initiation and progression by promoting cell proliferation, metastasis, drug reliance, and immune evasion 24 , 25 . Previous studies also showed that CD68 and CD206 are markers of macrophages and M2 macrophages and increased density of TAMs is associated with poor survival of patients 26 . Consistent with previous studies, we found that the infiltration of macrophages was high in KIRC tissues, and the degree of infiltration was correlated to the poor prognosis of tumors by analyzing the TCGA database.…”

Section: Discussionmentioning

confidence: 88%

Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Zhang

¹

,

Zheng

²

,

Yu

³

et al. 2022

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Tumor-derived exosomes play a pivotal role in regulating tumor progression by mediating crosstalk between tumor cells and immune cells such as macrophages within the tumor microenvironment. Macrophages can adopt two distinct polarization statuses and switch between M1 or M2 activation phenotypes in response to the different external stimuli. However, the role of tumor derived exosomes in the macrophage phenotypic switch and tumor development have not been elucidated in renal cell carcinoma (RCC). Here we found that high macrophage infiltration was associated with worse prognosis in RCC patients, therefore we propose our hypothesis that RCC derived exosomes might directly influence macrophage polarization and thus promote tumor progression. Both cell-based in vitro models and orthotopic transplantation in vivo tumor models were constructed and ELISA, flow cytometry, and macrophage functional studies were performed to investigate whether and how RCC-derived exosomes regulate macrophage polarization and tumor growth. The results found that these exosomes promote macrophage polarization, cytokine release, phagocytosis, angiogenesis, and tumor development. Further study revealed high amount of a recently discovered lncRNA called lncARSR in RCC-derived exosomes. Overexpression of lncARSR induced phenotypic and functional changes of macrophages in vitro and promoted tumor growth in vivo , while knockdown of lncARSR by siRNA disrupted the exosomes-mediated macrophage polarization. LncARSR interacts directly with miR-34/miR- 449 to increase STAT3 expression and mediate macrophage polarization in RCC cells. Together, RCC-derived exosomes facilitate the development of tumor through inducing macrophage polarization via transferring lncARSR, suggesting that RCC-derived exosomes, lncARSR and STAT3 are the potential therapeutic targets for treatment of RCC.

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“…The majority of studies demonstrated that TMB was related to prognosis and could be a marker for predicting the effectiveness of immune checkpoint inhibitors in cancer [ 42 , 43 ]. Mutation genes related to TMB were crucial prognostic biomarkers for cancers [ 32 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

Guo

¹

,

Shen

²

,

Sun

³

et al. 2023

Journal of Oncology

1

0

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Background. Esophageal cancer (EC) had the sixth-highest mortality rate of all cancers due to its poor prognosis. Immune cells and mutation genes influenced the prognosis of EC, but their combined effect on predicting EC prognosis was unknown. In this study, we comprehensively analyzed the immune cell infiltration (ICI) and mutation genes and their combined effects for predicting prognosis in EC. Methods. The CIBERSORT and ESTIMATE algorithms were used to analyse the ICI scape based on the TCGA and GEO databases. EC tissues and pathologic sections from Huai’an, China, were used to verify the key immune cells and mutation genes and their interactions. Results. Stromal/immune score patterns and ICI/gene had no statistical significance in overall survival (OS) ( p > 0.05 ). The combination of ICI and tumor mutation burden (TMB) showed that the high TMB and high ICI score group had the shortest OS ( p = 0.004 ). We recognized that the key mutation gene NRF2 was significantly different in the high/low ICI score subgroups ( p = 0.002 ) and positivity with mast cells (MCs) ( p < 0.05 ). Through experimental validation, we found that the MCs and activated mast cells (AC-MCs) were more infiltration in stage II/III ( p = 0.032 ; p = 0.013 ) of EC patients and that NRF2 expression was upregulated in EC ( p = 0.045 ). AC-MCs combined with NRF2 had a poor prognosis, according to survival analysis ( p = 0.056 ) and interactive analysis ( p = 0.032 ). Conclusions. We presume that NRF2 combined with AC-MCs could be a marker to predict prognosis and could influence immunotherapy through regulating PD-L1 in the EC.

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Tumor Mutation Burden Predicts Relapse in Papillary Thyroid Carcinoma With Changes in Genes and Immune Microenvironment

Cited by 11 publications

References 54 publications

Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer

Construction of a Signature Model to Predict the Radioactive Iodine Response of Papillary Thyroid Cancer

Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

Activated Mast Cells Combined with NRF2 Predict Prognosis for Esophageal Cancer

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