Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression

Zhao, Zhiwei; Lian, Wen-Jing; Zhou, Hongying; Wang, Guiming; Cao, Xiaofeng; Yang, Huijun; Hou, Yiping

doi:10.3892/or.2012.1693

Cited by 8 publications

(4 citation statements)

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“…ZEB2 is known to regulate epithelial to mesenchymal transition (EMT) and drive proliferation and differentiation 34 . Downregulation of RGMA is reported in colorectal and breast cancer and has been associated with cancer progression and poor prognosis 35,36 . We also identified SNVs that were in close proximity to post-translational modification sites.…”

Section: Discussionmentioning

confidence: 99%

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

Jain

Patel

Pinto

et al. 2019

Sci Rep

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Epidermal growth factor receptor (EGFR) targeted therapies have shown limited efficacy in head and neck squamous cell carcinoma (HNSCC) patients despite its overexpression. Identifying molecular mechanisms associated with acquired resistance to EGFR-TKIs such as erlotinib remains an unmet need and a therapeutic challenge. In this study, we employed an integrated multi-omics approach to delineate mechanisms associated with acquired resistance to erlotinib by carrying out whole exome sequencing, quantitative proteomic and phosphoproteomic profiling. We observed amplification of several genes including AXL kinase and transcription factor YAP1 resulting in protein overexpression. We also observed expression of constitutively active mutant MAP2K1 (p.K57E) in erlotinib resistant SCC-R cells. An integrated analysis of genomic, proteomic and phosphoproteomic data revealed alterations in MAPK pathway and its downstream targets in SCC-R cells. We demonstrate that erlotinib-resistant cells are sensitive to MAPK pathway inhibition. This study revealed multiple genetic, proteomic and phosphoproteomic alterations associated with erlotinib resistant SCC-R cells. Our data indicates that therapeutic targeting of MAPK pathway is an effective strategy for treating erlotinib-resistant HNSCC tumors.

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Section: Discussionmentioning

confidence: 99%

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

Jain

Patel

Pinto

et al. 2019

Sci Rep

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“…Studies have found that FSTL3 can promote the metastasis of tumor cells by forming an inhibitory immune microenvironment [30,31] , and promote the polarization of macrophages and broblasts [32] . RGMA acts as a tumor suppressor gene in colorectal cancer, breast cancer, prostate cancer, lymphoma and other tumors [33][34][35] . In a study of colorectal cancer, it was found that overexpression of RGMA inhibited the proliferation, migration and invasion of tumor cells, and increased cell apoptosis, which can be used as an important marker for early diagnosis and prognosis of tumors [36] .…”

Section: Discussionmentioning

confidence: 99%

Prediction of Risk and Clinical Outcome of cuproptosis in Lung Squamous carcinoma

Zhang

Zhou

et al. 2023

Preprint

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Background: Lung squamous cell carcinoma (LUSC) is a common histopathologic type of lung cancer, and chemotherapy is still the main means for advanced LUSC. Cuproptosis is a newly discovered form of cell death different from known programmed apoptosis, which regulates the proliferation and progression of tumor cells. However, the molecular mechanism and prognosis of cuproptosis-related genes (CRGs) in LUSC have not yet been reported. Methods: RNA sequencing profiles and related clinical data of LUSC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and combined into a new LUSC cohort. The data were processed using multiple R packets, and CRGs associated with the prognosis of pulmonary squamous carcinoma were screened based on differences in gene expression. Through the interaction network analysis of tumor mutation load, copy number variation and CRGs, the patients were divided into two subtypes according to the expression of CRGs, and three different gene clusters according to the difference in gene expression. The key differential genes were screened to construct prognostic markers, and the correlation between LUSC immune cell infiltration and immunity was further analyzed. A more accurate nomogram map was constructed by risk score and clinical factors. In addition, drug sensitivity analysis was performed on CRGs of LUSC. Results: Patients were divided into two cuproptosis-related subtypes and subsequently regrouped into three gene clusters, showing different immune infiltrations. The results of risk score showed that compared with the low-score risk group, the high-score risk group had higher tumor microenvironment score, lower frequency of tumor mutational burden, poor prognosis. At the same time, high-score risk group had higher sensitivity to chemotherapy of cisplatin, doxorubicin, etoposide, paclitaxel, vinorelbine and other drugs. Conclusions: We developed a new scoring system to predict the prognosis and immune status of patients with LUSC. This feature shows a satisfactory predictive effect and has the potential to guide patients' integrative treatment.

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“…Studies have found that FSTL3 can promote the metastasis of tumor cells by forming an inhibitory immune microenvironment [ 38 , 39 ], and promote the polarization of macrophages and fibroblasts [ 40 ]. RGMA acts as a tumor suppressor gene in colorectal cancer, breast cancer, prostate cancer, lymphoma and other tumors [ 41 – 43 ]. In a study of colorectal cancer, it was found that overexpression of RGMA inhibited the proliferation, migration and invasion of tumor cells, and increased cell apoptosis, which can be used as an important marker for early diagnosis and prognosis of tumors [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction of risk and clinical outcome of cuproptosis in lung squamous carcinoma

Zhang¹,

Zhou²,

Li³

et al. 2023

BMC Pulm Med

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Background Lung squamous cell carcinoma (LUSC) is an important subtype of non-small cell lung cancer. Its special clinicopathological features and molecular background determine the limitations of its treatment. A recent study published on Science defined a newly regulatory cell death (RCD) form – cuproptosis. Which manifested as an excessive intracellular copper accumulation, mitochondrial respiration-dependent, protein acylation-mediated cell death. Different from apoptosis, pyroptosis, necroptosis, ferroptosis and other forms of regulatory cell death (RCD). The imbalance of copper homeostasis in vivo will trigger cytotoxicity and further affect the occurrence and progression of tumors. Our study is the first to predict the prognosis and immune landscape of cuproptosis-related genes (CRGs) in LUSC. Methods The RNA-seq profiles and clinical data of LUSC patients were downloaded from TCGA and GEO databases and then combined into a novel cohort. R language packages are used to analyze and process the data, and CRGs related to the prognosis of LUSC were screened according to the differentially expressed genes (DEGs). After analyzed the tumor mutation burden (TMB), copy number variation (CNV) and CRGs interaction network. Based on CRGs and DEGs, cluster analysis was used to classify LUSC patients twice. The selected key genes were used to construct a CRGs prognostic model to further analyze the correlation between LUSC immune cell infiltration and immunity. Through the risk score and clinical factors, a more accurate nomogram was further constructed. Finally, the drug sensitivity of CRGs in LUSC was analyzed. Results Patients with LUSC were divided into different cuproptosis subtypes and gene clusters, showing different levels of immune infiltration. The risk score showed that the high-risk group had higher tumor microenvironment score, lower tumor mutation load frequency and worse prognosis than the low-risk group. In addition, the high-risk group was more sensitive to vinorelbine, cisplatin, paclitaxel, doxorubicin, etoposide and other drugs. Conclusions Through bioinformatics analysis, we successfully constructed a prognostic risk assessment model based on CRGs, which can not only accurately predict the prognosis of LUSC patients, but also evaluate the patient 's immune infiltration status and sensitivity to chemotherapy drugs. This model shows satisfactory predictive results and provides a reference for subsequent tumor immunotherapy.

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Decreased expression of repulsive guidance molecule member A by DNA methylation in colorectal cancer is related to tumor progression

Cited by 8 publications

References 0 publications

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma

Prediction of Risk and Clinical Outcome of cuproptosis in Lung Squamous carcinoma

Prediction of risk and clinical outcome of cuproptosis in lung squamous carcinoma

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