COL1A1: A potential therapeutic target for colorectal cancer expressing wild-type or mutant KRAS

Zhang, Zheying; Fang, Cheng; Wang, Yongxia; Zhang, Jinghang; Yu, Jian; Zhang, Yongxi; Wang, Xianwei; Zhong, Jiateng

doi:10.3892/ijo.2018.4536

Cited by 32 publications

(31 citation statements)

References 43 publications

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“…Brooks et al (36) found that the high COL1A1 expression level was associated with poor survival in patients with NMIBC, which was in line with our results. In addiation, increasing evidence confirmed that inhibition of COL1A1 could significantly suppress cancer cells proliferation, clonogenicity, and invasion, indicating that COL1A1 is a putative therapeutic target for cancer (35,37,38). COMP, encoding a non-collagenous extracellular matrix protein, is up-regulated in various cancers and involved in cancer cell proliferation, tumorigenesis, epithelial-mesenchymal transition, and stemness features (39)(40)(41).…”

Section: Discussionmentioning

confidence: 96%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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The tumor microenvironment (TME) is a complex system that plays an important role in tumor development and progression, but the current knowledge about its effect on bladder cancer (BC) is scarce. In this study, we performed a comprehensive analysis of the relationship between the TME and gene expression profiles to identify prognostic biomarkers for BC. The ESTIMATE algorithm was used to calculate immune and stromal scores of BC patients who were obtained from the Gene Expression Omnibus database. We found that the immune and stromal scores were associated with clinical characteristics and the prognosis of BC patients. Based on these scores, 104 immune-related differentially expressed genes were identified. Further, functional enrichment analysis revealed that these genes were mainly involved in the immune-related biological processes and signaling pathways. Three prognostic genes were then identified and used to establish a risk prediction model using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of COL1A1, COMP, and SERPINE2 significantly correlated with cancer-specific survival and overall survival of BC patients. Additionally, we validated the prognostic values of these genes using two independent cohorts from The Cancer Genome Atlas and Gene Expression Omnibus databases. Finally, the relationships between the three prognostic genes and several immune cells were evaluated using Tumor Immune Estimation Resource, indicating that the expression levels of COL1A1, COMP, and SERPINE2 correlated positively with the tumor infiltration levels of CD4 + T cells and macrophages. In conclusion, the current study comprehensively analyzed the TME and presented immune-related prognostic genes for BC, providing new insights into immunotherapeutic strategies for BC patients.

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Section: Discussionmentioning

confidence: 96%

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Teng

Liu

et al. 2020

Front. Oncol.

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“…Out of nine genes differentially expressed in our study, five are included in the PI3K-AKT pathway, with three of them-FN1, NGFR, and THBS1-being associated with tumor progression [65][66][67][68]. Besides, upregulated ANGPT1 and downregulated COl11A1 are related to a better prognosis in lung cancer metastasis and proliferation in colorectal cancer [68,69]. Another gene, TNFSF10, was identified as upregulated in U251MTAP−/−.…”

Section: Discussionmentioning

confidence: 99%

Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Menezes

Silva

Gomes

et al. 2020

Cells

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The 5’-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients’ clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients’ clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP’s role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

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“…Using genome arrays, we ultimately identified COL1A1 as a relevant marker due to high expression in tumor samples and interconnectedness with other hub genes. This gene encodes the pro-alpha1 chains of type I collagen ( Zhang et al, 2018b ; Zhang et al, 2018a , p. 1). COL1A1 is often found in connective tissues (e.g., bone and tendon) and thus its mutation is most closely associated with osteogenic diseases, specifically osteogenesis imperfecta ( Palomo, Vilaça & Lazaretti-Castro, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies investigating the mechanistic link between fibrosis and lymph node metastasis will help in further validating COL1A1’s role in cancer progression. The identification of COL1A1 as a key part of this process may lead to druggable targets (i.e., Halofuginone ( Zhang et al, 2018a )) which can delay progression of LSCC to the lymph nodes. In addition, it is a valuable prognostic marker which may aid clinicians in accurately staging the disease.…”

Section: Discussionmentioning

confidence: 99%

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

Dong

Zhu

Zhang

2020

PeerJ

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Background Squamous cell carcinomas of the lung are an extremely common and deadly form of non-small cell lung cancers. Clinical management of the disease is dependent on staging and metastatic status. Metastasis to the lymph node is especially crucial to diagnose as it occurs at an earlier stage. However, lymphadenectomies are invasive and tumor cells may be overlooked during evaluation.There are limited approved biomarkers for predicting lymph node metastasis with squamous cell carcinomas of the lung (LSCC). Methods Genome data of 60 tumor-adjacent samples were downloaded from Genome Expression Omnibus. We identified over-expressed HUB genes using Cytoscape as key prognostic markers. The selected markers were further evaluated based on gene ontology and overall expression levels compared to normal tissue using The Cancer Genome Atlas. We further validated these results using clinical biopsy tissue taken from squamous cell carcinoma patients. Results Analysis of the genome expression data resulted in 13 relevant hub genes that were differentially expressed in cancerous samples. All of these genes are associated with collagen biosynthesis within the tumor microenvironment. We chose Collagen Type 1 Alpha 1 (COL1A1) as the most relevant prognostic marker due to its high number of pathway connections and over expression in the tumor microenvironment compared to the other 12 genes. Additionally, based on analysis of The Cancer Genome Atlas, tumors with higher levels of COL1A1 expression are associated with poorer overall survival. Finally, evaluation of clinical biopsy samples suggests that overexpression of COL1A1 in the LSCC microenvironment highly correlates with lymph node metastasis. These results suggest COL1A1 is a clinically relevant marker that should be used to justify lymphadenectomies.

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COL1A1: A potential therapeutic target for colorectal cancer expressing wild-type or mutant KRAS

Cited by 32 publications

References 43 publications

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Prognostic Value of Immune-Related Genes in the Tumor Microenvironment of Bladder Cancer

Loss of 5′-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness

Expression of collagen type 1 alpha 1 indicates lymph node metastasis and poor outcomes in squamous cell carcinomas of the lung

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