Next-generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer

Xie, Ni; Yao, Yujiang; Wan, Lili; Zhu, Ting; Liu, Litao; Yuan, Jun

doi:10.3892/etm.2017.4464

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…S1A) following diagnosis and was also positively associated with the stage of the disease (Fig. S1B), the latter being consistent with the reported presence of ETV1 in lymph node metastases (80). These data strongly support the notion that ETV1 promotes colorectal tumor formation and may be a predictor of an unfavorable outcome.…”

Section: Resultssupporting

confidence: 88%

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

Song

Freeman

et al. 2020

Int J Oncol

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ETS variant 1 (ETV1) is an oncogenic transcription factor. However, its role in colorectal cancer has remained understudied. The present study demonstrated that ETV1 downregulation led to reduced HCT116 colorectal cancer cell growth and clonogenic activity. Furthermore, the ETV1 mRNA levels were enhanced in colorectal tumors and were associated with disease severity. In addition, ETV1 directly bound to Jumonji C domain-containing (JMJD) 1A, a histone demethylase known to promote colon cancer. ETV1 and JMJD1A, but not a catalytically inactive mutant thereof, cooperated in inducing the matrix metalloproteinase (MMP)1 gene promoter that was similar to the cooperation between ETV1 and another histone demethylase, JMJD2A. RNA-sequencing revealed multiple potential ETV1 target genes in HCT116 cells, including the FOXQ1 and TBX6 transcription factor genes. Moreover, JMJD1A co-regulated FOXQ1 and other ETV1 target genes, but not TBX6, whereas JMJD2A downregulation had no impact on FOXQ1 as well as TBX6 transcription. Accordingly, the FOXQ1 gene promoter was stimulated by ETV1 and JMJD1A in a cooperative manner, and both ETV1 and JMJD1A bound to the FOXQ1 promoter. Notably, the overexpression of FOXQ1 partially reversed the growth inhibitory effects of ETV1 ablation on HCT116 cells, whereas TBX6 impaired HCT116 cell growth and may thereby dampen the oncogenic activity of ETV1. The latter also revealed for the first time, to the best of our knowledge, a potential tumor suppressive function of TBX6. Taken together, the present study uncovered a ETV1/JMJD1A-FOXQ1 axis that may drive colorectal tumorigenesis.

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Section: Resultssupporting

confidence: 88%

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

Song

Freeman

et al. 2020

Int J Oncol

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“…Test results can be helpful for the initial diagnosis, tumor classification, determining the origin of the cancer, and prognosis. 76 Table 2 77 – 130 provides a partial list of cancers where NGS information has provided value for managing patients. Thyroid nodules are a specific example where fine needle aspiration and cytologic examination may not yield a definitive diagnosis, while NGS has been shown to have high specificity and sensitivity for cancer detection.…”

Section: Next-generation Sequencing Applications In Oncologymentioning

confidence: 99%

A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?

et al. 2018

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Next-generation sequencing refers to a high-throughput technology that determines the nucleic acid sequences and identifies variants in a sample. The technology has been introduced into clinical laboratory testing and produces test results for precision medicine. Since next-generation sequencing is relatively new, graduate students, medical students, pathology residents, and other physicians may benefit from a primer to provide a foundation about basic next-generation sequencing methods and applications, as well as specific examples where it has had diagnostic and prognostic utility. Next-generation sequencing technology grew out of advances in multiple fields to produce a sophisticated laboratory test with tremendous potential. Next-generation sequencing may be used in the clinical setting to look for specific genetic alterations in patients with cancer, diagnose inherited conditions such as cystic fibrosis, and detect and profile microbial organisms. This primer will review DNA sequencing technology, the commercialization of next-generation sequencing, and clinical uses of next-generation sequencing. Specific applications where next-generation sequencing has demonstrated utility in oncology are provided.

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“…47% of 100 colorectal cancer tissues had high expression of ER81 (ETV1), however, its expression level was not correlated with the clinicopathological findings and expression of MMPs [25]. Genetic screening findings from 39 patients with colorectal cancer showed ETV1 was significantly correlated with the lymphatic metastasis of colorectal cancer [26]. However, another study reported that ETV1 expression was not related to the clinicopathological findings [25].…”

Section: Introductionmentioning

confidence: 99%

Glucose-Regulated Protein 94 Mediates the Proliferation and Metastasis through the Regulation of ETV1 and MAPK Pathway in Colorectal Cancer

Batzorig¹,

Wei²,

Wang³

et al. 2021

Int. J. Med. Sci.

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Colorectal cancer (CRC) is a worldwide health problem. Glucose-regulated protein 94 (GRP94) is known as an important endoplasmic reticulum-stress response protein that shows correlation with aggressive cancer behavior. However, the role of GRP94 in CRC is still unclear. Our results showed that silencing GRP94 (GRP94-KD) reduced cell proliferation, invasion and migration of CRC cells and suppressed tumorigenesis in the xenograft mouse model. Rescue assay showed that ETV1 overexpression reversed the effect of GRP94 on cell proliferation and migration. In the molecular mechanism, we found that knockdown of GRP94 inhibited the level of MAPK pathway, including ERK/p-ERK, JNK/p-JNK, and p38/p-p38 signals. Cyclooxygenase-2 and epithelial-mesenchymal transformation biomarkers, such as N-cadherin, vimentin, and β-catenin were suppressed in GRP94 knockdown cells. Treatment of specific inhibitors of MAPK pathway showed that ERK/p-ERK, and p38/p-p38 inhibitors significantly influenced ETV1 expression as compared to JNK/p-JNK inhibitor. Our results indicated that silencing GRP94 repressed the ability of EMT process, cancer cell proliferation, metastasis, and CRC tumorigenesis. Therefore, GRP94 may play an important role in CRC by regulating ETV1 and MAPK pathway.

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Next-generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer

Cited by 15 publications

References 23 publications

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

Cooperation between ETS transcription factor ETV1 and histone demethylase JMJD1A in colorectal cancer

A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?

Glucose-Regulated Protein 94 Mediates the Proliferation and Metastasis through the Regulation of ETV1 and MAPK Pathway in Colorectal Cancer

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