<i>NKX6.1</i> hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy

Chang, Shu–Jen; Kuo, Chih-Chi; Wu, Chang‐Chieh; Hsiao, Cheng–Wen; Hu, Je-Ming; Hsu, Chih-Hsiung; Chou, Yu-Ching; Shih, Yu‐Lueng; Lin, Ya-Wen

doi:10.1002/gcc.22529

Cited by 19 publications

(23 citation statements)

References 55 publications

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“…In addition to our reports, the differential methylation of NKX6.1 has also been observed in various types of cancer including B-cell lymphoma [ 24 ], acute lymphoblastic leukemia [ 25 ], astrocytoma [ 26 ] and gastric cancer [ 27 , 28 ]. Moreover, we recently demonstrated that NKX6.1 methylation was an independent indicator of 5-year disease-free survival in stage II CRC patients receiving adjuvant chemotherapy [ 29 , 30 ]. Our findings suggested that NKX6.1 hypermethylation is related to the chemotherapy response and has medical potential in optimizing the selection of therapy.…”

Section: Introductionmentioning

confidence: 99%

NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer

Chung

Lee

et al. 2020

IJMS

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Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified NKX6.1 hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through the epigenetic regulation of the epithelial-to-mesenchymal transition (EMT) in cervical cancer. More recently, we have demonstrated that NKX6.1 methylation is related to the chemotherapy response in colorectal cancer (CRC). Nevertheless, the biological function of NKX6.1 in the tumorigenesis of CRC remains unclear. In this study, we showed that NKX6.1 suppresses tumorigenic and metastatic ability both in vitro and in vivo. NKX6.1 represses cell invasion partly through the modulation of EMT. The overexpression of NKX6.1 enhances chemosensitivity in CRC cells. To further explore how NKX6.1 exerts its tumor-suppressive function, we used RNA sequencing technology for comprehensive analysis. The results showed that differentially expressed genes (DEGs) were mainly related to cell migration, response to drug, transcription factor activity, and growth factor activity, suggesting that these DEGs are involved in the function of NKX6.1 suppressing cancer invasion and metastasis. Our results demonstrated that NKX6.1 functions as a tumor suppressor partly by repressing EMT and enhancing chemosensitivity in CRC, making it a potential therapeutic target.

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Section: Introductionmentioning

confidence: 99%

NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer

Chung

Lee

et al. 2020

IJMS

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“…A retrospective clinical analysis reports better chemotherapy treatment response in Nm23-expressing tumors [202]. A recent study links a higher promoter methylation status of the metastasis suppressor NK6 homeobox 1 (NKX6.1) resulting in reduced expression, with a less favorable prognosis of stage II CRC patients after receiving adjuvant chemotherapy [203]. This points to a promising strategy to re-express MSGs in cancer cells.…”

Section: Metastasis Suppressors-natural Borne Inhibitorsmentioning

confidence: 99%

Small Ones to Fight a Big Problem—Intervention of Cancer Metastasis by Small Molecules

Kobelt

Dahlmann

Dumbani

et al. 2020

Cancers

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Metastasis represents the most lethal attribute of cancer and critically limits successful therapies in many tumor entities. The clinical need is defined by the fact that all cancer patients, who have or who will develop distant metastasis, will experience shorter survival. Thus, the ultimate goal in cancer therapy is the restriction of solid cancer metastasis by novel molecularly targeted small molecule based therapies. Biomarkers identifying cancer patients at high risk for metastasis and simultaneously acting as key drivers for metastasis are extremely desired. Clinical interventions targeting these key molecules will result in high efficiency in metastasis intervention. In result of this, personalized tailored interventions for restriction and prevention of cancer progression and metastasis will improve patient survival. This review defines crucial biological steps of the metastatic cascade, such as cell dissemination, migration and invasion as well as the action of metastasis suppressors. Targeting these biological steps with tailored therapeutic strategies of intervention or even prevention of metastasis using a wide range of small molecules will be discussed.

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“…The vast majority of genes that are found to be hypermethylated are associated with a worse response to therapy. CRC patients with hypermethylated NKX6.1 , TFAP2E , IGFBP3 , and HYAL2 genes did not profit from 5-FU-based chemotherapy [ 173 , 174 , 175 , 176 ].…”

Section: Clinical Applications Of Dna Methylation Profilingmentioning

confidence: 99%

Methylation-Based Therapies for Colorectal Cancer

Červená

Siskova

Büchler

et al. 2020

Cells

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Colorectal carcinogenesis (CRC) is caused by the gradual long-term accumulation of both genetic and epigenetic changes. Recently, epigenetic alterations have been included in the classification of the CRC molecular subtype, and this points out their prognostic impact. As epigenetic modifications are reversible, they may represent relevant therapeutic targets. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), regulates gene expression. For many years, the deregulation of DNA methylation has been considered to play a substantial part in CRC etiology and evolution. Despite considerable advances in CRC treatment, patient therapy response persists as limited, and their profit from systemic therapies are often hampered by the introduction of chemoresistance. In addition, inter-individual changes in therapy response in CRC patients can arise from their specific (epi)genetic compositions. In this review article, we summarize the options of CRC treatment based on DNA methylation status for their predictive value. This review also includes the therapy outcomes based on the patient’s methylation status in CRC patients. In addition, the current challenge of research is to develop therapeutic inhibitors of DNMT. Based on the essential role of DNA methylation in CRC development, the application of DNMT inhibitors was recently proposed for the treatment of CRC patients, especially in patients with DNA hypermethylation.

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NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy

Cited by 19 publications

References 55 publications

NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer

NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer

Small Ones to Fight a Big Problem—Intervention of Cancer Metastasis by Small Molecules

Methylation-Based Therapies for Colorectal Cancer

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