HOXC10 upregulation confers resistance to chemoradiotherapy in ESCC tumor cells and predicts poor prognosis.
Daqin SuoZi-Feng WangLei LiQingyun ChenTingting ZengRan-Yi LiuJingping YunXin-Yuan GuanYan LiPublished in: Oncogene (2020)
Esophageal squamous cell carcinoma (ESCC) is a malignant disease and is a common cause of death in China. By performing an integrative study investigating public databases and clinical samples collected by our group, we found that HOXC10 (homeobox C10) is upregulated in ESCC tumor tissues compared with nontumor tissues and that the upregulation of HOXC10 is correlated with the poor prognosis of patients with ESCC. The enforced expression of HOXC10 promoted ESCC cell proliferation in vitro and in vivo. Our study revealed that HOXC10 could bind the promoter region of human Erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) and activate the PI3K/AKT pathway. In addition, by immunoprecipitation and mass spectrometry analysis, we found that HOXC10 could bind X-ray repair cross complementing 6 (Ku70) and accelerate the DNA repair mechanism via the nonhomologous end-joining (NHEJ) pathway. We further evaluated HOXC10 expression in ESCC patients receiving adjuvant radiotherapy or platinum-based chemotherapy. The results demonstrate that HOXC10 upregulation predicts the poor prognosis of ESCC patients receiving adjuvant radiotherapy or chemotherapy. Our study reveals that HOXC10 upregulation reflects the poor prognosis of ESCC patients and directs the selection of postoperative therapy regimens.
Keyphrases
- poor prognosis
- long non coding rna
- tyrosine kinase
- dna repair
- locally advanced
- early stage
- cell proliferation
- mass spectrometry
- healthcare
- radiation therapy
- high resolution
- dna damage
- end stage renal disease
- endothelial cells
- squamous cell carcinoma
- ejection fraction
- chronic kidney disease
- epidermal growth factor receptor
- newly diagnosed
- stem cells
- mental health
- machine learning
- oxidative stress
- peritoneal dialysis
- ms ms
- bone marrow
- single cell
- deep learning
- drug induced
- cell therapy
- patient reported outcomes