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Recent Research Progress
The esophageal cancer-associated gene 4 (ECRG4), also known as C2orf40, is located on chromosome 2q12.2. ECRG4 is a tumor suppressor gene that was originally identified and cloned from human esophageal epithelial cells in 1998. ECRG4 is widely expressed in normal human tissues. It has been reported that ECRG4 is expressed at low or undetectable levels in various malignant tumor tissues and cell lines, and the expression level of ECRG4 is closely related to tumor proliferation and apoptosis.
ECRG4 and renal cancer
Recent studies indicated that expression of ECRG4 was down-regulated in renal cell lines and renal cancer tissues. ECRG4 expression was significantly associated with histological grade of the tumor, primary tumor stage and distant metastasis. Low expression of ECRG4 is an independent prognostic indicator for survival in patients with renal cancer. Silencing of ECRG4 expression in renal cell lines is associated with promoter methylation. Furthermore, ectopic expression of ECRG4 significantly inhibited cell proliferation and invasion in renal cancer cell lines. These results indicate that ECRG4 is often silenced by methylation of the promoter in renal cell carcinoma. ECRG4 can be a tumor suppressor in kidney cancer and is used as a prognostic marker.
ECRG4 and Laryngeal cancer
Laryngeal cancer is a malignant tumor that originates in the epithelial tissue of the laryngeal mucosa. Recently, the study found that ECRG4 inhibited the growth of laryngeal cancer cells through arresting cells in the G0 / G1 phase and delaying cell cycle from G0 / G1 phase to S phase and G2 / M phase. In addition, overexpression of ECRG4 activated caspase-3 and poly ADP-ribose polymerase (PARP), and ultimately induces apoptosis by up-regulating the expression of the pro-apoptotic protein Bax and down-regulating the expression of the anti-apoptotic protein Bcl-2. Hence, overexpression of ECRG4 may become an effective gene therapy strategy for the treatment of laryngeal cancer.
ECRG4 and NPC
Human nasopharyngeal carcinoma (NPC) is a malignant type of cancer with an increasing incidence. However, to date, molecular biomarkers with powerful diagnostic impacts and major therapeutic prospects have remained elusive. Recently, studies have found that expression of ECRG4 was noted in primary NPC tumors relative to normal tissues, and this decreased expression was found to be associated with its promoter methylation status. Yanjie You et al. found that ECRG4 promoter hypermethylation occurred frequently in primary NPC specimens, and its concomitant detection in peripheral blood samples showed high sensitivity and specificity for cancer diagnosis and monitoring.
ECRG4 and BC
The poor prognosis of breast cancer (BC) is largely due to early and frequent metastasis. So far, the mechanism of BC metastasis is unclear, and the appropriate molecular markers for BC metastasis and progression remain elusive. ECRG4 protein expression was significantly reduced in BC tissues compared to non-cancerous tissues. Recent studies have shown that lack of ECRG4 protein expression may lead to metastatic potential and progression of BC. In addition, ECRG4 protein expression has a significant impact on patient survival and, therefore, can serve as an independent prognostic factor.
ECRG4 and ESCC
Esophageal squamous cell carcinoma (ESCC) is a highly invasive and clinically challenging cancer. Despite advances in clinically integrated therapy, the prognosis of ESCC remains poor due to its diffuse and aggressive nature. ECRG4 is a candidate tumor suppressor gene and is an independent prognostic factor of ESCC. Overexpression of ECRG4 gene inhibits proliferation and invasion of tumor cells in ESCC.
Taken together, studies have shown that ECRG4 can effectively inhibit the proliferation of tumor cells and induce apoptosis. In addition, there are data showing that ECRG4 may not only contribute to prognosis prediction, but may also provide new tailored treatment options. Consequently, further research on ECRG4 is undoubtedly necessary and valuable.
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