Release date: 2018-02-26
Primary liver cancer, known as the cancer king, metastasis and recurrence is a key factor affecting the survival rate, but also a difficult and hot spot in cancer research. The lung is one of the most common sites of liver metastasis. How does lung metastasis of liver cancer occur? Professor Xia Jinglin from Zhongshan Hospital affiliated to Fudan University and researcher Chen Luonan from the Institute of Cell Biochemistry of the Chinese Academy of Sciences led a team of four years of research, and finally achieved a breakthrough in the mechanism of liver metastasis of liver cancer: the first successful use of dynamic network markers (DNB) method to screen and map out “lung cancer lungs†Early warning network signal diagram before the transfer occurs. According to this figure, dynamic changes at different stages of the disease can be observed. Related research was published in the latest international core journal Nature Communication. Expert evaluation, the results will have important clinical value for the study of liver cancer lung metastasis.
Professor Xia Jinglin said that the process and mechanism of lung cancer metastasis in the international medical community are not clear. Is lung metastasis of primary liver cancer progressive? Or is it suddenly changing? Is there a critical critical phase or an early warning phase? Can I find early warning signals for the critical phase of prediction for early diagnosis? The team conducted an in-depth study of this.
The expression level of CALML3 and its interacting genes is dynamic during the process of liver metastasis of liver cancer.
Xia Jinglin and Chen Luonan led the team to use the high-transfer human liver cancer nude mouse model to detect the gene changes in different stages of liver cancer lung metastasis using a genome-wide transcriptional expression profile chip, and found the tumor in the original dynamic network biomarker (DNB) method. The third week after transplantation was the critical stage of liver metastasis of liver cancer, and the DNB core gene with early warning value for liver metastasis of liver cancer was successfully identified and screened.
Schematic diagram of the development process and critical stage of liver metastasis of liver cancer.
In order to further explore the mechanism of the role of DNB core gene in promoting liver metastasis, the research team further found the gene "CALML3" which plays a key role in DNB. Finally, based on the dynamic changes in the expression levels of CALML3 and its interacting genes, the research team mapped out early warning network signals of “before liver cancer lung metastasisâ€. This picture clearly shows the most change before and after the third week (ie, early warning stage). obvious. In addition, through the nude blood cell tumor cell test in nude mice, it was found that a small amount of cancer cells appeared in the blood samples at the 4th week, indicating that cancer metastasis had occurred. This further confirms that the third week is the critical (warning) stage before the occurrence of lung metastasis, and reveals the development of lung metastasis of primary liver cancer, which is not a gradual change, but a sudden change point.
In order to verify the role of the key gene "CALML3" in DNB in ​​lung metastasis of liver cancer and the clinical prognostic value, the research team found in vitro and in vivo that CALML3 significantly inhibited liver cancer growth and lung metastasis. Of the 270 patients with liver cancer resection, 114 patients with positive CALML3 expression, positive expression, the survival rate was significantly higher than the other 156 patients with negative CALML3 expression, and the positive rate of CALML3 expression was significantly lower than those with negative expression.
Xia Jinglin told the Liberation Daily and Shangguan journalists that the above study found for the first time the inhibitory effect of CALML3 on liver cancer growth and lung metastasis. As a cancer suppressor gene, CALML3 may become a new early marker for liver cancer lung metastasis and a new target for inhibiting liver cancer growth and lung metastasis.
Source: Shangguan News
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