New results in clinical studies of liquid biopsy: CTM and interstitial CTC detected in patients with colorectal cancer predict a worse prognosis

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Professor Zhang Tao from the Cancer Center of Wuhan Union Hospital has conducted a five-year clinical follow-up study on colorectal cancer patients undergoing chemotherapy through circulating tumor cell detection technology. The study found that the detection of CTM and Vimentin-positive CTC in peripheral blood of patients with colorectal cancer undergoing chemotherapy compared to the detection of a single CTC or the detection of a CK-positive CTC, indicating a shorter progression-free survival ( PFS) and overall survival (OS), while CTC/CTM with EMT was significantly associated with another new prognostic factor, KIAA1199 (cell migration inducing protein). The research is the result of a collaborative study between Professor Zhang Tao's team and Zhiyou Medical Research and Development Department.

Professor Zhang Tao from the Cancer Center of Wuhan Union Hospital, through the CTCBIOPSY® platform, performed CTC and CTM count studies and molecular typing studies on 98 patients with colorectal cancer who underwent 2-6 cycles of chemotherapy, and followed up for 5 years.

The study found that the detection rates of CTC and CTM in 5 mL of peripheral blood of these 98 subjects were 48.9% (48/98) and 18.3% (18/98), respectively. Further studies found that the detection of CTC was significantly associated with lymphatic invasion (P=0.049), TNM stage (P=0.023), and serum CEA (P=0.014). After 5 years of follow-up, Professor Zhang Tao found that CTC detection was an independent prognostic factor for chemotherapy in patients with advanced colorectal cancer (P<0.05). At the same time, CTM-positive patients had shorter PFS and OS than CTC-positive patients. The results fully reflect that the microtubules of circulating tumor cells aggregated into a group are more threatening and more representative of the malignant degree of tumor development.

Professor Zhang Tao also conducted molecular typing studies on CTCs in 32 CTC-positive patients. The captured CTC/CTM was divided into four molecular subtypes by immunofluorescence technique (IF): 1) CK+Vimentin+ CTM; 2) CK-Vimentin+ CTM; 3) CK-Vimentin+ CTC; 4) CK+Vimentin-CTC (see figure below). By following up on follow-up of different molecular subtypes of CTC/CTM positive patients, the investigators found that the positive CTC/CTM detective of Vimentin+ had a significantly worse prognosis than the CTC positive tester of CK+ (PFS, 6 months vs 11 months) , P = 0.0314; OS, 11 months vs 20 months, P = 0.0147). This result verifies the view that CTC or CTM enhances the immune escape ability of tumor cells and the viability in peripheral blood by undergoing a transition of interstitialization. The study also confirmed that further molecular typing for CTC/CTM can better predict the prognosis of patients with colorectal cancer.

The results of the study in January 2017 were entitled "Circulating tumor microemboli (CTM) and vimentin + circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy" in the internationally renowned clinical magazine "Cancer" Cell International (2016 IF=2.884) was published.

(This figure is quoted from Zhang et al. Cancer Cell Int, 2017, 17:6)

(This figure is quoted from Zhang et al. Cancer Cell Int, 2017, 17:6)

Another research project by Professor Zhang Tao involving CTC/CTM was also received by the internationally renowned magazine International Journal of Cancer (2016 IF=5.531) and will be published soon. The study found a cell migration-inducing protein, KIAA1199. The study found that this protein in cancer patients can promote EMT conversion of cancer cells, promote cancer invasion and distant metastasis, interference with the expression of this protein can effectively reduce the metastasis of cancer cells. The high expression of KIAA1199 in the lesions of patients with colorectal cancer indicates a worse prognosis. At the same time, CTC detection by CTCBIOPSY® platform revealed that KIAA1199 high expression was significantly correlated with interstitial CTC/CTM, which explains from a molecular perspective why the detection of interstitial CTC/CTM is predictive of worse for patients with advanced colorectal cancer. The prognosis.

(The figure is provided by the original author)

The above study is the first to report the clinical study of the relationship between the detection of interstitial circulating tumor cells and the prognosis of patients with colorectal cancer. It is also the first internationally reported clinical study of the relationship between the detection of microtubules in patients with colorectal cancer and the prognosis of patients with colorectal cancer.

Dr. Zhou Pengfei, the inventor of the CTCBIOPSY® detection platform, commented on the study: “Recurrence and metastasis of tumors is the leading cause of failure in colon cancer treatment. Professor Zhang Tao’s series of clinical studies have shown that there are cancer stem cell characteristics in the blood of colon cancer patients. Circulating tumor cells, the appearance of these tumor cells is closely related to the patient's metastasis and prognosis. Professor Zhang Tao's research reveals a new mechanism of tumor metastasis, which provides a powerful basis for future molecular targeted therapy related to tumor metastasis. ”

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Attached to Professor Zhang Tao personal and team profile:

Zhang Tao, MD, professor, chief physician, doctoral tutor. Deputy Director of the Cancer Center of the Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, deputy director of the Department of Oncology. Professor Zhang Tao's research group has been committed to research on cancer stem cells and tumor biotherapy for many years. In recent years, he has undertaken a total of 7 national natural science funds and provincial and ministerial level projects. His research results have published more than 20 SCI papers, respectively. "Blood", "Cancer Research", "Journal of Immunotherapy" and other magazines provide a theoretical basis and practical basis for targeted therapy, enhanced efficacy and biological treatment of malignant tumors.

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