Nat Commu: Colorectal near-end lymph node metastasis, from near to far?

Nature Communications published a research paper by the Center for Frontier Innovation in Biomedical Sciences (BIOPIC) at Peking University and the Bai Fan Group at the School of Life Sciences: Mapping the Spreading Routes of the lymphatic metastases in the human colorectal (humanpath study of theof colorectal cancer to the lymphatic system)according to the latest WHO statistics, colorectal cancer is the third highest incidence rate in the world, the second highest fatality rate of cancerThe metastasis of primary colorectal cancer to near-end lymphatic system and distant organ metastasis is an important cause of death, but whether the occurrence of far-end organ metastasis depends on the formation of near-end lymphatic metastasis is a controversial issue, and the transfer path of near-end lymph nodes is not revealed due to the lack of effective research methodsin this work, the researchers strictly screened into the group of research objects, comprehensive fine sampling, innovative biological information analysis methods, the composition of cancer lesions to analyze, reconstruction of colorectal cancer in the time, space scale of metastasis history and pathFirst, the researchers took multi-point samples of in situ lesions and liver metastasis in 10 colorectal cancer cases in the group to ensure that the samples were representative of the cancer ousnta, and the lymph node metastasis was fully sifted into three stations according to their physical location, namely, paracollics ( Intermediate , Central) lymph node lesions , using microcutting to extract tumor tissue (Figure 1)Figure 1: Patient swed (a) and sampling strategy (b, c) schematic, after sequencing the sample with a high depth exome group, using a variety of bioinformatics methods to high-precision resolution of the cloning ratio of the cancer stove, using the pigeon nest principle to reconstruct the clone composition of the sample, build a clone evolutionary tree, and then judge the history of the development and metastasis in colorectal cancer patients, and finally determine the stable, maximum probability of tumor metastasis network (Figure 2)Figure 2: Restoring clone composition (a), cloning history (b), mapping tumor metastasis (c,d)researchers found that in the patients enrolled, known colorectal cancer-driven mutations (such as APC, KRAS, TP53 mutations, etc., mostly occurred in the early stages, in all cancer cellsIn all the transfer events, monoclonal transfer (monoclonal seeding) and multiclonal transfer (multiclonal transfer) were 26.2% and 73.8% respectively, and multi-clone transfer was the main form of colorectal cancer metastasisBy restoring the transfer path of colorectal cancer patients, the researchers found that 37.7 percent of the metastasis events did not come directly from the spread of the primary lesions, but from the retransfer of the metastases-to-metastasesIt is worth noting that the retransfer capacity of different lymph node lesions varied greatly, and in 5 cases, the study found lymph node metastasis with high metastasis potentialIt is interesting to note that lymph node transfer does not spread in a simple order of near and far, but rather that there are a large number of cross-station "jump" transfersFor distant liver metastasis, it can either originate from the primary lesions or from the lymph node metastasis or from the metastasis that already exists on the liver, and in case Patient_9, two liver transfer lesions are from the secondary transfer of in situ seeding and lymph node transfer (Figure 3), indicating that the source of colorectal cancer far-end metastasis cannot be generalizedThis work makes innovative use of bioinformatics methods to fine-tune the metastasis of colorectal cancer patients on the time and space scale for the first time, and provides direct answers to the important problems related to colorectal cancer metastasisFigure 3: Path reduction and 3 types of metastasis (c, d, e)
in patients with colorectal cancer (a), chinese Academy of Medicine, Oncology Hospital of the Chinese Academy of Medical Sciences, Beijing Concord Medical College,Ph.Dstudents Zhang Lin, Xu Tianlei and Yan Liang, assistant researcher Xue Ruidong of the Cancer Conversion Research Center of Peking University First Hospital are co-first authors, and Professor Zhang Haizen of Oncology, National Cancer Center, Chinese Academy of Medical Sciences, and Bai Fan, Researcher of bioPIC and School of Life Sciences of Peking University, are the authors of the communication