Metastasis model of tumor deposit in colorectal cancer based on phylogenetic tree.

Abstract

e15549 Background: Colorectal cancer(CRC) is often accompanied by tumor deposit(TD) metastasis, and TD status was only adressed in N1c staging in the TNM staging for CRC. However, TD states are very complex and diverse, including quantity, morphology, and biological behavior. The correlation between TD and clinical prognosis is far more complicated and needs to be discussed in more dimensions. At present, there are no reports of TD research from the genetic perspective. In this study, the phylogenetic tree approach was used to explore the metastasis pattern of TD, which might lay a foundation for better understanding its clinical significance. Methods: Poly-G was used to sequence multiple sections (n = 427) of normal tissue, primary tumor, TD, positive lymph node, and distant metastasis from 25 patients. Then, using the poly-G genotype to calculated the genetic distance between tumor and normal tissue and built the phylogenetic tree. We use root diversity score (RDS) index to reflect the intratumor heterogeneity of TDs. The evolutionary connection and clone origin between TD and paired samples was evaluated using a phylogenetic tree and RDS index. Results: A total of 427 samples from 25 patients were included, including 171 primary tumor (40.0%), 94 positive lymph nodes (22.0%), 110 tumor deposits (25.8%), 28 liver metastases (6.6%), 4 lung metastases (0.9%), and 20 peritoneal metastases (4.7%). There were 43 (39.1%) TDs with envelope and 67 (60.9%) TDs with irregular morphology, according to pathological morphology. A phylogenetic tree based on migration patterns and clonal origins was used to highlight the differences between envelope-TDs and irregular-TDs. The genetic distance between envelope-TDs and positive lymph nodes appeared to be less, and they were more likely to derive from the same source, but the genetic distance between irregular-TDs and positive lymph nodes was larger (P < 0.05). Envelope-TDs had a sequential metastatic model that was consistent with positive lymph nodes. Unlike envelope-TDs, irregular-TDs tend to show more complex biological characteristics, such as nerve and vascular invasion, resulting in a more convoluted evolutionary relationship in the phylogenetic tree. Conclusions: Our findings provide genetic evidence for TD metastatic model, which has to be supported in future studies to ameliorate CRC TNM staging.