Cheng Cai

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

Objective: This study was performed to identify a reasonable cutoff age for defining older patients with colorectal cancer (CRC) and to examine whether old age was related with increased colorectal cancer-specific death (CSD) and poor colorectal cancer-specific survival (CSS).Methods: A total of 76,858 eligible patients from the surveillance, epidemiology, and end results (SEER) database were included in this study. The Cox proportional hazard regression model and the Chow test were used to determine a suitable cutoff age for defining the older group. Furthermore, a propensity score matching analysis was performed to adjust for heterogeneity between groups. A competing risk regression model was used to explore the impact of age on CSD and non-colorectal cancer-specific death (non-CSD). Kaplan–Meier survival curves were plotted to compare CSS between groups. Also, a Cox regression model was used to validate the results. External validation was performed on data from 1998 to 2003 retrieved from the SEER database.Results: Based on a cutoff age of 70 years, the examined cohort of patients was classified into a younger group (n= 51,915, n= 24,943, ≥70 years of old). Compared with younger patients, older patients were more likely to have fewer lymph nodes sampled and were less likely to receive chemotherapy and radiotherapy. When adjusted for other covariates, age-dependent differences of 5-year CSD and 5-year non-CSD were significant in the younger and older groups (15.84% and 22.42%,P< 0.001; 5.21% and 14.21%,P< 0.001). Also an age of ≥70 years remained associated with worse CSS comparing with younger group (subdistribution hazard ratio, 1.51 95% confidence interval (CI) [1.45–1.57],P< 0.001). The Cox regression model as a sensitivity analysis had a similar result. External validation also supported an age of 70 years as a suitable cutoff, and this older group was associated with having reduced CSS and increased CSD.Conclusions: A total of 70 is a suitable cutoff age to define those considered as having elderly CRC. Elderly CRC was associated with not only increased non-CSD but also with increased CSD. Further research is needed to provide evidence of whether cases of elderly CRC should receive stronger treatment if possible.