RESUMEN
BACKGROUND: Circulating tumor DNA (ctDNA) has been recognized as a promising biomarker for colorectal cancer (CRC) early diagnosis and postoperative monitoring. However, we hypothesize that the clinical value of ctDNA sequencing may differ for colon cancer (CC) and rectal cancer (RC). METHODS: Forty-three patients with primary CRC were prospectively enrolled. Tumor tissue samples, paired preoperative plasma samples and a series of postoperative plasma samples were obtained. Mutations in each sample were identified and compared. RESULTS: For 73.0% patients, at least one concordant mutation was detected in both tumor tissue DNA and paired preoperative ctDNA. The mutation concordance rate were higher in CC patients compared to RC patients (92.3% vs 45.5%; p= 0.004). For early stage patients, the mutation concordance rate was 72.7%. The recurrence rate was 33.3% for patients with postoperative ctDNA positive mutations, and 3.4% for patients with negative ctDNA (HR 10.767; 95% CI 1.1-103.8; p= 0.040). CONCLUSION: Liquid biopsy via ctDNA sequencing has great potential for the early detection and postoperative monitoring of CRC. The DNA of CC tissues is more likely to be released into blood than the DNA of RC tissues. This should be considered when diagnosing CRC patients with ctDNA sequencing technology.
Asunto(s)
Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/sangre , Neoplasias del Colon/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias del Recto/diagnóstico , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/aislamiento & purificación , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/aislamiento & purificación , Neoplasias del Colon/sangre , Neoplasias del Colon/genética , Neoplasias del Colon/cirugía , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Biopsia Líquida/métodos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Recurrencia Local de Neoplasia/genética , Pronóstico , Estudios Prospectivos , Neoplasias del Recto/sangre , Neoplasias del Recto/genética , Neoplasias del Recto/cirugíaRESUMEN
Seahorses have a specialized morphology that includes a toothless tubular mouth, a body covered with bony plates, a male brood pouch, and the absence of caudal and pelvic fins. Here we report the sequencing and de novo assembly of the genome of the tiger tail seahorse, Hippocampus comes. Comparative genomic analysis identifies higher protein and nucleotide evolutionary rates in H. comes compared with other teleost fish genomes. We identified an astacin metalloprotease gene family that has undergone expansion and is highly expressed in the male brood pouch. We also find that the H. comes genome lacks enamel matrix protein-coding proline/glutamine-rich secretory calcium-binding phosphoprotein genes, which might have led to the loss of mineralized teeth. tbx4, a regulator of hindlimb development, is also not found in H. comes genome. Knockout of tbx4 in zebrafish showed a 'pelvic fin-loss' phenotype similar to that of seahorses.
Asunto(s)
Evolución Biológica , Proteínas de Peces/genética , Genoma/genética , Smegmamorpha/anatomía & histología , Smegmamorpha/genética , Aletas de Animales/anatomía & histología , Aletas de Animales/metabolismo , Animales , Secuencia Conservada/genética , Proteínas de Peces/deficiencia , Eliminación de Gen , Genómica , Miembro Posterior/anatomía & histología , Miembro Posterior/metabolismo , Masculino , Anotación de Secuencia Molecular , Familia de Multigenes/genética , Tasa de Mutación , Filogenia , Reproducción/fisiología , Proteínas de Dominio T Box/deficiencia , Proteínas de Dominio T Box/genética , Factores de Tiempo , Proteínas de Pez Cebra/deficiencia , Proteínas de Pez Cebra/genéticaRESUMEN
The major histocompatibility complex (MHC) genes are crucial in the adaptive immune system, and the gene duplication of MHC in animals can generally result in immune flexibility. In this study, we found that the lined seahorse (Hippocampus erectus) has only one gene copy number (GCN) of MHC IIα and IIß, which is different from that in other teleosts. Together with the lack of spleen and gut-associated lymphatic tissue (GALT), the seahorse may be referred to as having a partial but natural "immunodeficiency". Highly variable amino acid residues were found in the IIα and IIß domains, especially in the α1 and ß1 domains with 9.62% and 8.43% allelic variation, respectively. Site models revealed seven and ten positively selected positions in the α1 and ß1 domains, respectively. Real-time PCR experiments showed high expression levels of the MHC II genes in intestine (In), gill (Gi) and trunk kidney (TK) and medium in muscle (Mu) and brood pouch (BP), and the expression levels were significantly up-regulated after bacterial infection. Specially, relative higher expression level of both MHC IIα and IIß was found in Mu and BP when compared with other fish species, in which MHC II is expressed negligibly in Mu. These results indicate that apart from TK, Gi and In, MU and BP play an important role in the immune response against pathogens in the seahorse. In conclusion, high allelic variation and strong positive selection in PBR and relative higher expression in MU and BP are speculated to partly compensate for the immunodeficiency.
