RESUMO
BACKGROUND: Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. METHODS: We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. RESULTS: Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial-mesenchymal transition (EMT). CONCLUSIONS: In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination.
Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Peritoneais/genética , Peritônio , RNA , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
BACKGROUND: Child undernutrition, commonly measured by growth failure, is associated with functional disadvantages later in life. AIMS: To assess relationships between child growth and women's educational achievement (EA). STUDY DESIGN AND SUBJECTS: Women from four ladino Guatemalan villages were measured as children (1969-1977) and again at ages 20-29 years (1996-1999). The anthropometric measurements analyzed were weight, length, and head circumference (HC) at birth and 2 years and height at adulthood. Sample sizes were 120 at birth, 133 at 2 years, and 145 at adulthood; 108 cases had data at all three points. OUTCOME MEASURES: Women's EA was computed based on five educational tests and was categorized into quintiles. Analysis was based on a proportional odds model. Generalized estimating equations were used to account for sibling clustering. Multiple Stage Least Squares analyses were used to assess the relative importance of birth size and of early (birth to age 2 years) and late postnatal growth (2 years to adulthood). RESULTS: Size at 2 years (HC and length) but no indicator at birth was positively associated with women's EA. Schooling was a strong, positive predictor of women's EA (odds ratio (OR)=13.7, 95% confidence interval (CI) [6.1, 30.6]). Early postnatal growth but not birth size or late postnatal growth was associated with women's EA (OR with 1 standard deviation (S.D.) increment in length=1.5, 95% CI [1.05, 2.2]). CONCLUSIONS: Growth in length and HC from birth to 2 years of age, but not birth size or growth after 2 years, is an important predictor of women's EA.
Assuntos
Envelhecimento/fisiologia , Peso ao Nascer/fisiologia , Estatura/fisiologia , Escolaridade , Recém-Nascido/crescimento & desenvolvimento , Aumento de Peso/fisiologia , Adulto , Feminino , Seguimentos , Guatemala , Humanos , Razão de ChancesRESUMO
OBJECTIVE: Malnutrition during early childhood has been suggested to cause functional disadvantages in adults, including reduced intelligence and lower educational achievement (EA). We assessed the effects of improved nutrition in early life on the EA of women in 4 rural Guatemalan villages. METHODS: The study sample comprised 130 female singletons exposed to either Atole (53%, 91 kcal and 6.4 g protein/100 mL) or Fresco (47%, 33 kcal/100 mL, no protein) during the prenatal period and the first 2 years of life. EA was assessed at the ages of 22 to 29 years by knowledge, numeracy, and several reading tests. A summary measure of EA was computed based on 5 tests, and outcome variables were categorized into quintiles. Analysis was based on a proportional odds model. Generalized estimating equations were used to account for sibling clustering. RESULTS: Overall, 36.2% of women completed primary school. Women exposed to Atole had better EA than those exposed to Fresco (odds ratio [OR]: 2.8; 95% confidence interval [CI], 1.4, 5.4), with a significant treatment-by-schooling interaction. Atole was not associated with EA (OR: 1.5; 95% CI: 0.7, 3.2) among women who did not complete primary school, whereas among those who completed primary school, Atole was associated with improved EA (OR: 13.7; 95% CI: 3.7, 50.8). CONCLUSIONS: We conclude that better nutrition during early childhood improved adult EA, but only among children who completed primary school.