Alternations in genes expression of pathway signaling in esophageal tissue with atresia: results of expression microarray profiling

Abstract

Esophageal atresia (EA) is a congenital defect of the esophagus involving the interruption of the esophagus with or without connection to the trachea (tracheoesophageal fistula [TEF]). EA/TEF may occur as an isolated anomaly, may be part of a complex of congenital defects (syndromic), or may develop within the context of a known syndrome or association. The molecular mechanisms underlying the development of EA are poorly understood. It is supposed that a combination of multigenic factors and epigenetic modification of genes play a role in its etiology. The aim of our work was to assess the human gene expression microarray study in esophageal tissue samples. Total RNA was extracted from 26 lower pouches of esophageal tissue collected during thoracoscopic EA repair in neonates with the isolated (IEA) and the syndromic form (SEA). We identified 787 downregulated and 841 upregulated transcripts between SEA and controls, and about 817 downregulated and 765 upregulated probes between IEA and controls. Fifty percent of these genes showed differential expression specific for either IEA or SEA. Functional pathway analysis revealed substantial enrichment for Wnt and Sonic hedgehog, as well as cytokine and chemokine signaling pathways. Moreover, we performed reverse transcription polymerase chain reaction study in a group of SHH and Wnt pathways genes with differential expression in microarray profiling to confirm the microarray expression results. We verified the altered expression in SFRP2 gene from the Wnt pathway as well as SHH, GLI1, GLI2, and GLI3 from the Sonic hedgehog pathway. The results suggest an important role of these pathways and genes for EA/TEF etiology.

The Impact of Congenital Esophageal Atresia on the Family Functioning

“…tracheo-esophageal fistula (TEF) (Clark, 1999). All infants with EA need surgery during their first days of life, and primary surgery with esophageal anastomoses is preferable treatment (Śmigiel et al, 2015;Tovar & Fragoso, 2011). Although survival rates have improved up to 95%, EA is a cause of long-term esophageal and respiratory complications persisting into adulthood (Ijsselstijn, van Beelen, & Wijnen, 2013): dysphagia and gastroesophageal reflux disease (GOR) (Pedersen et al, 2013), feeding difficulties (Menzies, Hughes, Leach, Belessis, & Krishnan, 2017), chronic cough, wheezing, and recurrent airway infections (Porcaro et al, 2017).…”

Congenital Esophageal Atresia—Surgical Treatment Results in the Context of Quality of Life

“…In the remaining 55% of patients, EA coexists with other defects (syndromic form), which together may form a genetic syndrome or association. 4,5 The pathogenesis of EA is poorly understood, but it is thought that this defect arise due to the errors in the embryonic development. 5 It is supposed that a combination of multigenic factors and epigenetic modification of genes plays a role in its etiology.…”

“…4,5 The pathogenesis of EA is poorly understood, but it is thought that this defect arise due to the errors in the embryonic development. 5 It is supposed that a combination of multigenic factors and epigenetic modification of genes plays a role in its etiology. 6 The fundamental morphogenetic process appears to be a rearrangement of the proximal foregut into separate respiratory (ventral) and gastrointestinal (dorsal) tubes.…”

“…7 Progress in pediatric surgery in recent decades has reduced the mortality and the incidence of postoperative complications, but the treatment of congenital EA, particularly in the syndromic form, still remains a challenge for many medical specialties. [5][6][7] Most infants born with EA/TEF do grow up to lead essentially normal adult life; however, many continue to have medical issues as a result of the disorder. Most of the research in the field of EA is focused on diagnostic problems and surgery.…”

Pre- and Postnatal Surgery, Most Common Conditions, Diagnosis and Treatment

“…It usually occurs in the products of conception of young women. Polyhydramnios can be found during the prenatal visit, which should be the most important warning sign [13,14]. In pediatric surgery, it is said that sialorrhea in the newborn child is equivalent to an esophageal atresia until proven otherwise.…”