Association of sonic hedgehog signaling pathway genes IHH, BOC, RAB23a and MIR195-5p, MIR509-3-5p, MIR6738-3p with gastric cancer stage

• Published in: Scientific reports Vol. 11; no. 1; p. 7471
• Main Authors: Fattahi, Sadegh, Nikbakhsh, Novin, Ranaei, Mohammad, Sabour, Davood, Akhavan-Niaki, Haleh
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-04-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1504/1829; 692/53; Aged; Biomarkers; Biomarkers, Tumor - genetics; Developmental stages; Embryogenesis; Embryonic growth stage; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; Hedgehog protein; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Humanities and Social Sciences; Humans; Immunoglobulin G - genetics; Immunoglobulin G - metabolism; Infections; Intracellular signalling; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; multidisciplinary; Neoplasm Staging; Pluripotency; Precision medicine; Public health; rab GTP-Binding Proteins - genetics; rab GTP-Binding Proteins - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; ROC Curve; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - genetics; Stem cells; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach Neoplasms - virology; Therapeutic targets; Tumorigenesis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-86946-0

Gastric cancer is the leading cause of cancer-related mortality worldwide. Given the importance of gastric cancer in public health, identifying biomarkers associated with disease onset is an important part of precision medicine. The hedgehog signaling pathway is considered as one of the most significant widespread pathways of intracellular signaling in the early events of embryonic development. This pathway contributes also to the maintenance of pluripotency of cancer stem cells pluripotency. In this study, we analyzed the expression levels of sonic hedgehog (Shh) signaling pathway genes IHH, BOC, RAB23a and their regulatory miRNAs including MIR-195-5p, MIR-509-3-5p, MIR-6738-3p in gastric cancer patients. In addition, the impact of infection status on the expression level of those genes and their regulatory miRNAs was investigated. One hundred samples taken from 50 gastric cancer patients (50 tumoral tissues and their adjacent non-tumoral counterparts) were included in this study. There was a significant difference in all studied genes and miRNAs in tumoral tissues in comparison with their adjacent non-tumoral counterparts. The lower expression of IHH, BOC, RAB23, miR-195-5p, and miR-6738-3p was significantly associated with more advanced cancer stage. Additionally, IHH upregulation was significantly associated with CMV infection (
P
 < 0.001). Also, receiver operating characteristic (ROC) curve analysis indicated that mir-195 was significantly related to several clinicopathological features including tumor stage, grade, age, gender, and infection status of gastric cancer and can be considered as a potential diagnostic biomarker for gastric cancer. This study confirms the important role of Shh signaling pathway genes in gastric cancer tumorigenesis and their potential as novel molecular biomarkers and therapeutic targets.