HTATIP2 Overexpression was Associated With a Good Prognosis in Gastric Cancer

• Published in: Technology in cancer research & treatment 2024-01, Vol.23, p.15330338231187254-15330338231187254
• Main Authors: Park, Sun Yi, Park, Ji-Ho, Yang, Jung Wook, Jung, Eun-Jung, Ju, Young-Tae, Jeong, Chi-Young, Kim, Ju-Yeon, Park, Taejin, Park, Miyeong, Lee, Young-Joon, Jeong, Sang-Ho
• Format: Article
• Language: English
• Subjects: Acetyltransferases - genetics; Acetyltransferases - metabolism; Adenocarcinoma - genetics; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Gene Expression Regulation, Neoplastic; Guanine Nucleotide Exchange Factors - genetics; Humans; Lymphatic Metastasis; Prognosis; Stomach Neoplasms - diagnosis; Stomach Neoplasms - pathology; Survival Analysis; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/15330338231187254

The purpose of this study was to compare the transcriptomes of poorly cohesive carcinoma (PCC; diffuse-type) and well-differentiated tubular adenocarcinoma (WD; intestinal-type) using gastric cancer (GC) tissues and cell lines and to evaluate the prognostic role of HIV-1 Tat Interactive Protein 2 (HTATIP2). We performed next-generation sequencing with 8 GC surgical samples (5 WD and 3 PCC) and 3 GC cell lines (1 WD: MKN74, and 2 PCC: KATOIII and SNU601). Immunohistochemistry was used to validate HTATIP2 expression. We performed functional analysis by HTATIP2 overexpression (OE). Kaplan-Meier survival plots and the PrognoScan database were used for survival analysis. The genes with significantly reduced expression in PCC versus WD (in both tissues and cell lines) were HTATIP2, ESRP1, GRHL2, ARHGEF16, CKAP2L, and ZNF724. According to immunohistochemical staining, the HTATIP2-OE group had significantly higher number of patients with early GC (EGC) (T1) (  = .024), less lymph node (LN) metastasis (  = .008), and low TNMA stage (  = .017) than HTATIP2 underexpression (UE) group. Better survival rates were confirmed in the HTATIP2 OE group by Kaplan-Meir survival and PrognoScan analysis. In vitro, HTATIP2-OE in KATO III cells caused a significant decrease in cancer cell migration and invasion. Decreased Snail and Slug expression in HTATIP2 OE cells suggested that epithelial-mesenchymal transition is involved in this process. HTATIP2 might be a good prognostic marker and a candidate target for GC treatment.