Kinesin Family Member B18 Is Related to Gastric Mucin Phenotype and Contributes to Gastric Cancer Progression by Regulating Epithelial-Mesenchymal Transition

Abstract

Introduction: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC. Methods: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 gastric cancer cases. We also performed functional analysis using GC-derived cell lines. Result: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin-phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (P < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells. Discussion/Conclusion: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.

Colonic invasive adenocarcinoma with squamoid morules: A case report

“…Future studies are needed to identify and elucidate the pathogenesis of the pathway enhancement that occurs in squamoid morules and adenosquamous carcinoma through comprehensive expression analysis of the squamous cell carcinoma component because RNA sequencing from formalin-fixed paraffin-embedded samples has become possible. 9 In conclusion, we encountered a rare colorectal adenocarcinoma with a squamoid morule, which resembles the squamous cell carcinoma component and suggests that the diagnosis of adenosquamous carcinoma should not be made immediately.…”

“…Future studies are needed to identify and elucidate the pathogenesis of the pathway enhancement that occurs in squamoid morules and adenosquamous carcinoma through comprehensive expression analysis of the squamous cell carcinoma component because RNA sequencing from formalin‐fixed paraffin‐embedded samples has become possible. 9 …”

Discovering cancer stem-like cells using Spatial transcriptomic analysis: Nuclear factor I X as a novel therapeutic target for gastric cancer

“…We then obtained the genetic FC and ranked the gene list according to log2FC. We used the clusterProfiler R package to complete the gene set enrichment analysis, and the results were visualized using the ggplot2 R package, as described in our previous report (7). Canonical pathways were used as background gene sets for the pathway enrichment analysis.…”

“…In this study, 127 primary GC samples were collected from patients who underwent curative resection between 2012 and 2015 at Kure Medical Center and Chugoku Cancer Center (Kure, Hiroshima, Japan), as previously described (7). Archived FFPE tumor tissues obtained from resected specimens were used for immunohistochemical analyses.…”