Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid‐interferon‐induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms of OLFM4 for regulating GRIM19‐STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions and regulations of OLFM4, GRIM19, and STAT3 activation in HCC progression were evaluated using surgical specimens collected from 111 HCC patients or 2 HCC cell lines
in vitro
. Moreover, the cancer stem cell–like property of OLFM4 mediated by leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5), known as an intestinal stem cell marker, was investigated. OLFM4 was increased in HCC compared with adjacent liver tissue. The multivariate analysis revealed that high OLFM4 expression was an independent factor for poor prognosis. OLFM4 expression was negatively correlated with GRIM19 expression and positively correlated with STAT3 activation in HCC, thereby increasing cell cycle progression. OLFM4 knockdown in HCC cells increased GRIM19 expression and inhibited STAT3 activation; however, after double knockdown of GRIM19 and OLFM4, STAT3 activation decreased by OLFM4 knockdown was increased again. OLFM4 knockdown increased cell apoptosis, inhibited cell proliferation, and suppressed cancer stem cell–like property in HCC cells. The incidence of hematogenous recurrence was higher in HCC patients with high OLFM4 expression, suggesting that anoikis resistance of HCC was enhanced by OLFM4. In clinical cases, LGR5 expression and CD133 expression was correlated with OLFM4 expression in HCC, leading to poor patient prognosis.
In vitro
, LGR5 enhanced cancer stem cell–like property by up‐regulating OLFM4 through the Wnt signaling pathway.
Conclusion
: OLFM4 is induced by the LGR5‐Wnt signaling pathway and is strongly associated with aggressive tumor progression and poor prognosis in HCC by regulating STAT3‐induced tumor cell proliferation and cancer stem cell–like property. Therefore, OLFM4 is a novel prognostic predictor and a potential therapeutic target for patients with HCC.
Chiba Rosai Hospital has one of the leading treatment records in Japan for cholecystitis (17 th ) , colectomy (37 th ) , and peritonitis/intra-abdominal abscess (73 rd ) in the 2019 National Clinical Database (NCD) . Moreover, more than 90% of the operations are performed using a laparoscope. Indeed, in the gastrointestinal surgery department, which has many experienced surgeons, it is desirable to improve irrigation techniques during laparoscopic surgery. However, the application of new methods may increase patient risks in the field of clinical medicine, and there are issues such as ethical regulations and infection risks regarding the collection of purulent substances to be removed. Therefore, as a preliminary step in conducting clinical trials, it is desirable to consider model tests to improve dirt removal ability and estimate safety.The most advanced modeling techniques in the cleaning field are probably related to the development of detergents. Model studies have established cleaning theories Abstract: To improve the outcome of laparoscopic gastrointestinal surgery, improvement in the technology for removing purulent substances from the abdominal cavity is required. Ultrasonic cleaning technology may be suitable for the task. However, it is necessary to examine cleaning efficiency and safety through model tests that can lead to clinical trials for practical use. Nine surgical specialists first estimated the distribution of the actual attachment of purulent substances using videos of removing pus-like model dirt as an evaluation scale. Subsequently, cleaning tests were conducted using a small-size shower with model dirt that was somewhat difficult to remove, and its suitability as a model sample was confirmed. A mixture of miso and other substances was attached to a silicon sheet to prepare a test sample. The model dirt could be removed within a few seconds by cleaning using a probe-type ultrasonic homogenizer while the test sample was submerged in water. This performance greatly surpassed that of water flow cleaning under increased water pressure. An ultrasonic cleaner that is useful for irrigation during laparoscopic surgery will be suitable for practical use in laparoscopic surgery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.