English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Aims Homeobox (HOX) proteins are emerging as promising biomarkers and targets for gene-therapy in cancer; however, their role in colorectal liver metastases (CRLM) is unknown. This study aims to investigate the role of HOXB9 as prognostic marker and potential therapeutic target in CRLM. Methods Two patient-cohorts were included: a) Patients with colorectal cancer (CRC) from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database (n = 614) and b) Institutional patient cohort who underwent liver resection for CRLM (n = 110) between 2007-2014. Primary outcome was 10-year overall survival (OS). COX regression and Kaplan-Meier survival analyses were performed including HOXB9 expression, demographics, clinicopathological and treatment-related variables. HOXB9 gene expression was modulated to assess its impact on CRC cell growth in vitro. Therefore, we conducted experimental studies using plasmid-vector and siRNA-interference to overexpress and knockdown HOXB9 respectively. Results Univariable TCGA analysis showed that HOXB9 did not predispose to poor OS (HR = 1, 95%CI:0.92-1.1, p = 0.620). On the contrary, univariable analysis in the CRLM patient cohort showed that high HOXB9 levels, right sided CRC, CRLM number≥4, CRLM diameter≥5cm, and intrahepatic recurrence were associated with significantly increased risk for worse OS. On multivariable models, only high HOXB9 expression (HR = 3.82, 95%CI:1.59-9.2, p = 0.003) and intrahepatic recurrence (HR = 4.28, 95%CI:1.88-9.72, p = 0.001) retained significance as independent prognostic factors after liver resection. Experimental studies showed that HOXB9 overexpression increased cell proliferation (p &amp;lt; 0.001) whereas HOXB9 inhibition markedly supressed CRC cell growth (p &amp;lt; 0.001) in vitro. Conclusions HOXB9 demonstrates oncogenic properties and may serve as novel prognostic marker and potential target for gene-directed therapy in CRC/CRLM.

Moy.01HOXB9: an emerging novel prognostic marker and potential target for gene-therapy in colorectal liver metastases