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

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Eirini Martinou ◽  
Carla Moller-Levet ◽  
Angeliki Angelidi ◽  
Izhar Bagwan ◽  
Nariman Karanjia

Abstract 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 < 0.001) whereas HOXB9 inhibition markedly supressed CRC cell growth (p < 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.

Tumor Biology ◽  
2018 ◽  
Vol 40 (1) ◽  
pp. 101042831775294 ◽  
Author(s):  
Reetta Peltonen ◽  
Pia Österlund ◽  
Marko Lempinen ◽  
Arno Nordin ◽  
Ulf-Håkan Stenman ◽  
...  

Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland. The samples were taken before and 3 months after curative resection. Increased concentrations of CEA (>5 µg/L) and hCGβ (>1 pmol/L) 3 months after liver resection correlated with recurrence and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired overall survival, but postoperative TATI was not prognostic. Preoperatively elevated CEA and CA19-9 correlated with impaired overall survival, but not with recurrence. Neither preoperative hCGβ nor TATI was prognostic. In conclusion, CEA is a useful prognostic marker, when measured 3 months after resection of colorectal liver metastases. CA19-9 also has prognostic significance and may have additional value.


2019 ◽  
Vol 98 (10) ◽  

Introduction: Radical liver resection is the only method for the treatment of patients with colorectal liver metastases (CLM); however, only 20–30% of patients with CLMs can be radically treated. Radiofrequency ablation (RFA) is one of the possible methods of palliative treatment in such patients. Methods: RFA was performed in 381 patients with CLMs between 01 Jan 2001 and 31 Dec 2018. The mean age of the patients was 65.2±8.7 years. The male to female ratio was 2:1. Open laparotomy was done in 238 (62.5%) patients and the CT-navigated transcutaneous approach was used in 143 (37.5%) patients. CLMs <5 cm (usually <3 cm) in diameter were the indication for RFA. We used RFA as the only method in 334 (87.6%) patients; RFA in combination with resection was used in 36 (9.4%), and with multi-stage resection in 11 (3%) patients. We performed RFA in a solitary CLM in 170 (44.6%) patients, and in 2−5 CLMs in 211 (55.6%) patients. We performed computed tomography in each patient 48 hours after procedure. Results: The 30-day postoperative mortality was zero. Complications were present in 4.8% of transcutaneous and in 14.2% of open procedures, respectively, in the 30-day postoperative period. One-, 3-, 5- and 10-year overall survival rates were 94.8, 66.8, 43.9 and 16.6%, respectively, in patients undergoing RFA, and 90.6, 69.1, 52.8 and 39.2%, respectively, in patients with liver resections. Disease free survival was 63.2, 30.1, 18.4 and 13.1%, respectively, in the same patients after RFA, and 71.1, 33.3, 22.8 and 15.5%, respectively, after liver resections. Conclusion: RFA is a palliative thermal ablation method, which is one of therapeutic options in patients with radically non-resectable CLMs. RFA is useful especially in a non-resectable, or resectable (but for the price of large liver resection) solitary CLM <3 cm in diameter and in CLM relapses. RFA is also part of multi-stage liver procedures.


2017 ◽  
Vol 42 (4) ◽  
pp. 1180-1191 ◽  
Author(s):  
Atsushi Kobayashi ◽  
Toshimi Kaido ◽  
Yuhei Hamaguchi ◽  
Shinya Okumura ◽  
Hisaya Shirai ◽  
...  

2009 ◽  
Vol 24 (11) ◽  
pp. 1349-1349
Author(s):  
Georgios C. Sotiropoulos ◽  
Evangelos Tagkalos ◽  
Andreas Kreft ◽  
Vasiliy Moskalenko ◽  
Ursula Gönner ◽  
...  

2016 ◽  
Vol 27 ◽  
pp. ii49
Author(s):  
M. Marques ◽  
H.S. de Castro Ribeiro ◽  
W.L. Costa ◽  
A.L. Diniz ◽  
A. Godoy ◽  
...  

2020 ◽  
Vol 9 (12) ◽  
pp. 4027
Author(s):  
Sebastian Knitter ◽  
Andreas Andreou ◽  
Daniel Kradolfer ◽  
Anika Sophie Beierle ◽  
Sina Pesthy ◽  
...  

Minimal-invasive hepatectomy (MIH) has been increasingly performed for benign and malignant liver lesions with most promising short-term results. However, the oncological role of MIH in the treatment of patients with colorectal liver metastases (CRLM) needs further investigation. Clinicopathological data of patients who underwent liver resection for CRLM between 2012 and 2017 at the Department of Surgery, Charité-Universitätsmedizin Berlin, and the Inselspital Bern were assessed. Postoperative outcomes und long-term survivals of patients following MIH were compared with those after conventional open hepatectomy (OH) after 1:1 propensity score matching. During the study period, 229 and 91 patients underwent liver resection for CRLM at the Charité Berlin and the Inselspital Bern, respectively. Patients who underwent MIH in one of the two centers (n = 69) were compared with a matched cohort of patients who underwent OH. MIH was associated with lower complication rates (23% vs. 44%, p = 0.011), shorter length of intensive care unit stay (ICU, 1 vs. 2 days, p = 0.043), shorter length of hospital stay (7 vs. 11 days, p < 0.0001), and a reduced need for intraoperative transfusions (12% vs. 25%, p = 0.047) compared to OH. R0 status was achieved in 93% and 75% of patients after MIH and OH, respectively (p = 0.005). After a median follow-up of 31 months, MIH resulted in similar five-year overall survival (OS) rate (56% vs. 48%, p = 0.116) in comparison to OH. MIH for CRLM is associated with lower postoperative morbidity, shorter length of ICU and hospital stay, reduced need for transfusions, and comparable oncologic outcomes compared to the established OH. Our findings suggest that MIH should be considered as the preferred method for the treatment of curatively resectable CRLM.


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