Abstract 180P
Background
Intrahepatic cholangiocarcinoma(iCCA) is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), and is also a highly malignant type of tumor. It is necessary to identify novel therapeutic targets.Histidine phosphatase LHPP were reported as a tumor suppressor for Hepatocellular Carcinoma and cervical cancer. And low level LHPP enhanced cell progression and tumor formation, and was associated with poor prognosis. So, we hypothesized that LHPP might be also related to the tumorigenesis of iCCA.
Methods
We analyzed the expression and clinical significance of LHPP in TCGA cohort and patient tissues. We transfected the iCCA cell lines with LHPP over-expression lentivirus or small interfering RNA. Cell proliferation were evaluated with the CCK-8 and colony formation assays. Cell apoptosis was evaluated by Annexin V/PI staining.Transwell assays were performed to assess cell invasion. Gene Set Enrichment Analysis (GSEA) was performed to enrich genes associated with LHPP. Markers of EMT and TGFβ/SMAD3 signaling pathway were evaluated by real-time PCR and western blotting.
Results
In this study, we found the mRNA and protein level of LHPP were downregulated in tumor tissues, and low level LHPP predicted a poor survival. LHPP overexpression suppressed RBE and HCCC-9810 cells growth and colony formation, and moderately promote cell apoptosis and EMT. In contrast, accumulated cell growth, colony formation, cell invasion and EMT were observed in LHPP knock down cells. We divided samples from the TCGA-CHOL cohort into two sub-group (LHPP_low and LHPP_High) by medina expression of LHPP, and found that TGFβ signaling pathway was significantly activated in LHPP_low group. The expression of TGFβ1 was negatively correlated with LHPP. We found that the expression of TGFβ1, TGFβ1R and p-SMAD3 were downregulated in LHPP overexpression cells, and these proteins were upregulated in LHPP down-expression cells.
Conclusions
We demonstrated that LHPP also serve as a suppressor gene to inhibit cell proliferation, cell invasion and EMT. And low level LHPP which was observed in tumor tissues predicted a poor survival. Mechanically, low level LHPP activate TGFβ/SMAD3 signaling pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fudan University Shanghai Cancer Center.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
164P - Multi-centered phase II trial of weekly 5-FU plus l-LV regimen as salvage line chemotherapy for oral fluorouracil resistant advanced gastric cancer (HGCSG1502)
Presenter: Yusuke Sasaki
Session: Poster display session
Resources:
Abstract
165P - Lenvatinib treatment for advanced hepatocellular carcinoma: The relationship between efficacy and safety
Presenter: Takayoshi Oikawa
Session: Poster display session
Resources:
Abstract
166P - The comparison between UGT1A1 single heterozygous and wild type regarding the clinical outcomes of fixed dose irinotecan monotherapy for advanced gastric cancer: Multicenter retrospective study
Presenter: Takahide Sasaki
Session: Poster display session
Resources:
Abstract
167P - Prognostic impact of the C-reactive protein/albumin ratio in advanced pancreatic cancer treated with GEM plus nab-PTX or FOLFIRINOX: Based on the results of a multicenter retrospective study (the NAPOLEON study)
Presenter: Akitaka Makiyama
Session: Poster display session
Resources:
Abstract
168P - A retrospective multicenter study evaluating the efficacy and safety of irinotecan in patients with advanced gastric cancer: Analysis of Glasgow Prognostic Score (GPS)
Presenter: Takuya Honda
Session: Poster display session
Resources:
Abstract
169P - M-phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl-2 and EMT-related signalling pathways
Presenter: Yizhuo Wang
Session: Poster display session
Resources:
Abstract
170P - Surgery alone versus surgery combined with Chemotherapy: Survival patterns among patients with fibrolamellar hepatocellular carcinoma
Presenter: Yasmine Ashraf
Session: Poster display session
Resources:
Abstract
171P - The clinical value of prognostic nutritional index in patients with anastomotic leakage after minimally invasive esophagectomy
Presenter: Yan Wang
Session: Poster display session
Resources:
Abstract
172P - Preoperative neutrophil‐to‐lymphocyte ratio (NLR) predicts recurrence after surgery in patient with pancreatic neuroendocrine neoplasm (PanNEN)
Presenter: Takayuki Miura
Session: Poster display session
Resources:
Abstract
173P - Cancer stem-like phenotypes including immune surveillance and its responsible genes in induced liver cancer stem-like cells
Presenter: Ryouichi Tsunedomi
Session: Poster display session
Resources:
Abstract