Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K) and phosphorylated Akt (pAkt) proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial–mesenchymal transition (EMT) revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In conclusion, our findings imply that PGRN modulates cell proliferation by dysregulating the G1 phase, inhibiting apoptosis, and that it plays a role in the EMT affecting CCA cell motility, possibly via the PI3K/pAkt pathway.

Background: Patients with cholangiocarcinoma (CCA) usually have no specific symptoms until an advance stage of the disease and curative treatment is not possible. Patients with early stage, operable disease can be found using ultrasonography (US). A US-screening program was implemented in Thailand where CCA incidence is the highest worldwide. Here we evaluate the effectiveness of the program by comparing the proportion of individuals with early stage CCA in the screening group with that of the walk-in group presenting at hospitals with clinical symptoms.Methods: All patients had a pathological diagnosis of CCA. The difference in the proportions and the 95% confidence interval (CI) were obtained using binomial regression.Results: Of the 762 histologically proven CCA cases, 161 were from the screening group and 601 from the walk-in group. The proportion of early stage CCA (stages 0 to II) diagnosed was 84.5% in the screening and 21.6% in the walk-in groups. After adjustment age, gender, and liver fluke infection, there was a significantly higher proportion (P < 0.001) and higher chance (P < 0.001) of having early stage CCA in the screening group than in the walk-in group.Conclusions: US-screening is an effective tool for detecting early stage, operable CCA in high incidence areas.

Background: Serum antibody for Opisthorchis viverrini (OV) is strong evidence for a history of OV infection in people. Currently, no studies have examined whether varying cholangiocarcinoma (CCA) prevalence levels are linked to previous OV infection nor have they provided comprehensive assessment and characterization of OV-associated CCA. Objective: Our study examined the prevalence of serum IgG antibodies for OV-positive CCA cases and determined whether there were correlations of IgG antibodies with histopathologic features, HER2, PD-L1, and FGFR2 expression, as well as their roles on the patients' survival. Methods: The study involved 221 CCA surgical patients at

Distal cholangiocarcinoma (dCCA) is a rare type of CCA in Asia, even in Opisthorchis viverrini-prevalent Northeastern Thailand. The clinical ambiguity and imprecision of diagnosis surrounding this malignancy result in high mortality due often to advanced/metastatic disease on presentation. We aim to identify a prognostic factor that can improve the performance stratification and influence the outcome of dCCA patients after curative resection. A total of 79 patients who underwent curative-intended surgery for dCCA was enrolled. Possible risk factors for survival were analyzed with log-rank test, and independent factors with Cox regression model. dCCA patients were staged and classified according to the 8th edition the American Joint Committee on Cancer (AJCC) Staging Manual. Results were then compared with the revised classification employing the prognostic factor identified from multivariate analysis. Multivariate analysis revealed that growth pattern (p &lt; 0.01) and distant metastasis (p = 0.012) were independent factors. Growth patterns comprise intraductal (ID), periductal infiltrating (PI), mass-forming (MF), and mixed types. When dCCA patients were grouped into those having good and poor outcomes (with and without ID components, respectively). The survival outcomes significantly differed among patients with and without ID components, which was better than with the 8th AJCC staging system in our cohort. Furthermore, Chi-square test showed that patterns without ID components (PI, MF, PI + MF) correlated with lymph node and distant metastasis. Therefore, classification of dCCA patients after curative-intended surgical resection based on growth pattern provides additional beneficial information for the prediction of survival in dCCA patients.

Background Previous studies have shown the association between Campylobacter species infection and that environmental factors, poor oral hygiene in particular, are linked to an increased risk of esophageal cancer (EC). However, no study has reported on these factors in Thailand. Thus, this study’s objective was to evaluate the impact of the relationship between Campylobacter infection and environmental factors on EC incidence in the population of Thailand. Methods Data from a case–control study were collected from 105 newly diagnosed EC cases and 105 controls recruited from 2007 to 2017. Infection with Campylobacter spp. was detected in the formalin-fixed paraffin-embedded (FFPE) tissue of EC taken from gastroesophageal biopsy specimens obtained from the participants, and evaluated using TaqMan® real-time PCR. Multivariable logistic regression was performed to calculate the odds ratios (ORs) and perform data analysis. Results Smoking, alcohol use, a family history of cancer, history of gastroesophageal reflux disease, poor oral hygiene and Campylobacter spp. infection were shown to be significant risk factors for EC (p  <  0.05). The combination of poor oral hygiene and infection with Campylobacter spp. constituted significant risk for EC (p  <  0.001). In addition, the risk of EC in subjects co-infected with C. rectus and C. concisus that practiced poor oral hygiene was even higher and was significant (ORadj  =  4.7; 95% CI 2.41–9.98; p  =  0.003). Conclusions In Thailand, the major risk factors for EC are smoking status, alcohol drinking, family history of cancer, GERD, poor oral hygiene and Campylobacter spp. infection. This study found Campylobacter spp. prevalence to be associated with EC and appears to be enhanced by poor oral hygiene, suggesting that a combination of poor oral hygiene and Campylobacter species infection may together act as an important etiological risk factor for EC.