Pancreatic cancer is a lethal disease, and resistance to chemotherapy is a critical factor influencing the postoperative prognosis. Tumour heterogeneity is an important indicator of chemoresistance. Therefore, we analysed tumour heterogeneity in preoperative computed tomography scans by performing texture analysis using the grey-level run-length matrix and analysed the correlation of survival with the value obtained in these analyses. We analysed 116 consecutive patients who underwent curative resection and had preoperative contrast-enhanced computed tomography data available for analysis. A region of interest was drawn on all slices with a visible tumour and normal pancreas on the arterial phase computed tomography scans; the correlation of pathological characteristics with grey-level run-length matrix features was analysed. We then performed Kaplan–Meier survival curve analysis among pancreatic cancer patients. The grey-level non-uniformity values in grey-level run-length matrix features for tumours were higher than those for normal pancreas. High grey-level non-uniformity values represent a non-uniform texture, i.e., heterogeneity. Grey-level run-length matrix features showed that recurrence-free survival was shorter in the group with high grey-level non-uniformity 135 values (p = 0.025). Our analyses of the correlation between pathological outcomes and grey-level run-length matrix features in pancreatic cancer patients showed that grey-level non-uniformity values were powerful prognostic indicators.
Few studies have examined the risk factors for gallbladder (GB) disease in young adults. This study aimed to evaluate risk factors for GB disease in young adults based on big data in Korea. All participants underwent routine checkup at the Korea Medical Institute from June 2014 to May 2015. After excluding 677 individuals with missing information in records, 724,114 individuals (435,635 men, 288,479 women) were finally included. The definition of abnormal GB finding included stones, sludge, polyps, and adenomyomatosis detected using ultrasonography. All statistical analyses were performed using SAS software version 9.2. Overall, 27,130 (17.5%) individuals were diagnosed as having abnormal GB finding in the young age group (N = 154,463, aged 20–39 years). In men, significant differences in low-density lipoprotein (LDL) and cholesterol levels were observed between the abnormal GB finding group and normal GB group (p < 0.05). In women, a significant difference in smoking history was noted between the abnormal GB finding group and normal GB group (p < 0.05). The prevalence rate of GB stones was 1.9% (27,979/154,463) in the young age group. High body mass index (BMI), large thigh circumference, and low high-density lipoprotein (HDL) level in women and low HDL level in men were independent risk factors for the presence of GB stones (p < 0.05). In this study, obesity-related factors (BMI, waist size, thigh circumference, and cholesterol, LDL, and HDL levels) correlated with GB disease in the young generation of Korea.
Specific protein 1 (SP1) is associated with aggressive behavior, invasive clinical phenotype and poor clinical outcomes in various cancers. We studied whether SP1 exerts its effect on invasiveness and promotion of the epithelial-mesenchymal transition (EMT) by regulating lysyl oxidase-like 2 (LOXL2) in pancreatic ductal adenocarcinoma (PDAC) cell lines. We showed that silencing of SP1 in MIA Paca-2 cell significantly decreased cell invasion and migration. In MIA Paca-2 cells, silencing of SP1 induced a reduction of LOXL2 expression, whereas LOXL2 silencing did not lead to a decrease in the expression of SP1. Chromatin immunoprecipitation assay demonstrated the binding of SP1 to LOXL2 promoter. Wound healing and transmigration assays also showed that transfection of both SP1 and LOXL2 siRNA induced most significant decrease of cell invasion and migration compared to either SP1 or LOXL2-only silenced cells. Finally, we investigated the prognostic value of SP1 in patients with PDAC and SP1/LOX2 expression was examined by immunochemistry. Univariate and multivariate analyses showed that tumor differentiation and co-expression of SP1 and LOXL2 were independent factors for disease-free survival. In summary, our study demonstrates that SP1 modulates EMT and is involved in tumor invasion and migration of PDAC cells through the regulation of LOXL2.
The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values. Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67–1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis. The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor. Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors.
1 October 2013 in Infection, Genetics and Evolution