Search

BACKGROUND: Gastrointestinal malignant cancers affect many sites in the intestinal tract, including the colon. In this study, we purposed to improve prognostic predictions for colon cancer (CC) patients by establishing a novel biosignature of immune-related genes (IRGs) based on the tumor microenvironment (TME). METHODS: Using the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, we calculated the stromal and immune scores of every CC patient extracted from The Cancer Genome Atlas (TCGA). We then identified 4 immune-related messenger RNA (mRNA) biosignatures through a Cox and least absolute shrinkage and selection operator (LASSO) univariate analysis, and a Cox multivariate analysis. Relationships between tumor immune infiltration and the risk score were evaluated through the CIBERSORT algorithm and Tumor Immune Estimation Resource (TIMER) database. RESULTS: Our studies showed that individuals who had a high immune score (P=0.017) and low stromal score (P=0.041) had a favorable overall survival (OS) rate. By comparing high/low scores cohort, 220 differentially expressed genes (DEGs) were determined. Then an immune-related four-mRNA biosignature, including PDIA2, NAFTC1, VEGFC, and CD1B was identified. Kaplan-Meier, calibration, and receiver operating characteristic (ROC) curves verified the model’s performance. By using univariate and multivariate Cox analyses, we found each biosignature was an independent risk factor for assessing a CC patient’s survival. Three external GEO cohorts validated its good efficiency in estimating OS among individuals with CC. Moreover, the signature was also related to infiltration of several cells of the immune system in the tumor microenvironment. CONCLUSIONS: The resultant model in our study included 4 IRGs associated with the TME. These IRGs can be utilized as an auxiliary variable to estimate and help improve the prognosis of individuals with CC.

Background Pancreatic cancer is an aggressive cancer and is predicted to become the second leading cause of cancer-related deaths in China. To understand the epidemic trend of pancreatic cancer and formulate targeted preventive measures, it is important to analyze the incidence and mortality of pancreatic cancer. Methods The incidence and mortality data of pancreatic cancer in China were obtained from Global Burden of Disease (GBD) data. We used joinpoint regression analysis to calculate the magnitude and direction of trends, and the age-period-cohort method to analyze the effects of chronological age, time period, and birth cohort. Results The age-standardized rates (ASRs) for both incidence and mortality of pancreatic cancer increased from 1990 to 2019, and were higher in males than females. The incidence and mortality rates have increased year by year in the age group above 25 years. The most common age group was 55–79 years, accounting for approximately 50% of all incident cases. In terms of incidence and mortality rates, the overall net drifts were above 0. The local drifts in all age groups were above 0 in both sexes and males, while the local drifts in the 15–39 age groups were below 0 in females. The longitudinal age curves increased with age, with higher incidence and mortality rates, mainly in older age groups. The period rate ratios increased by year. The cohort rate ratios showed an upward trend before 1970 and fluctuated after 1975. Conclusions The burden of pancreatic cancer is still very high in China, and attention should be paid to the key population that is, males and older people. The results of our study can be used by policy makers to allocate resources efficiently to improve early diagnosis and treatment, improving the awareness of self-protection, and advocating a healthy lifestyle to prevent pancreatic cancer.

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Background Hepatitis C virus (HCV) infection is a main contribution to the increase in hepatocellular carcinoma (HCC) incidence and patients’ death recently, but prognostic biomarkers for HCV-related HCC remain rarely reported. This study was to identify an lncRNA prognostic signature for HCV-HCC patients and explore their underlying function mechanisms. Methods In total, 102 HCV-HCC samples and 50 normal control samples were obtained from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to screen an lncRNA signature that could predict overall survival (OS) and then, the risk score was calculated using this signature. The prognostic potential of this risk score was evaluated by drawing Kaplan-Meier, receiver operating characteristic (ROC) curves and performing multivariate Cox regression analyses with clinical variables. Furthermore, a co-expression and competing endogenous RNA (ceRNA) networks were constructed to explore the functional mechanisms of lncRNAs. Results Multivariate Cox regression showed six lncRNAs (SLC16A1-AS1, ZFPM2-AS1, JARID2-AS1, LINC01426, USP3-AS1 and LYPLAL1-AS1) were significantly associated with OS of HCV-HCC patients. These six lncRNAs were used to establish a risk score model, which displayed a higher prognosis prediction accuracy [area under the ROC curve (AUC) = 0.95 for training set; AUC = 0.885 for testing; AUC = 0.907 for entire set]. Also, this was independent of various clinical variables. The crucial co-expression (LINC01426/SLC16A1-AS1-AURKA/SFN/CCNB1, ZFPM2-AS1/LYPLAL1-AS1/JARID2-AS1-TSSK6) or ceRNA (USP3-AS1-hsa-miR-383-SFN) interaction axes were identified. Conclusion Our study identified a novel six-lncRNA prognosis signature for HCV-HCC patients and indicated their underlying mechanisms for HCC progression.

Aim: In this study, we aim to use bioinformatics approach to identify paclitaxel-targeted modulators potentially involved in the process of reversing the trastuzumab resistance. Materials & methods: We extracted data from GSE77346 to identify potential trastuzumab resistance-related genes, used bioinformatics analysis and functional/activity network approach to find genes involved in trastuzumab resistance reversal. Results: We identified hub differentially expressed genes related to trastuzumab resistance, trastuzumab targeting and paclitaxel targeting, respectively. We then found C-Jun may be critical in trastuzumab resistance reversal. This process may involve transcriptional activation of DUSP1 by JUN, which lead to regulation of DUSP1-related signaling pathways. Conclusion: The present study revealed paclitaxel may reverse the trastuzumab resistance by JUN, which possibly in turn regulated DUSP1 and DUSP1-related signaling pathways.

e18072 Background: Breast cancer is ranked as the most common cancer among women in China, cases in China account for about 300,000 of all newly diagnosed breast cancers each year. Developing Clinical Decision Supporting System (CDSS) to assist early diagnosis breast cancer is valuable, however, lack of semantic interoperability in CDSS has been identified as the main obstacle for broad adoption of CDSS. Ontology is considered to be one of the effective approaches to bridge the terminology gap between various clinical systems and data sources. In this study, we describe our efforts in transforming breast cancer clinical knowledge into computable ontology to support breast cancer early diagnosis. Methods: We have built a breast cancer ontology (BCO) to support our CDSS pipeline. A number of NCCN clinical practice guidelines in Oncology for Breast Cancer and the breast cancer diagnosis and treatment guidelines of China are the main knowledge sources of the BCO. BCO is a manually curated resource that contains concepts and relations of breast cancer clinical findings, demographics, laboratory tests, imaging results, treatments, pathologies, cancer stages, body structure and follow-up information. These curated knowledges are annotated through interoperable standard vocabulary SNOMED CT. Two physicians reviewed and evaluated the BCO. Results: Concepts in BCO currently contains 79 clinical findings, 8 demographics, 42 laboratory tests, 105 imaging results, 332 treatments, 141 pathology and cancer stages, 30 body structures and 3 follow-ups. Relations are defined such as finding site, associated with, etc. The concepts hierarchies and relationships were built by using Protégé to support OWL representation. As an initial evaluation results, most of concepts could be mapped to SNOMED CT, but there are some concepts could not be exactly mapped to SNOMED CT. We created local Chinese Vocabularies for these local terms. Conclusions: Based on interoperable BCO, a group of computable rules are developed by adding statements according to early diagnosis criteria of breast cancer. Diagnosis assistance around complex patients is supported though connecting the Electronic Health Record (EHR). This is an ongoing development that the BCO is continuingly enriched with standard concepts, relations and integrate with individual instances to support broader adoptability.

Little is known about the relationship about Helicobacter pylori (H. pylori) infection and pancreatic, and this study was set to investigate how H. pylori infection is correlated with pancreatic cancer and provide references for the clinical prevention and treatment of pancreatic cancer. 56 cases of pancreatic cancer patients admitted to the hospital from August 2012 to August 2013 were collected as the observation group. The anti-Hp IgG (H. pylori-specific antibodies), Hp IgM (H. pylori antibodies), and CagA-Hp-IgG (H. pylori serotoxin-associated protein a antibody) in the serum were measured and compared with the related indicators of control group (60 cases of healthy subjects). The H. pylori infection rate was 64.29 % in the observation group, and that in the control group was 46.67 %. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P < 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53 % in the control group, for which the observation group was significantly higher than the control group (P < 0.05). The occurrence of H. pylori infection in patients with pancreatic cancer was also positively correlated with the smoking history and the history of chronic pancreatitis (P < 0.05). Helicobacter pylori infection is one of the risk factors for pancreatic cancer, and the patients with positive CagA-Hp have the higher risk, so the prevention and treatment of H. pylori infection would be beneficial for the prevention and treatment of pancreatic cancer.