Pancreatic cancer (PC) is a highly lethal human cancer. We previously found that Serine protease 3 (PRSS3), as an oncogene, is significantly upregulated in PC. In this study, we aimed to investigate the potential mechanism of PRSS3 dysregulation in PC. In this research, low miR-217 and high circ-ADAM9 expression were found in PC tissues and cell lines, which was closely associated with advanced clinical stage and lymph node metastasis. Patients with low miR-217 or high circ-ADAM9 expression had shorter survival time than those with high miR-217 or low circ-ADAM9 expression. Functionally, manipulation of miR-217 and circ-ADAM9 expression showed opposite effects on cell proliferation, migration and invasion. Stepwise mechanism studies indicated that circ-ADAM9 alleviated the inhibitory effect of miR-217 on PRSS3 by directly sponging miR-217 to increase the expression level of PRSS3, resulting in the activation of ERK/VEGF signalling pathway. In vivo, circ-ADAM9 silencing or miR-217 overexpression evidently retarded the growth of tumour, and the combination of them exhibited an additive inhibitory effect on tumourigenicity. Briefly, the ceRNA regulatory network of circ-ADAM9/miR-217/PRSS3 plays a pivotal role in PC progression by the regulation of ERK/VEGF signalling pathway.

The aim of this study was to develop a noninvasive serological diagnostic approach in identifying and evaluating a panel of candidate autoantibodies to tumor‐associated antigens (TAAs) based on protein microarray technology for early detection of ovarian cancer (OC). Protein microarray based on 154 proteins encoded by 138 cancer driver genes was used to screen candidate anti‐TAA autoantibodies in a discovery cohort containing 17 OC and 27 normal controls (NC). Indirect enzyme‐linked immunosorbent assay (ELISA) was used to detect the content of candidate anti‐TAA autoantibodies in sera from 140 subjects in the training cohort. Differential anti‐TAA autoantibodies were further validated in the validation cohort with 328 subjects. Subsequently, 112 sera from the patients with ovarian benign diseases with 104 OC sera and 104 NC sera together were recruited to identify the specificity of representative autoantibodies to OC among ovarian diseases. Five TAAs (GNAS, NPM1, FUBP1, p53, and KRAS) were screened out in the discovery phase, in which four of them presented higher levels in OC than controls (P < .05) in the training cohort, which was consistent with the result in the subsequent validation cohort. An optimized panel of three anti‐TAA (GNAS, p53, and NPM1) autoantibodies was identified to have relatively high sensitivity (51.2%), specificity (86.0%), and accuracy (68.6%), respectively. This panel can identify 51% of OC patients with CA125 negative. This study supports our assumption that anti‐TAA autoantibodies can be considered as potential diagnostic biomarkers for detection of OC; especially a panel of three anti‐TAA autoantibodies could be a good tool in immunodiagnosis of OC.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. In this article, we show that expression of abnormal spindle‐like microcephaly‐associated protein (ASPM) is up‐regulated in liver cancer samples, and this up‐regulation is significantly associated with tumor aggressiveness and reduced survival times of patients. Down‐regulation of ASPM expression inhibits the proliferation, invasion, migration and epithelial‐to‐mesenchymal transition of HCC cells in vitro and inhibits tumor formation in nude mice. ASPM interacts with disheveled‐2 (Dvl2) and antagonizes autophagy‐mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule‐associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β‐catenin signaling activation in HCC cells. Thus, our results define ASPM as a novel oncoprotein in HCC and indicate that disruption of the Wnt–ASPM–Dvl2–β‐catenin signaling axis might have potential clinical value.

Substantial evidence manifests the occurrence of autoantibodies to tumor-associated antigens (TAAs) in the early stage of hepatocellular carcinoma (HCC), and previous studies have mainly focused on known TAAs. In the present study, protein microarrays based on cancer driver genes were customized to screen TAAs. Subsequently, autoantibodies against selected TAAs in sera were tested by enzyme-linked immunosorbent assays (ELISA) in 1175 subjects of three independent datasets (verification dataset, training dataset, and validation dataset). The verification dataset was used to verify the results from the microarrays. A logistic regression model was constructed within the training dataset; seven TAAs were included in the model and yielded an area under the receiver operating characteristic curve (AUC) of 0.831. The validation dataset further evaluated the model, exhibiting an AUC of 0.789. Remarkably, as the aggravation of HCC increased, the prediction probability (PP) of the model tended to decrease, the trend of which was contrary to alpha-fetoprotein (AFP). For AFP-negative HCC patients, the positive rate of this model reached 67.3% in the training dataset and 50.9% in the validation dataset. Screening TAAs with protein microarrays based on cancer driver genes is the latest, fast, and effective method for finding indicators of HCC. The identified anti-TAA autoantibodies can be potential biomarkers in the early detection of HCC.

Background: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021). Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI). Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors. Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.

Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen‐antibody system) were taken as candidate tumor‐associated antigens (TAAs). Enzyme‐linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model. Eleven TAAs were selected (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2). The titer of six autoantibodies (PCNA, AAGAB, CDC37L1, TAF7L, DUSP6, and ZIC2) had a significant difference in any of the pairwise comparisons among the HCC, liver cirrhosis, and normal control groups. The titer of these autoantibodies had an increasing tendency. Finally, an optimum diagnostic model was constructed with the six autoantibodies. The AUCs were 0.826 in the train set and 0.773 in the test set. The area under the curve (AUC) of this panel for diagnosing early HCC was 0.889. The diagnostic ability of the panel reduced with the progress of HCC. The positive rate of the panel in diagnosing alpha‐fetoprotein (AFP)‐negative patients was 75.6%. For early HCC, the sensitivity of the combination of AFP with the panel was 90.9% and superior to 53.2% of AFP alone. The novel immunodiagnosis panel combining AFP may be a new approach for the diagnosis of HCC, especially for early‐HCC cases.