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Objective. To construct a nomogram-based prediction model for the clinical prognosis of patients with stage II and III colon cancer who underwent Xelox chemotherapy after laparoscopic radical resection based on large data sets. Methods. A total of 7,832 patients with colorectal cancer who received postoperative Xelox-based chemotherapy were screened from the Surveillance, Epidemiology, and End Results database (USA) as the training data set. In addition, 348 domestic patients were screened as the validation data set. Multivariate Cox regression analysis was performed to identify variables for inclusion in the nomogram-based prediction model. The predictive accuracy of the model was assessed using C-index and calibration curve. Results. Age, cell differentiation, nerve invasion, T and N stages of tumours, number of dissected lymph nodes, and carcinoembryonic antigen (CEA) level were found to influence the efficacy of postoperative chemotherapy. The nomogram-based prediction model was successfully constructed. The C-index of both the training set and validation set were higher than those of the 7th edition of TNM staging system published by the American Joint Commission on Cancer ( C − index of training data set = 0.728 , C − index of validation data set = 0.734 ). The prediction results of the model in the calibration curve showed a good fit with the actual situation. Conclusion. We successfully constructed a nomogram-based model to predict the clinical prognosis of patients with colorectal cancer receiving postoperative Xelox-based chemotherapy after laparoscopic radical resection, which showed good clinical application value for predicting the efficacy of postoperative Xelox-based chemotherapy in patients with colorectal cancer.

Background In gastric cancer (GC), circular RNAs (circRNAs) mainly play an important role in miRNA sponge, which not only indicate long‐term survival and prognosis but also increase resistance to the apoptosis. The purpose of the study is to explore new circRNAs and their underlying mechanisms in GC. Method Through rigorous retrieval strategies, we used the sva package to analyze and identify differentially expressed circRNAs (DECs) from three Gene Expression Omnibus microarray datasets (GSE83521, GSE89143, and GSE78092). Online website CSCD and CircInteractome were used to reveal the binding sites between miRNAs and DECs. The possible target miRNAs of the DECs identified based on miRNAs, and Cytoscape was used to create a regulatory network of circRNA‐miRNA‐mRNA and identified the hub genes which were further validated using The Cancer Genome Atlas database and Human Protein Atlas. Results Twenty‐eight DECs were obtained using the sva package. A regulatory network of circRNA‐miRNA‐mRNA (competing endogenous RNA) containing 15 circRNAs, 24 miRNAs, and 158 genes was identified. A protein‐protein interaction network based on the 158 genes was established, and further determined that 10 hub genes (SKA1, ANLN, CHEK1, SKA3, TOP2A, BIRC5, RRM2, NCAPG2, FANCI, and RAD51) were associated with some cancer‐related pathways based on the functional enrichment analysis. Finally, six hub genes (BIRC5, TOP2A, FANCI, NCAPG2, RAD51, and RRM2) were proven to influence the overall survival of GC. Conclusion Our study established a circRNA‐miRNA‐mRNA regulatory network and defined six circRNA‐related hub genes in GC, which could serve as potential therapeutic targets or prognostic biomarker for GC treatment., Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment annotations of differentially expressed genes (DEGs) (up‐(A) and down (B)‐regulated DEGs).

The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects. In addition, knockdown of TROP2 increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E-cadherin expression during epithelial-mesenchymal transition (EMT). Moreover, gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt phosphorylation, increased PTEN expression and postponed EMT of gallbladder cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of gallbladder cancer.

This article has been corrected: Due to errors in image processing, Figure 2C contains an image from the wrong cell line (GBC-SD cells). The corrected Figure 2C is shown below. The authors declare that these corrections do not change the results or conclusions of this paper.

B-cell CLL/lymphoma 9 protein (BCL-9), a multi-functional co-factor in Wnt signaling, induced carcinogenesis as well as promoting tumor progression, metastasis and chemo-resistance in colorectal cancer (CRC). However, the mechanisms for increased BCL-9 expression in CRC were not well understood. Here, we report that hypoxia, a hallmark of solid tumors, induced BCL-9 mRNA expression in human CRC cells. Analysis of BCL-9 promoter revealed two functional hypoxia-responsive elements (HRE-B and HRE-C) that can be specifically bound with and be transactivated by hypoxia inducible factors (HIF) -1α but not HIF-2α. Consistently, ectopic expression of HIF-1α but not HIF-2α transcriptionally induced BCL-9 expression levels in cells. Knockdown of endogenous HIF-1α but not HIF-2α by siRNA largely abolished the induction of HIF by hypoxia. Furthermore, there was a strong association of HIF-1α expression with BCL-9 expression in human CRC specimens. In summary, results from this study demonstrated that hypoxia induced BCL-9 expression in human CRC cells mainly through HIF-1α, which could be an important underlying mechanism for increased BCL-9 expression in CRC.

e23028Background: Circulating tumor DNA (ctDNA) holds great potential as a biomarker for cancer management. Unfortunately, with a half-life of < 2hrs, ctDNA is present in miniscule quantities and c...