Early diagnosis of colon cancer (CC) is clinically important, as it can significantly improve patients' survival rate and quality of life. Although the potential role for small extracellular vesicles (sEVs) in early detection of many diseases has been repeatedly mentioned, systematic screening of plasma sEVs derived early CC specific biomarkers has not yet been reported. In this work, plasma sEVs enriched fractions were derived from 15 early‐stage (TisN0M0) CC patients and 10 normal controls (NC). RNA sequencing identified a total number of 95 sEVs enriched fraction derived miRNAs with differential expression between CC and NC, most of which (60/95) was in well accordance with tissue results in the Cancer Genome Atlas (TCGA) dataset. Among those miRNAs, we selected let‐7b‐3p, miR‐139‐3p, miR‐145‐3p, and miR‐150‐3p for further validation in an independent cohort consisting of 134 participants (58 CC and 76 NC). In the validation cohort, the AUC of 4 individual miRNAs ranged from 0.680 to 0.792. A logistic model combining two miRNAs (i.e. let‐7b‐3p and miR‐145‐3p) achieved an AUC of 0.901. Adding the 3rd miRNA into this model can further increase the AUC to 0.927. Side by side comparison revealed that sEVs miRNA profile outperformed cell‐free plasma miRNA in the diagnosis of early CC. In conclusion, we suggested that circulating sEVs enriched fractions have a distinct miRNA profile in CC patients, and sEVs derived miRNA could be used as a promising biomarker to detect CC at an early stage.

Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cells, cytokines, extracellular vesicles, and extracellular matrix. All the stromal components together with the tumor cells form the tumor microenvironment (TME). In addition, extracellular physical and chemical factors, including extracellular pH, hypoxia, elevated interstitial fluid pressure, and fibrosis, are closely associated with tumor progression, metastasis, immunosuppression, and drug resistance. Cellular and extracellular components in TME contribute to nearly all procedures of carcinogenesis. By summarizing the recent work in this field, we make a comprehensive review on the role of cellular and extracellular components in the process of carcinogenesis and their potential application in early diagnosis of cancer. We hope that a systematic review of the diverse aspects of TME will help both research scientists and clinicians in this field.

Helicobacter pylori has coexisted with humans for approximately 60,000 years and greater than 50% of the global population is infected with H. pylori. H. pylori was successfully cultured in vitro in 1983 and studies of H. pylori have achieved substantial advances over the last 35 years. Since then, H. pylori has been characterized as the primary pathogenic factor for chronic gastritis, peptic ulcer, and gastric malignancy. Numerous patients have received H. pylori eradication treatment, but only 1–2% of H. pylori-infected individuals ultimately develop gastric cancer. Recently, numerous epidemiological and basic experimental studies suggested a role for chronic H. pylori infection in protecting against inflammatory bowel disease (IBD) by inducing systematic immune tolerance and suppressing inflammatory responses. Here we summarize the current research progress on the association between H. pylori and IBD, and further describe the detailed molecular mechanism underlying H. pylori-induced dendritic cells (DCs) with the tolerogenic phenotype and immunosuppressive regulatory T cells (Tregs). Based on the potential protective role of H. pylori infection on IBD, we suggest that the interaction between H. pylori and the host is complicated, and H. pylori eradication treatment should be administered with caution, especially for children and young adults.

Helicobacter pylori infection is a major risk factor for the development of gastric cancer. Aberrant expression of microRNAs is strongly implicated in gastric tumorigenesis; however, their contribution in response to H. pylori infection has not been fully elucidated. In this study, we evaluated the expression of miR‐135b‐5p and its role in gastric cancer. We describe the overexpression of miR‐135b‐5p in human gastric cancer tissue samples compared with normal tissue samples. Furthermore, we found that miR‐135b‐5p is also up‐regulated in gastric tumors from the trefoil factor 1‐knockout mouse model. Infection with H. pylori induced the expression of miR‐135b‐5p in the in vitro and in vivo models. miR‐135b‐5p induction was mediated by NF‐κB. Treatment of gastric cancer cells with TNF‐α induced miR‐135b‐5p in a NF‐κB–dependent manner. Mechanistically, we found that miR‐135b‐5p targets Krüppel‐like factor 4 (KLF4) and binds to its 3′ UTR, leading to reduced KLF4 expression. Functionally, high levels of miR‐135b‐5p suppress apoptosis and induce cisplatin resistance. Our results uncovered a mechanistic link between H. pylori infection and miR‐135b‐5p‐KLF4, suggesting that targeting miR‐135b‐5p could be a potential therapeutic approach to circumvent resistance to cisplatin.—Shao, L., Chen, Z., Soutto, M., Zhu, S., Lu, H., Romero‐Gallo, J., Peek, R., Zhang, S., El‐Rifai, W. Helicobacter pylori‐induced miR‐135b‐5p promotes cisplatin resistance in gastric cancer. FASEB J. 33, 264–274 (2019). www.fasebj.org

Esophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer‐associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs‐derived exosomes have a role in the progression of ESCC is largely unknown. Here, we find that Sonic Hedgehog (SHH) is highly expressed in CAFs lysis solution, conditioned medium of cultured CAFs (CAF‐CM) and CAFs‐derived exosomes, and esophageal cancer cell lines educated by CAF‐CM and CAFs‐derived exosomes can improve their growth and migration abilities in vitro and in vivo. Besides, those effects can be partly neutralized by cyclopamine, inhibitor of the Hedgehog signaling pathway. Thus, our research elucidates the crucial role of CAFs‐derived exosomes in the growth and progression of ESCC, and may open up new avenues in the treatment of ESCC.

Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification inASPNgene. Both higher ASPN expression levels andASPNCNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-β/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-β signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-β/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.