Long noncoding RNA HOTTIP plays important roles in the generation and progression of human cancers. Exosomes participate in cellular communication by transmitting moleculars between cells and are regarded as suitable candidates for non-invasive diagnosis. However, the existence of HOTTIP in the circulating exosomes and the potential roles of exosomal HOTTIP in gastric cancer (GC) was poorly understood. This study aims at investigating the clinical roles of exosomal HOTTIP in GC. Serum exosomal HOTTIP from 246 subjects (126 GC patients and 120 healthy people) were detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that expression levels of exosomal HOTTIP were typically upregulated in GC than in normal control (P < 0.001). And its expression levels were significantly correlated with invasion depth (P = 0.0298) and TNM stage (P < 0.001). The AUC for exosomal HOTTIP was 0.827, which demonstrated a higher diagnostic capability than CEA, CA 19–9 and CA72–4 (AUC = 0.653, 0.685 and 0.639, respectively) (P < 0.001). The Kaplan–Meier analysis showed a correlation between increased exosomal HOTTIP levels and poor overall survival (OS) (logrank P < 0.001). And univariate and multivariate COX analysis revealed exosomal HOTTIP overexpression was an independent prognostic factor in GC patients (P = 0.027). These findings demonstrated that exosomal HOTTIP may be a potential biomarker for GC in diagnosis and prognosis.

Immune inhibitory receptors play an important role in organ transplantation, autoimmune diseases and cancers. Immunoglobulin-like transcript (ILT)2 and ILT3 belong to the inhibitory receptors of the ILT family, which have been reported to regulate a broad range of cellular functions involved in the immune response. They contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which are related to immune regulation. Although ILT receptors have been studied in dendritic cells (DCs), T cells, NK cells and other cell types, the expression and clinical significance of ILT2 and ILT3 in gastric cancer have yet to be elucidated. Here, the expression of ILT2 and ILT3 in gastric cancer cell lines and pathologic tissues, as well as their effects on the cytotoxicity of NK92MI against the gastric cancer cell lines MKNI with ILT2lowILT3low and HGC-27 with ILT2highILT3high were detected. The results suggest that ILT2 and ILT3 are expressed with diverse degrees in gastric cancer cells and tissues, and the expression of ILT2 is related with differentiation and size of tumors. Furthermore, the cytotoxic activity of NK92MI against the MKNI cell line was stronger than that against HGC-27. This study indicates that ILT2 and ILT3 play a key role in gastric cancer immune escape, and ILT2 may be a new target in the clinical diagnosis and treatment of gastric cancer.

Aberrance in the blood bacterial microbiome has been identified and validated in several non-infectious diseases, including cancer. The occurrence and progression of gastric cancer has been found to be associated with alterations in the microbiome composition. However, the composition of the blood microbiome in patients with gastric cancer is not well-characterized. To test this hypothesis, we conducted a case-control study to investigate the microbiota compositions in the serum of patients with gastric cancer. The serum microbiome was investigated in patients with gastric cancer, atypical hyperplasia, chronic gastritis, and in healthy controls using 16S rRNA gene sequencing targeting the V1-V2 region. Our results revealed that the structure of the serum microbiome in gastric cancer was significantly different from all other groups, and alpha diversity decreased from the healthy control to patients with gastric cancer. The serum microbiome correlated significantly with tumor-node-metastasis (TNM) stage, lymphatic metastasis, tumor diameter, and invasion depth in gastric cancer. Three genera or species, namely, Acinetobacter, Bacteroides, Haemophilus parainfluenzae, were enriched in patients with gastric cancer, whereas Sphingomonas, Comamonas, and Pseudomonas stutzeri were enriched in the healthy control. Furthermore, the structure of serum microbiota differed between gastric cancer lymphatic metastasis and non-lymphatic metastasis. As a pilot investigation to characterizing the serum microbiome in gastric cancer, our study provided a foundation for improving our understanding of the role of microbiota in the pathogenesis of gastric cancer.

Cisplatin is the first‐line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy‐dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR‐508‐3p/Bcl‐2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer‐derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn‐GCEx) secreted from Fn‐infected GC cells remains unclear. In this study, Fn‐GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn‐GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn‐GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)‐885‐3p, thus activating the PI3K/AKT pathway in Fn‐GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR‐885‐3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.

Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.