Exosomes are emerging as a new type of cancer biomarkers. Exosome is a bilayered nano-sized vesicle secreted by various living cells in all body fluids. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by cells and cancer cell-specific molecular and genetic contents, exosomes are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of cancer cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma correlate with pathological processes of many diseases including cancer. However, previous studies on exosome application in cancer diagnosis and treatment mainly focussed on miRNAs. With the development of rapid large-scale production, purification, extraction and screening of exosomal contents, exosomal protein application can be explored for early stage cancer diagnosis, monitoring and prognosis evaluation. Here, we summarized the recent developments in application of exosomal proteins for cancer diagnosis.

BackgroundAlthough gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs.MethodsWe first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3’ untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients’ response to gemcitabine.ResultsA549-GR–derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients.ConclusionOur data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0694-8) contains supplementary material, which is available to authorized users.

Our results demonstrated that miR-92a induced EMT and regulated cell growth, migration and invasion in the SW480 cells, at least partially, via suppression of PTEN expression. MiR-92a may serve as a novel therapeutic target in colorectal cancer.

This study revealed that miR-92a overexpression was correlated with specific colorectal cancer biopathologic features, such as TNM stage, lymph node and distant metastases, and poor survival of the patients, indicating that miR-92a may serve as a molecular prognostic marker for colorectal cancer and disease progression.

BackgroundMicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored.MethodsQuantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene.ResultsIn this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin.ConclusionsIn conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer.

Human microRNA-155 (miR-155) has been demonstrated to regulate a variety of cellular functions, including epithelial-to-mesenchymal transition (EMT) by targeting multiple messenger RNAs (mRNAs). However, its role in colorectal cancer (CRC) remains unelucidated. Therefore, the aim of the present study was to investigate the effects of miR-155 on CRC cells. The expression level of miR-155 was quantified by quantitative real-time reverse transcriptase-PCR (qRT-PCR) in primary CRC tissues and normal adjacent mucosa. MTT, migration and invasion assays were used to examine the proliferation, migration and invasion of SW480 cells transfected with miR‑155. The expression of miR-155 was significantly upregulated in the CRC tissues and the high expression of miR-155 correlated with an advanced clinical stage, lymph node and distant metastases. The ectopic expression of miR-155 enhanced the migration and invasive ability of the SW480 cells and altered their morphological appearance; however, cell proliferation was not affected. E-cadherin expression levels decreased, while ZEB1 expression levels increased in the SW480 cells overexpressing miR-155. Furthermore, the overexpression of miR-155 upregulated claudin-1 expression. Thus, our data suggest that miR-155 plays an important role in promoting CRC cell migration and invasion, at least in part through the regulation of claudin-1 expression and controlling metastasis in CRC.

Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to promote invasion and metastasis in several types of human cancer and to have a prognostic role in certain cancers. However, the clinical significance of ZEB1 in colorectal cancer (CRC) has not been sufficiently investigated. This study aimed to address this issue. In this study, we compared the expression of ZEB1 between CRC tissues and normal adjacent mucosa using quantitative real-time RT-PCR. The association of ZEB1 expression with clinicopathological characteristics was analyzed by appropriate statistical analyses. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association of ZEB1 expression with survival of patients. The results showed that the relative expression levels of ZEB1 were significantly higher in CRC tissues compared to the normal adjacent mucosa and higher expression of ZEB1 correlated with liver metastasis. Kaplan-Meier analysis indicated that patients with high ZEB1 had a poor overall survival. Moreover, the multivariate analysis showed that high expression of ZEB1 was an independent predictor of overall survival. Our data indicate the potential of ZEB1 as a novel prognostic biomarker for CRC.

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