Correction to: Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer.

An amendment to this paper has been published and can be accessed via the original article.

Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer.

BACKGROUND: Oxaliplatin resistance is a major challenge for treatment of advanced colorectal cancer (CRC). Both acquisition of epithelial-mesenchymal transition (EMT) and suppressed drug accumulation in cancer cells contributes to development of oxaliplatin resistance. Aberrant expression of small noncoding RNA, miR-128-3p, has been shown to be a key regulator in tumorigenesis and cancer development. However, its roles in the progression of CRC and oxaliplatin-resistance are largely unknown. METHODS: Oxaliplatin-resistant CRC and normal intestinal FHC cells were transfected with a miR-128-3p expression lentivirus. After transfection, FHC-derived exosomes were isolated and co-cultured with CRC cells. miR-128-3p expression in resistant CRC cells, FHC cells, and exosomes was quantified by quantitative real-time PCR (RT-qPCR). The mRNA and protein levels of miR-128-3p target genes in resistant CRC cells were quantified by RT-qPCR and western blot, respectively. The effects of miR-128-3p on CRC cell viability, apoptosis, EMT, motility and drug efflux were evaluated by CCK8, flow cytometry, Transwell and wound healing assays, immunofluorescence, and atomic absorption spectrophotometry. Xenograft models were used to determine whether miR-128-3p loaded exosomes can re-sensitize CRC cells to oxaliplatin in vivo. RESULTS: In our established stable oxaliplatin-resistant CRC cell lines, in vitro and vivo studies revealed miR-128-3p suppressed EMT and increased intracellular oxaliplatin accumulation. Importantly, our results indicated that lower miR-128-3p expression was associated with poor oxaliplatin response in advanced human CRC patients. Moreover, data showed that miR-128-3p-transfected FHC cells effectively packaged miR-128-3p into secreted exosomes and mediated miR-128-3p delivery to oxaliplatin-resistant cells, improving oxaliplatin response in CRC cells both in vitro and in vivo. In addition, miR-128-3p overexpression up-regulated E-cadherin levels and inhibited oxaliplatin-induced EMT by suppressing Bmi1 expression in resistant cells. Meanwhile, it also decreased oxaliplatin efflux through suppressed expression of the drug transporter MRP5. CONCLUSION: Our results demonstrate that miR-128-3p delivery via exosomes represents a novel strategy enhancing chemosensitivity in CRC through negative regulation of Bmi1 and MRP5. Moreover, miR-128-3p may be a promising diagnostic and prognostic marker for oxaliplatin-based chemotherapy.

Preparation and evaluation of isoliquiritigenin-loaded F127/P123 polymeric micelles.

Isoliquiritigenin (ISL) possesses a variety of pharmacological activities amid poor solubility in water which has restricted its clinical application. In this study, isoliquiritigenin-loaded F127/P123 polymeric micelles (ISL-FPM) were successfully prepared and evaluated in vitro and in vivo. The particle size, polydispersity index, and zeta potential of the selected formulation were 20.12 ± 0.72 nm, 0.183 ± 0.046, and -38.31 ± 0.33 mV, respectively, coupled with high encapsulation efficiency of 93.76 ± 0.31%. Drug-loading test showed the solubility of ISL after formulating into micelles was 232 times higher than its intrinsic solubility. Moreover, critical micelle concentration (CMC) was tested with fluorescence probe method and turned out to be quite low, which implied high stability of ISL-FPM. Release profile in HCl (pH 1.2), double distilled water, and PBS (pH 7.4) of ISL-FPM reached over 80%, while free ISL was around 40%. Pharmacokinetic research revealed that formulated ISL-FPM significantly increased bioavailability by nearly 2.23-fold compared to free ISL. According to the results of in vitro antioxidant activity, scavenging DPPH activity of ISL was significantly strengthened when it was loaded into polymeric micelles. Altogether, ISL-FPM can act as a promising approach to improve solubility as well as enhance bioavailability and antioxidant activity of ISL.

The characterisation, pharmacokinetic and tissue distribution studies of TPGS modified myricetrin mixed micelles in rats.

This study was designed to investigate the bioavailability and targeting of myricetrin-loaded ternary micelles modified with and without TPGS. The particle diameters of myricetrin-loaded micelles and myricetrin-loaded-TPGS micelle were 30.93 ± 1.34 nm and 26.42 ± 0.89 nm, respectively, while their respective encapsulation efficiencies (m/m, %) were 83.3 ± 1.08 and 93.8 ± 1.18. The release rate of myricetrin in the micellar system clearly exceeded the free myricetrin in the three media (pH 6.8 phosphate buffer, pH 1.2 HCl solution and double distilled water). In vivo studies displayed that the bioavailability of myricetrin mixed micelles was remarkably improved than the free drug after oral administration. Moreover, the results of tissue distribution showed that myricetrin-loaded-TPGS micelles accumulated well in the liver tissue. Based on these results, it was speculated that myricetrin-loaded-TPGS micelles might act as a promising carrier for liver targeting with improved hepatic concentration of myricetrin compared with the myricetrin-loaded micelles.

Cell-free lncRNA expression signatures in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer.

Cell-free long non-coding RNAs (lncRNAs) are stably present in urine and can serve as non-invasive biomarkers for cancer. We aimed to identify signatures of lncRNAs in urine for diagnosis and prognosis of bladder cancer (BC). Screening of lncRNAs by microarray analysis was performed using urine samples of 10 BC patients and 10 controls. Expressions of candidate lncRNAs were evaluated in the training and validation set including 230 BC patients and 230 controls by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A two-lncRNA panel (uc004cox.4 and GAS5) was constructed and provided high diagnostic accuracy of BC with an area under the curve (AUC) of 0.885 (95% CI, 0.836-0.924). The AUCs of the lncRNA panel for Ta, T1 and T2-T4 were 0.843, 0.867 and 0.923, respectively, significantly higher than those of urine cytology (all P < .05). Kaplan-Meier analysis revealed that higher level of uc004cox.4 was associated with poor recurrence-free survival (RFS) of non-muscle invasive BC (NMIBC) (P = .008). Additionally, Cox regression analysis indicated that uc004cox.4 was an independent prognostic factor for RFS of NMIBC (P = .018). Taken together, our findings indicated that urinary lncRNA signatures possessed potential clinical value for BC diagnosis. Moreover, uc004cox.4 could provide prognostic information for NMIBC.

Poland syndrome combined with breast cancer: a case report.

Background: Poland syndrome is an occasional congenital malformation characterized by unilateral chest wall dysplasia and ipsilateral upper limb abnormalities. An association between Poland syndrome and breast cancer has been reported, but no clear etiological link between Poland syndrome and breast tumors has been established. We report a case of Poland syndrome combined with breast cancer and analyzed the clinical features of breast cancer in this case and its influence on the choice of treatment for breast cancer. Case Description: In February 2022, we admitted a 47-year-old woman with Poland syndrome involving the right limb combined with right-sided breast cancer. After admission, the patient was given eight cycles of neoadjuvant therapy and underwent a modified radical mastectomy on September 7, 2022. Absence of right pectoralis major muscle and pectoralis minor muscle, thoracic deformity, and an adhesive band along the side of the sternum to the right axilla were observed during the operation. After surgery, the incision achieved grade-A healing, and the targeted therapy was continued for 1 year. The patient was followed up for 8 months after surgery, and the limb function of the affected side recovered well, and no obvious subcutaneous effusion, flap necrosis, upper limb edema, and other complications were observed. Conclusions: The anatomic variation of patients with Poland syndrome has some influence on the selection of surgical methods for breast cancer, but whether it would affect the prognosis of patients is unknown. To clarify the relationship between Poland syndrome and breast cancer, we need more cases to conduct etiological studies in the future.

Latest advances and perspectives of liquid biopsy for cancer diagnostics driven by microfluidic on-chip assays.

Microfluidic-based lab-on-a-chip technology is a multidisciplinary approach, which has evolved rapidly in the past decade and remains a hot research topic as a promising microanalysis platform for a plethora of biomedical applications. Microfluidic chips have been successfully applied in cancer diagnosis and monitoring, given that they can lead to the effective separation and analysis of cancer-derived substances such as extracellular vesicles (EVs), circulating tumour cells (CTCs) and circulating DNA (ctDNA), proteins and other metabolites. In particular, EVs and CTCs are two outstanding objects for cancer liquid biopsy, which share similar membrane structures but possess different sizes. Through molecular typing and concentration detection of EVs, CTCs and ctDNA, disease-related information can be well-learned, including the development stage and prognosis of cancer. However, the conventional separation and detection methods are often time-consuming with limited efficiency. In comparison, the use of microfluidic platforms can effectively simplify the separation and enrichment process and improve the detection efficiency significantly. Although review papers have been published on the application of microfluidic chips for the analysis of objects of liquid biopsy, generally they focused on a specific detection target, lacking a descriptive extraction of the commonality of LOC devices used in liquid biopsy. Thus, few of them present a comprehensive overview and outlook on the design and application of microfluidic chips for liquid biopsy. This motivated us to prepare this review paper, which is divided into 4 parts. The first part aims to elucidate the material selection and fabrication approaches of microfluidic chips. In the second part, the important separation strategies, including physical methods and biological methods, are discussed. The third part highlights the advanced on-chip technologies for the detection of EVs, CTCs and ctDNA by providing practical examples. In the fourth part, novel on-chip applications of single cells/exosomes are introduced. Finally, the prospective outlook and challenges for the long-term development of on-chip assays are envisioned and discussed.

Hollow Cu2-xSe-based nanocatalysts for combined photothermal and chemodynamic therapy in the second near-infrared window.

Chemodynamic therapy (CDT) and photothermal therapy (PTT) have gained popularity due to their non-invasive characteristics and satisfying therapeutic expectations. A Cu-based nanomaterial serving as a Fenton-like nanocatalyst for CDT together with a photothermal agent for simultaneous PTT seems to be a powerful strategy. In this work, the morphological effect of Cu2-xSe nanoparticles on CDT and PTT was systematically investigated. In particular, the hollow octahedral Cu2-xSe nanoparticles exhibited higher photothermal and chemodynamic performance than that of spherical or cubic Cu2-xSe nanoparticles in the second near-infrared (NIR-II) window. In addition, the octahedral Cu2-xSe nanoparticles were further loaded with the autophagy inhibitor chloroquine (CQ) and connected with the targeting neuropeptide Y ligand, and shown to work as a novel therapeutic platform (Cu2-xSe@CQ@NPY), holding an immense potential to achieve synergetic enhancement of CDT/PTT with a positive therapeutic outcome for breast cancer.

Stimuli-Responsive Codelivery System Self-Assembled from in Situ Dynamic Covalent Reaction of Macrocyclic Disulfides for Cancer Magnetic Resonance Imaging and Chemotherapy.

Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol-disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo. These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.

Prevalence, evolution, replication and transmission of H3N8 avian influenza viruses isolated from migratory birds in eastern China from 2017 to 2021.

The continued evolution and emergence of novel influenza viruses in wild and domestic animals poses an increasing public health risk. Two human cases of H3N8 avian influenza virus infection in China in 2022 have caused public concern regarding the risk of transmission between birds and humans. However, the prevalence of H3N8 avian influenza viruses in their natural reservoirs and their biological characteristics are largely unknown. To elucidate the potential threat of H3N8 viruses, we analyzed five years of surveillance data obtained from an important wetland region in eastern China and evaluated the evolutionary and biological characteristics of 21 H3N8 viruses isolated from 15,899 migratory bird samples between 2017 and 2021. Genetic and phylogenetic analyses showed that the H3N8 viruses circulating in migratory birds and ducks have evolved into different branches and have undergone complicated reassortment with viruses in waterfowl. The 21 viruses belonged to 12 genotypes, and some strains induced body weight loss and pneumonia in mice. All the tested H3N8 viruses preferentially bind to avian-type receptors, although they have acquired the ability to bind human-type receptors. Infection studies in ducks, chickens and pigeons demonstrated that the currently circulating H3N8 viruses in migratory birds have a high possibility of infecting domestic waterfowl and a low possibility of infecting chickens and pigeons. Our findings imply that circulating H3N8 viruses in migratory birds continue to evolve and pose a high infection risk in domestic ducks. These results further emphasize the importance of avian influenza surveillance at the wild bird and poultry interface.

A novel dual-function SERS-based identification strategy for preliminary screening and accurate diagnosis of circulating tumor cells.

Non-specific adsorption of bioprobes based on surface-enhanced Raman spectroscopy (SERS) technology inevitably endows white blood cells (WBC) in the peripheral blood with Raman signals, which greatly interfere the identification accuracy of circulating tumor cells (CTCs). In this study, an innovative strategy was proposed to effectively identify CTCs by using SERS technology assisted by a receiver operating characteristic (ROC) curve. Firstly, a magnetic Fe3O4-Au complex SERS bioprobe was developed, which could effectively capture the triple negative breast cancer (TNBC) cells and endow the tumor cells with distinct SERS signals. Then, the ROC curve obtained based on the comparison of SERS intensity of TNBC cells and WBC was used to construct a tumor cell identification model. The merit of the model was that the detection sensitivity and specificity could be intelligently switched according to different identification purposes such as accurate diagnosis or preliminary screening of tumor cells. Finally, the difunctional recognition ability of the model for accurate diagnosis and preliminary screening of tumor cells was further validated by using the healthy human blood added with TNBC cells and blood samples of real tumor patients. This novel difunctional identification strategy provides a new perspective for identification of CTCs based on the SERS technology.

Effective Separation of Cancer-Derived Exosomes in Biological Samples for Liquid Biopsy: Classic Strategies and Innovative Development.

Liquid biopsy has remarkably facilitated clinical diagnosis and surveillance of cancer via employing a non-invasive way to detect cancer-derived components, such as circulating tumor DNA and circulating tumor cells from biological fluid samples. The cancer-derived exosomes, which are nano-sized vesicles secreted by cancer cells have been investigated in liquid biopsy as their important roles in intracellular communication and disease development have been revealed. Given the challenges posed by the complicated humoral microenvironment, which contains a variety of different cells and macromolecular substances in addition to the exosomes, it has attracted a large amount of attention to effectively isolate exosomes from collected samples. In this review, the authors aim to analyze classic strategies for separation of cancer-derived exosomes, giving an extensive discussion of advantages and limitations of these methods. Furthermore, the innovative multi-strategy methods to realize efficient isolation of cancer-derived exosomes in practical applications are also presented. Additionally, the possible development trends of exosome separation in to the future is discussed in this review.

A TiO2-based bioprobe enabling excellent SERS activity in the detection of diverse circulating tumor cells.

Circulating tumor cells (CTCs) can be the seeds of tumor metastasis and are closely linked to cancer-related death. Fast and effective detection of CTCs is important for the early diagnosis of cancer and the evaluation of micrometastasis. However, the extreme rarity and heterogeneity of CTCs in peripheral blood make sensitive detection of CTCs a big challenge. In this paper, a TiO2-based surface-enhanced Raman scattering (SERS) bioprobe is reported for the first time with outstanding ultrasensitive specificity, excellent stability of the signal, and good biocompatibility for the detection of CTCs. The TiO2 NPs were encoded with alizarin red (AR) and functionalized with reduced bovine serum protein (rBSA) and folic acid (FA). The limit of detection (LOD) for 4-mercaptobenzoic acid (4-MBA) and AR molecules adsorbed on the TiO2 SERS substrate is 5 × 10-7 M. The designed TiO2-based SERS bioprobe can be effectively utilized in detecting four diverse types of cancer cells in rabbit blood, which shows good sensitivity of the SERS detection technology. Finally, precise targeting of CTCs based on the SERS bioprobe with the function of fluorescence imaging is also confirmed by the fluorescence colouration test. This work offers a novel strategy for CTC detection and the development of non-noble metal semiconductor-based SERS platforms for tumor diagnosis.

Ultrahigh SERS activity of the TiO2@Ag nanostructure leveraged for accurately detecting CTCs in peripheral blood.

Circulating tumor cells (CTCs) usually shed from primary and metastatic tumors serve as an important tumor marker, and easily cause fatal distant metastasis in cancer patients. Accurately and effectively detecting CTCs in a peripheral blood sample is of great significance in early tumor diagnosis, efficacy evaluation, and postoperative condition monitoring. In this work, a TiO2@Ag nanostructure is structured as a SERS substrate, rhodamine 6G (R6G) is used as a Raman signal molecule, the reduced bovine serum protein (rBSA) acts as a protective agent, and folic acid (FA) acts as a target molecule to specifically recognize cancer cells. A TiO2@Ag-based SERS bioprobe is successfully prepared with the feature of ultrahigh sensitivity, good specificity, low toxicity, and high accuracy in CTC detection. The remarkable SERS activity of the TiO2@Ag nanostructure is synergistically contributed by surface plasmon resonance and photon-induced charge transfer mechanism. The limit of detection for rhodamine 6G (R6G) molecules adsorbed on the TiO2@Ag SERS substrate is 5 × 10-14 M, and the corresponding SERS enhancement factor can reach 7.61 × 107. The designed TiO2@Ag-R6G-rBSA-FA SERS bioprobe is effectively utilized in detecting various cancer cells in rabbit blood, and the limit of detection (LOD) for the target cancer cell is 1 cell per mL. Notably, CTCs in peripheral blood of six clinical liver cancer patients are successfully recognized via the TiO2@Ag-based SERS bioprobe. Accurately recognizing CTCs in peripheral blood based on the TiO2@Ag-R6G-rBSA-FA SERS bioprobe is also carefully verified by in situ immunofluorescence staining experiments, which directly supports the CTC detection accuracy of the SERS strategy. These results demonstrate that the TiO2@Ag-based SERS bioprobe has great application potential in early screening and diagnosis of tumors.

A defect-rich ultrathin MoS2/rGO nanosheet electrocatalyst for the oxygen reduction reaction.

The structural properties such as high specific surface area, good electrical conductivity, rich-defects of the catalyst surface guarantee outstanding catalytic performance and durability of oxygen reduction reaction (ORR) electrocatalysts. It is still a challenging task to construct ORR catalysts with excellent performance. Herein, we have reported column-like MoS2/rGO with defect-rich ultrathin nanosheets prepared by a convenient solvothermal method. The structure and composition of MoS2/rGO are systematically investigated. MoS2/rGO shows a remarkable electrocatalytic performance, which is characterized by an outstanding onset potential of 0.97 V, a half-wave potential of 0.83 V, noticeable methanol tolerance, and durability of 93.7% current retention, superior to commercial Pt/C. The ORR process occurring on MoS2/rGO is a typical four electron pathway. Therefore, this study achieves the design of a low-cost, highly efficient and stable nonprecious metal ORR electrocatalyst in alkaline media.

GSH responsive nanomedicines self-assembled from small molecule prodrug alleviate the toxicity of cardiac glycosides as potent cancer drugs.

Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect. Using periplocymarin (PPM) as a target agent, we designed a novel redox-responsive prodrug conjugated with linoleic acid (PPM-ss-LA), which was capable of self-assembling independent of exogenous excipients. This prodrug could co-assemble with DSPE2k to form PEGylated prodrug nanoparticles (PPM-ss-LA/DSPE2k-NPs) with enhanced colloidal stability and blood circulation. Compared with free PPM, PPM-ss-LA/DSPE2k-NPs retained high anti-proliferative activity and showed increased cell uptake and therapeutic efficacy. Furthermore, the PPM-ss-LA/DSPE2k-NPs acquired a greatly enhancement of 50% lethal dose (LD50) in mice and reduced system toxicity compared with the free drug. Overall, the on-demand release of nanoprodrug delivery system could improve the therapeutic window and anticancer efficacy of CGs.

Evaluation of Serum Exosomal lncRNAs as Diagnostic and Prognostic Biomarkers for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Exosomal long non-coding RNAs (lncRNAs) have been recognised as promising stable biomarkers in cancers. The aim of this study was to identify an exosomal lncRNA panel for diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Exosomes were isolated from serum by ExoQuick Solution. To validate the exosomes, exosomal markers and characterization of nanoparticle were performed. Quantitative real-time PCR was used to measure the levels of lncRNAs in exosomes from ESCC patients and healthy subjects. In the training set, exosomal lncRNA profiles from 404 samples were conducted and established new models by multivariate logistic regression. In the validation set, the diagnostic performance of the panel was further validated in 222 additional individuals with a receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox proportional hazards analysis were applied to assess the correlation between lncRNAs and survival rate of ESCC patients. RESULTS: A 4-lncRNA panel (UCA1, POU3F3, ESCCAL-1 and PEG10) in exosomes for ESCC diagnosis was developed by logistic regression model. The diagnostic accuracy of panel was evaluated with AUC value of 0.844 and 0.853 for training and validation stage, respectively. The corresponding AUCs for patients with TNM stage I-II and III were 0.820 and 0.935, significantly higher than squamous cell carcinoma antigen (P<0.001), which were 0.652 and 0.642, respectively. Kaplan-Meier analysis indicated that patients with higher level of UCA1 and POU3F3 had lower survival rate (P<0.001). Additionally, POU3F3 might be as an independent prognostic factor for ESCC patients (P=0.004). CONCLUSION: These findings suggested that serum exosomal 4-lncRNA panel has considerable value for ESCC diagnosis, and POU3F3 may serve as a novel and independent prognostic predictor in clinical applications.

Unique metastasis-associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma.

BACKGROUND: Local relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis-associated lncRNAs in patients with lung adenocarcinoma (LUAD). METHODS: Firstly, the potential metastasis-associated lncRNAs were identified by analyzing high-throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis-associated function of these six lncRNAs was confirmed by lncRNA over-expression or depletion and in vitro transwell assays in LUAD cells. RESULTS: An lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649-AS1, HNF4A-AS1, FAM222A-AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse-free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility. CONCLUSIONS: This novel six-lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients. KEY POINTS: Significant findings of the study The unique metastasis-associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study adds This signature had considerable prognostic value for prediction of relapse in LUAD patients.

Circulating long non-coding RNA colon cancer-associated transcript 2 protected by exosome as a potential biomarker for colorectal cancer.

BACKGROUND: Colon cancer-associated transcript 2 (CCAT2) plays a crucial role in several cancers. However, the clinical significance of circulating CCAT2 expression in colorectal cancer (CRC) has not previously been elucidated. In this study, we aimed to elucidate the potential role of CCAT2 and its clinical significance of circulating expression level in CRC. METHODS: We detected the expression of CCAT2 in 75 pairs of tumorous and adjacent non-tumorous tissues derived from CRC patients by quantitative real-time polymerase chain reaction. The serum levels of CCAT2 expression were detected in an independent cohort of healthy controls and CRC patients. We analyzed the relationship between CCAT2 levels in serum and clinicopathological features of CRC patients. We also compared CCAT2 levels in paired pre-operative and post-operative serum samples. Furthermore, the existence of serum CCAT2 in exosomes was investigated. RESULTS: The levels of CCAT2 expression were significantly over-expressed in tumor tissues (p < 0.05) compared to adjacent non-tumorous tissues. Higher CCAT2 expression was associated with advanced CRC patients. Moreover, the serum levels of CCAT2 expression were significantly over-expressed in CRC patients (p < 0.05) compared to those in healthy subjects. In addition, the CCAT2 levels were significantly decreased in post-operative samples than those in pre-operative ones (P = 0.01). We also found that CCAT2 expression was up-regulated in CRC exosomes (P < 0.001) and no significant differences of CCAT2 levels were found between in serum and in exosomes. CONCLUSIONS: Our data indicate that circulating CCAT2 which might protected by exosomes can serve as a novel potential predictor in CRC.