Recently, expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. In this study, we aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to screen and evaluate the expressions of eight candidate lncRNAs in a training set (208 urine samples) and a validation set (160 urine samples). A panel consisting of three differently expressed lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) was established for BC diagnosis in the training set, showing an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.854. Subsequently, the performance of the panel was further verified with an AUC of 0.813 in the validation set, which was significantly higher than that of urine cytology (0.619). In addition, Kaplan-Meier analysis suggested that the up-regulation of PCAT-1 and MALAT1 was associated with poor recurrence-free survival (RFS) of non-muscle-invasive BC (NMIBC) (p < 0.001 and p = 0.002, respectively), and multivariate Cox proportional hazards regression analysis revealed that exosomal PCAT-1 overexpression was an independent prognostic factor for the RFS of NMIBC (p = 0.018). Collectively, our findings indicated that UE-derived lncRNAs possessed considerable clinical value in the diagnosis and prognosis of BC.

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC.

Circulating lncRNAs have emerged as promising biomarkers for the diagnosis of various cancers. This study aimed to establish an accurate risk prediction model based on serum lncRNAs to facilitate the detection of prostate cancer (PCA). RT‐qPCR was used to analyse the levels of candidate lncRNAs, and four lncRNAs (NEAT1, ARLNC1, FOXP4‐AS1 and DSCAM‐AS1) were identified to be differently expressed in serum from 190 PCA patients, 140 benign controls, and 170 healthy controls. A ProsRISK score based on four lncRNAs and prostate‐specific antigen (PSA) was established in the training set. ROC analysis in the validation set revealed that the ProsRISK demonstrated more powerful capacity in discriminating PCA from healthy and benign controls, with an AUC of 0.926 (95% CI: 0.882–0.970) and 0.837 (95% CI: 0.770–0.904), which were significantly higher than those of the lncRNA panel or PSA alone (all at p < 0.05). Moreover, the ProsRISK showed good diagnostic performance for PCA I–II patients compared with healthy and benign controls, and the corresponding AUCs were 0.905 (95% CI: 0.843–0.968) and 0.819 (95% CI: 0.732–0.907). Our findings indicated that the constructed ProsRISK could be a reliable risk stratification model and have great potential for clinical use to improve the precision surveillance for PCA.

Background: Preoperative determination of muscular infiltration is crucial for appropriate treatment planning in patients with muscle-invasive bladder cancer (MIBC). We aimed to explore early diagnostic biomarkers in serum for MIBC in this study.Methods: The expression profiles of long noncoding RNA (lncRNA) were initially screened by high-throughput sequencing and evaluation of potential lncRNAs were conducted by two phases of RT-qPCR assays using serum samples from 190 patients with MIBC and 190 non-muscle-invasive BC (NMIBC) patients. Multivariate logistic regression analysis was applied to establish a diagnostic signature with high accuracy and Fagan’s nomogram was plotted to promote clinical application. Bioinformatics analysis was used to determine the potential miRNA-mRNA binding of candidate lncRNAs.Results: We identified three differentially expressed lncRNAs (LINC00565, LINC00592 and NDUFA6-AS1) and established a 3-lncRNA panel which demonstrated high diagnostic accuracy for MIBC with an AUC of 0.903 (95% CI: 0.850-0.942) and 0.875 (95% CI: 0.802-0.928) in the training and validation set. Moreover, construction and assessment of Fagan’nomogram demonstrated that the 3-lncRNA panel could exhibit practical and helpful values for clinical use. Finally, a network map based on LINC00565 was constructed and we found that the expression of miR-143-5p and miR-4516 were significantly correlated with LINC00565 in MIBC.Conclusion: Our findings indicated that the constructed 3-lncRNA panel in serum showed favorable diagnostic capacity and might serve as promising non-invasive biomarkers in the early diagnosis of MIBC.