Long non-coding RNAs (lncRNAs) can serve as blood-based biomarkers for cancer detection. To identify novel lncRNA biomarkers for gastric cancer (GC), we conducted, for the first time, genome-wide lncRNA screening analysis in two sets of samples: five paired preoperative and postoperative day 14 plasma samples from GC patients, and tissue samples from tumor and adjacent normal tissues. Candidate tumor-related lncRNAs were then quantitated and evaluated in three independent phases comprising 321 participants. The expression levels of lncRNAs were also measured in GC cell lines and the corresponding culture medium. Biomarker panels, lncRNA-based Index I and carcinoembryonic antigen (CEA)-based Index II, were constructed using logistic regression, and their diagnostic performance compared. Fagan's nomogram was plotted to facilitate clinical application. As a result, we identified five novel plasma lncRNAs (TINCR, CCAT2, AOC4P, BANCR and LINC00857), which, when combined in the lncRNA-based Index I, outperformed the CEA-based Index II (P < 0.001) and could distinguish GC patients from healthy controls with an area under the receiver-operating curve (AUC) of 0.91 (95% confidence interval (CI): 0.88-0.95). The lncRNA-based index decreased significantly by postoperative day 14 (P = 0.016), indicating its ability to monitor tumor dynamics. High values of the lncRNA-based index were correlated with tumor size (P = 0.036), depth of invasion (P = 0.025), lymphatic metastasis (P = 0.012) and more advanced tumor stages (P = 0.003). The lncRNA-based index was also able to discriminate GC patients from precancerous individuals and patients with gastrointestinal stromal tumor with AUC values of 0.82 (95% CI: 0.71-0.92) and 0.80 (95% CI: 0.68-0.91), respectively. Taken together, our findings demonstrate that this panel of five plasma lncRNAs could serve as a set of novel diagnostic biomarkers for GC detection.
Eph receptor tyrosine kinases and their ephrin ligands are involved in various signalling pathways and mediate critical steps of a wide variety of physiological and pathological processes. Increasing experimental evidence demonstrates that both Eph receptor and ephrin ligands are overexpressed in a number of human tumours, and are associated with tumour growth, invasiveness and metastasis. In this regard, the Eph/ephrin system provides the foundation for potentially exciting new targets for anticancer therapies for Eph-expressing tumours. The purpose of this review is to outline current advances in the role of Eph receptors and ephrin ligands in cancer, and to discuss novel therapeutic approaches of anticancer therapies.
IMPORTANCE The gastric cancer (GC)-associated long noncoding RNA1 (lncRNA-GC1) plays an important role in gastric carcinogenesis. However, exosomal lncRNA-GC1 and its potential role in GC are poorly understood. OBJECTIVE To evaluate the diagnostic value of circulating exosomal lncRNA-GC1 for early detection and monitoring progression of GC. DESIGN, SETTING, AND PARTICIPANTS We performed a multiphase investigation of circulating exosomal lncRNA-GC1 for early detection of GC involving consecutive patients with GC (n = 522), patients with gastric precancerous lesions (n = 85), and healthy donor individuals (HDs; n = 219) from December 2016 to February 2019 at Chinese People's Liberation Army General Hospital, China. LncRNA-GC1 was measured by reverse transcription-polymerase chain reaction by independent researchers who had no access to patients' information. Receiver operating characteristic curves were used to calculate diagnostic efficiency in comparison between lncRNA-GC1 and 3 traditional biomarkers (carcinoembryonic antigen [CEA], cancer antigen 72-4 [CA72-4], and CA19-9). MAIN OUTCOMES AND MEASURES Assessment of diagnostic efficiency on the basis of area under curve (AUC), specificity, and sensitivity. RESULTS Of the 826 patients included in the study, 508 were men (61.5%), and the median age of all patients was 60 years (range, 28-82 years). In the test phase, lncRNA-GC1 achieved better diagnostic performance than the standard biomarkers CEA, CA72-4, and CA19-9 (AUC = 0.9033) for distinguishing between the patients with GC and HDs. Additionally, exosomal lncRNA-GC1 levels were significantly higher in culture media from GC cells compared with those of normal gastric epithelial cells (t = 5.310; P = .002). In the verification phase, lncRNA-GC1 retained its diagnostic efficiency in discriminating patients with GC from those with gastric precancerous lesions as well from HDs. Moreover, lncRNA-GC1 exhibited a higher AUC compared with those of CEA, CA72-4, and CA19-9 for early detection of GC with sufficient specificity and sensitivity, especially for patients with GC with negative standard biomarkers. Moreover, the levels of circulating exosomal lncRNA-GC1 were significantly associated with GC from early to advanced stages (HD vs stage I, t = 20.98; P < .001; stage I vs stage II, t = 2.787; P = .006; stage II vs stage III, t = 4.471; P < .001; stage III vs stage IV, t = 1.023; P = .30), independent of pathological grading and Lauren classification (pathological grading: HD vs G1, t = 21.09; P < .001; G1 vs G2, t = 0.3718; P = .71; G2 vs G3, t = 0.3598; P = .72; Lauren classification: t = 24.81; P <.001). In the supplemental phase, the levels of circulating exosomal lncRNA-GC1 were consistent with those in GC tissues and cells and were higher compared with those in normal tissues and cells. Furthermore, the levels of circulating lncRNA-GC1 were unchanged after exosomes were treated with RNase and remained constant after prolonged exposure to room temperature or after repeated freezing and thawing (t = 1.443; P = ....
BackgroundLgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) has recently been identified as an intestinal stem cell marker. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated whether Lgr5 expression correlated with Ki-67 expression and prognosis in colorectal carcinoma.MethodsLgr5 and Ki-67 expression were evaluated by immunohistochemistry in 192 colorectal carcinoma specimens. Selection of side population (SP) cells was performed by staining with Hoechest 33342, and Lgr5 expression in Colo205 SP cells was then detected by immunofluorescence.ResultsLgr5 expression was significantly higher in carcinoma than in normal mucosa (P=0.001). Lgr5 was positively correlated with histological grade (P=0.001), depth of invasion (P=0.001), lymph node metastasis (P=0.001), distant metastasis (P=0.004), pTNM stage (P=0.001), and Ki-67 (r=0.446, P=0.001). Multivariate analysis showed that the effect of Lgr5 on survival was independent of Ki-67 (P=0.037). In the in vitro study, Hoechst low-staining cells were counted in 7% of the Colo205 colon cancer cell line population, and Lgr5 expression was strikingly stronger in Hoechst low-staining cells than in high-staining cells (P=0.001).ConclusionsThese findings suggest that Lgr5 may play an important role in the progression and prognosis of colorectal carcinoma, and may be a potential new therapeutic target for the treatment of colorectal cancer patients. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).
In abdominal emergencies with suspected or confirmed COVID-19, the surgical practice and relevant evidence is still lacking. The present report summarizes our experience in the diagnosis and treatment of four patients with acute abdomen and suspected COVID-19, with the aim of providing practical information for global surgical colleagues.
RAG is as acceptable as LAG for obtaining safe complications and for performing radical gastrectomy.
BackgroundCirculating tumor DNA (ctDNA) has offered a minimally invasive approach for detection and measurement of gastric cancer (GC). However, its diagnostic and prognostic value in gastric cancer still remains unclear.ResultsA total of 16 studies comprising 1193 GC patients met our inclusion criteria. The pooled sensitivity and specificity were 0.62 (95% confidence intervals (CI) 0.59−0.65) and 0.95 (95% CI 0.93–0.96), respectively. The AUSROC (area under SROC) curve was 0.94 (95% CI 0.89–0.98). The results showed that the presence of certain ctDNA markers was associated with larger tumor size (OR: 0.26, 95% CI 0.11–0.61, p = 0.002), TNM stage (I + II/III + IV, OR: 0.11, 95% CI 0.07−0.17, p = 0.000), as well as H. pylori infection. (H.p negative/H.p positive, OR: 0.57, 95% CI 0.36–0.91, p = 0.018). Moreover, there was also a significant association between the presence of ctDNA and worse overall survival (HR 1.77, 95% CI 1.38−2.28, p < 0.001), as well as disease-free survival (HR 4.36, 95% CI 3.08−6.16, p < 0.001).Materials and MethodsPubmed, Embase, Cochrane Library and Web of Science databases were searched for relating literature published up until November 30, 2016. Diagnostic accuracy variables were pooled by the Meta-Disc software. Engauge Digitizer and Stata software were applied for prognostic data extraction and analysis.ConclusionsOur meta-analysis indicates the detection of certain ctDNA targets is significantly associated with poor prognosis of GC patients, with high specificity and relatively moderate sensitivity.
This meta-analysis indicated that MMP-2 overexpression might be a predictive factor for poor prognosis for gastric cancer.
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