Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Multimodal data integration for predicting progression risk in castration-resistant prostate cancer using deep learning: a multicenter retrospective study.

Purpose: Patients with advanced prostate cancer (PCa) often develop castration-resistant PCa (CRPC) with poor prognosis. Prognostic information obtained from multiparametric magnetic resonance imaging (mpMRI) and histopathology specimens can be effectively utilized through artificial intelligence (AI) techniques. The objective of this study is to construct an AI-based CRPC progress prediction model by integrating multimodal data. Methods and materials: Data from 399 patients diagnosed with PCa at three medical centers between January 2018 and January 2021 were collected retrospectively. We delineated regions of interest (ROIs) from 3 MRI sequences viz, T2WI, DWI, and ADC and utilized a cropping tool to extract the largest section of each ROI. We selected representative pathological hematoxylin and eosin (H&E) slides for deep-learning model training. A joint combined model nomogram was constructed. ROC curves and calibration curves were plotted to assess the predictive performance and goodness of fit of the model. We generated decision curve analysis (DCA) curves and Kaplan-Meier (KM) survival curves to evaluate the clinical net benefit of the model and its association with progression-free survival (PFS). Results: The AUC of the machine learning (ML) model was 0.755. The best deep learning (DL) model for radiomics and pathomics was the ResNet-50 model, with an AUC of 0.768 and 0.752, respectively. The nomogram graph showed that DL model contributed the most, and the AUC for the combined model was 0.86. The calibration curves and DCA indicate that the combined model had a good calibration ability and net clinical benefit. The KM curve indicated that the model integrating multimodal data can guide patient prognosis and management strategies. Conclusion: The integration of multimodal data effectively improves the prediction of risk for the progression of PCa to CRPC.

Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment.

By the year 2035 more than 4 billion people might be affected by obesity and being overweight. Adipocyte-derived Extracellular Vesicles (ADEVs/ADEV-singular) are essential for communication between the tumor microenvironment (TME) and obesity, emerging as a prominent mechanism of tumor progression. Adipose tissue (AT) becomes hypertrophic and hyperplastic in an obese state resulting in insulin resistance in the body. This modifies the energy supply to tumor cells and simultaneously stimulates the production of pro-inflammatory adipokines. In addition, obese AT has a dysregulated cargo content of discharged ADEVs, leading to elevated amounts of pro-inflammatory proteins, fatty acids, and carcinogenic microRNAs. ADEVs are strongly associated with hallmarks of cancer (proliferation and resistance to cell death, angiogenesis, invasion, metastasis, immunological response) and may be useful as biomarkers and antitumor therapy strategy. Given the present developments in obesity and cancer-related research, we conclude by outlining significant challenges and significant advances that must be addressed expeditiously to promote ADEVs research and clinical applications.

Expression and Clinical Significance of PIEZO2 in Gastric Cancer.

OBJECTIVE: The aim of this research was to investigate the expression of PIEZO2 and its potential clinical significance in gastric cancer (GC). METHODS: In this study, we detected the protein expression levels of PIEZO2 in GC tissues and adjacent normal tissues by immunohistochemistry (IHC) and analysed the relationship between the protein expression levels of PIEZO2 and clinicopathological parameters of GC patients. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier Plotter were used to verify the diagnostic and prognostic values of PIEZO2. Proteins interacting with PIEZO2 were predicted using the SRING database. RESULTS: Our results showed that the protein expression levels of PIEZO2 in GC tissues were lower than those in adjacent normal tissues (all P < 0.05), and the protein expression level of PIEZO2 was correlated with lymph node metastasis and TNM stage of GC patients (all P < 0.05). Aberrant overexpression of PIEZO2 was associated with poor prognosis of GC patients. Proteins such as VR1, TRPV1, LHFPL5, STOM, TRPA1 and STOML3 had obvious interactions with PIEZO2 (P = 0.00213). CONCLUSION: In summary, our current study identified PIEZO2 as a promising target for early diagnosis and as a potential prognostic biomarker in GC patients.

Treatment of pyogenic liver abscess by surgical incision and drainage combined with platelet-rich plasma: A case report.

BACKGROUND: Pyogenic liver abscesses are insidious in the early stage. Some cases progress rapidly, and the patient's condition can worsen and even become life-threatening if timely treatment is not provided. Surgery and prolonged antibiotic treatment are often required if the abscess is large and liquefied and becomes separated within the lumen. CASE SUMMARY: We report a case of bacterial liver abscess with a poor outcome following pharmacological treatment, review the literature related to the use of platelet-rich plasma (PRP) in the treatment of hepatic impairment and partial hepatectomy in animals, and discuss the prognostic features of surgical incision and drainage combined with PRP in the treatment of bacterial liver abscesses. This is the first case describing the use of PRP in the treatment of a bacterial liver abscess in humans, providing new ideas for the treatment of this condition. CONCLUSION: This case highlights the importance of surgical treatment for bacterial liver abscesses that are well liquefied and poorly managed medically. PRP may produce antimicrobial effects and promote the regeneration and repair of liver tissue.

Distal pancreatectomy with En bloc celiac axis resection for locally advanced pancreatic body/tail cancer: A systematic review and meta-analysis.

Distal pancreatectomy with En-bloc celiac axis resection (DP-CAR) is a challenging procedure that has yielded certain clinical efficacy in the treatment of locally advanced pancreatic body/tail cancer, especially in patients with invasion of abdominal vessels. However, the clinical efficacy and safety of DP-CAR remain controversial. The study aimed to systematically review efficacy and safety of DP-CAR in the treatment of locally advanced pancreatic body/tail cancer. We systematically searched PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to 1 October 2020. Two studiers independently accomplished the study selection, data extraction, and quality assessment. Initially, of 1032 studies were searched, among which 11 high quality studies including 1072 patients were finally identified. The pooled results showed that DP-CAR versus Distal pancreatectomy (DP), the rate of R0 resection (RR = 0.76; 95%CI: 0.66 to 0.88; p = 0.0002) and 3-year survival (RR = 0.65; 95%CI: 0.43 to 0.98; p = 0.04) was lower, postoperative mortality (RR = 2.48; 95%CI: 1.02 to 6.03; p = 0.04) was higher, the operation time (MD = 104.67; 95%CI: 84.70 to 124.64; p < 0.001) and hospital stay (MD = 3.94, 95% CI 1.35 to 6.53; p = 0.003) were longer. There was no statistical difference between the DP-CAR and DP group in 1-year, 2-year survival rate (RR = 0.84; 95%CI: 0.57 to 1.23; p = 0.37) (RR = 0.70; 95%CI: 0.45 to 1.10; p = 0.12). In conclusion, compared with DP, DP-CAR has worse efficacy and prognosis survival and is more dangerous, but it can obtain better survival benefit and quality of life than palliative treatment. We suggest that DP-CAR can be carefully attempted for effective margin-negative resection. However, surgeons and patients need to know its potential perioperative risk.

[S-Adenosylmethionine Inhibits Expression of Vascular Endothelial Growth Factor-C Protein and Cellular Proliferation in Gastric Cancer].

OBJECTIVE: To explore inhibitory effects of S-adenosylmethionine on vascular endothelial growth factor-C (VEGF-C) protein and cellular proliferation in gastric cancer by regulating methylation status of VEGF-C promoter. METHODS: MTT analyses and nude mice model were employed to examine the effects of S- adenosylmethionine on inhibiting gastric cancer growth in vitro and in vivo. The protein expression of VEGF-C in gastric cancer cells was assessed by Western blot. The methylation status of VEGF-C promoter was assessed by bisulfite genomic DNA sequencing analysis. RESULTS: VEGF-C promoter was hypomethylated in MGC803 and SGC7901. The treatment of S-adenosylmethionine resulted in a heavy hypermethylation of VEGF-C promoter, which consequently down regulated protein level of VEGF-C. S-adenosylmethionine effectively inhibited the growth of gastric cancer cells in vitro and in vivo (P<0. 05). CONCLUSION: S-adenosylmethionine can effectively reverse DNA hypomethylation on VEGF-C promoter which down-regulates VEGF-C protein expression and inhibit gastric cancer growth.

Tumor lymphangiogenesis and lymphangiogenic growth factors.

Recent studies have revealed that malignant tumors can actively induce the formation of new lymphatic vessels and metastasize through the lymphatic system. Tumor-induced lymphangiogenesis driven by tumors expressed lymphangiogenic growth factors such as VEGF family, fibroblast growth factor 2 (FGF-2), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and platelet-derived growth factors (PDGFs) is correlated with lymph node metastasis in experimental cancer models and in several types of human cancers. Tumor- induced lymphangiogenesis has now been firmly established as a novel mechanism for cancer progression and lymph node metastasis. Recent studies indicate that blockade of the lymphangiogenic growth factors pathway inhibits tumor spread to lymph nodes and likely beyond. The potential effects of most of these newly identified lymphatic growth factors on tumor-induced lymphangiogenesis and lymph node metastasis remain to be further investigated. A number of questions remain to be answered concerning the potential efficacy of targeting at tumor-induced lymphangiogenesis for inhibiting tumor spread to lymph nodes.

Expression of cyclooxygenase-2 and vascular endothelial growth factor-C correlates with lymphangiogenesis and lymphatic invasion in human gastric cancer.

BACKGROUND: Recent observations have suggested that overexpression of cyclooxygenase-2 (COX-2) promotes tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C (VEGF-C) expression. It is unclear whether this mechanism also acts in gastric cancer. The aim of this study was to determine the relationship between COX-2 and VEGF-C expression in human gastric cancer, as well as to correlate with lymph node involvement, prognosis, and other clinicopathologic parameters. METHODS: Sixty-eight primary gastric cancers were immunohistochemically examined for COX-2, VEGF-C, vascular endothelial growth factor receptor-3 (VEGFR-3, also known as Flt-4), and CD34 expressions. Assessment of Flt-4-positive vessel density (FVD) and microvessel density (MVD) was performed. Then we analyzed their relationships and correlations with clinicopathologic findings and patients' survival time. RESULTS: The positivity rate of COX-2 and VEGF-C in the primary tumor was 67.7 and 54.4 percent, respectively. A significant correlation was found between the expression of VEGF-C and COX-2, and both were also correlated to MVD, FVD, lymphatic invasion, and TNM stage (p<0.05). COX-2 immunoreactivity was also associated with lymph node metastasis and serosa invasion. Increased MVD was significantly associated with lymph node metastasis and TNM stage. Both COX-2 and VEGF-C expression significantly correlated with poorer prognosis. CONCLUSIONS: Our data suggest that the expression of COX-2 correlates with VEGF-C expression and both of them correlate with the presence of lymphatic invasion and prognosis in gastric cancer. COX-2-mediated VEGF-C overexpression might promote lymphatic invasion via lymphangiogenesis pathway in patients with gastric cancer.

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation.

AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression. METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined. RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% (25/60), and 25.0% (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group of pT(4) (15/16 vs 9/16, P < 0.05), P(1-3) (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index (PI), (55.00 +/- 6.59 vs 27.43 +/- 7.72, 57.26 +/- 10.18 vs 29.15 +/- 8.31, and 49.82 +/- 6.74 vs 24.65 +/- 7.33, respectively, P < 0.05). CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

[Expression of galectin-3 mRNA in gastric cancer with peritoneal metastasis].

OBJECTIVE: To search for the role of galectin-3 gene in gastric cancer with peritoneal metastasis. METHODS: Using real-time quantitative RT-PCR for detecting the expression of galectin-3 mRNA in 35 matched samples, including primary cancer lesions, lymph node lesions, peritoneal metastasis and adjacent noncancerous mucosa. ANOVA and SNK-q test were used. RESULTS: The levels of mean expression of galectin-3 mRNA in gastric cancer (385.639 +/- 98. 534), in peritoneal metastasis (368.589 +/- 93.431) and in lymph node metastasis (375.920 +/- 94.346) were significantly higher than that in noncancerous mucosa (2.158 +/- 0.896); there were statistically significant differences respectively (P < 0.05). However, the levels of the expression in gastric cancer, in peritoneal metastasis and in lymph node metastasis were shown to be of no significant differences by multiple comparison, P > 0.05. The expression level in the group of gastric cancer was noted to have positive correlation with that in the group of peritoneal metastasis. These data indicated that the expression levels of galectin-3 in gastric cancer were well correlated to peritoneal metastasis. CONCLUSION: The overexpression of galectin-3 in gastric cancer is well correlated with peritoneal metastasis. Galectin-3 mRNA level may serve as a biological marker in the pre-operative judgment on whether the gastric cancer has had peritoneal metastasis or has just the potential of metastasis.

[Study on association between the expression of galectin- 3 and the peritoneal metastasis in gastric cancer].

OBJECTIVE: To investigate the association between the expression of galectin- 3 protein and peritoneal metastasis in gastric cancer. METHOD: The expressions of galectin- 3 was detected in matching- samples including primary gastric cancer lesions,lymph node metastases,peritoneal metastases and paratumor normal tissues by immunohistochemistry. All specimens were gained from 35 patients who had synchronous peritoneal metastasis from gastric cancer. RESULTS: The over- expression of galectin- 3 was observed in 97% (34/35) of the gastric cancer lesions, the peritoneal metastases and the lymph node metastases,whereas in 14% (5/35) of paratumor normal tissues. There were significant differences in the expression of galectin- 3 between paratumor normal tissues and the gastric carcinoma lesions,peritoneal metastases and lymph node metastases (P< 0.05),but there were no significant differences among the gastric cancer lesions,the peritoneal metastases,and the lymph node metastases (P> 0.05). CONCLUSION: The expression of galectin- 3 in gastric cancer lesions can be used as a biological marker of peritoneal metastasis from gastric cancer before operation and as a prognostic factor of gastric cancer.

[IGFBP-2 mRNA expression in gastric cancer tissues and its roles in proliferation, differentiation and peritoneal metastasis of gastric cancer].

OBJECTIVE: To detect the expression of IGFBP-2 mRNA in gastric cancer tissues and its roles in neoplasia and peritoneal metastasis of gastric cancer. METHODS: The IGFBP-2 mRNA expression levels in the fresh tissues from normal mucosa, primary cancer and peritoneal metastasis of 35 patients with gastric cancer were determined by the quantitative real time RT-PCR method, and the samples were sliced up and stained with hematoxylin-eosin for pathologyical examination. RESULTS: The levels of IGFBP-2 mRNA expression in gastric primary cancer tissues were significantly higher than those in the tissues from normal mucosa and peritoneal metastasis (P<0.05). Yet, IGFBP-2 mRNA expression levels showed no difference between the tissues of normal mucosa and peritoneal metastasis (P>0.05). CONCLUSION: The expression of IGFBP-2 mRNA possibly plays an important role in proliferation, differentiation and peritoneal metastasis of gastric cancer, and it might be useful in a new method for clinical prognostication and treatment of gastric cancer peritoneal metastasis.