Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA.

Hepatocellular carcinoma (HCC) is a malignant tumor with high recurrence and metastasis rates and poor prognosis. Basement membrane is a ubiquitous extracellular matrix and is a key physical factor in cancer metastasis. Therefore, basement membrane-related genes may be new targets for the diagnosis and treatment of HCC. We systematically analyzed the expression pattern and prognostic value of basement membrane-related genes in HCC using the TCGA-HCC dataset, and constructed a new BMRGI based on WGCNA and machine learning. We used the HCC single-cell RNA-sequencing data in GSE146115 to describe the single-cell map of HCC, analyzed the interaction between different cell types, and explored the expression of model genes in different cell types. BMRGI can accurately predict the prognosis of HCC patients and was validated in the ICGC cohort. In addition, we also explored the underlying molecular mechanisms and tumor immune infiltration in different BMRGI subgroups, and confirmed the differences in response to immunotherapy in different BMRGI subgroups based on the TIDE algorithm. Then, we assessed the sensitivity of HCC patients to common drugs. In conclusion, our study provides a theoretical basis for the selection of immunotherapy and sensitive drugs in HCC patients. Finally, we also considered CTSA as the most critical basement membrane-related gene affecting HCC progression. In vitro experiments showed that the proliferation, migration and invasion abilities of HCC cells were significantly impaired when CTSA was knocked down.

Hsa_circ_0014784-induced YAP1 promoted the progression of pancreatic cancer by sponging miR-214-3p.

BACKGROUND: Pancreatic cancer (PC) is one of the most common gastrointestinal tumors globally. Former investigations discovered that circular RNAs (circRNAs) play an important role in PC development. circRNAs belong to a new class of endogenous noncoding RNAs, which have been found to mediate the progression of diverse types of tumors. Nevertheless, the roles of circRNAs and the underlying regulatory mechanisms in PC remain unknown. METHODS: In this study, our team employed next-generation sequencing (NGS) to examine the abnormal circRNA expression in PC tissues. The circRNA expression in PC cell lines and tissues was detected. Then, regulatory mechanism and targets were examined with bioinformatics analysis, luciferase reporting analysis, Transwell migration, 5-ethynyl-2'-deoxyuridine, and CCK-8 analysis. An in vivo experiment was employed to elucidate hsa_circ_0014784 roles in PC tumor growth and metastasis. RESULTS: The results showcased abnormal circRNA expression in PC tissues. Our lab also found that hsa_circ_0014784 expression incremented in PC tissues and cell lines, implying that hsa_circ_0014784 functioned in PC progression. hsa_circ_0014784 downregulation inhibited PC proliferation and invasion in vivo and in vitro. The bioinformatics and luciferase report data validated that both miR-214-3p and YAP1 were hsa_circ_0014784 binding partners. The overexpression of YAP1 reversed the migration, proliferation, and epithelial - mesenchymal transition (EMT) of PC cells and the angiogenic differentiation of HUVECs after miR-214-3p overexpression. CONCLUSION: Taken together, our study found that hsa_circ_0014784 downregulation decremented invasion, proliferation, EMT, and angiogenesis of PC by regulating miR-214-3p/YAP1 signaling.

Construction and validation of a metabolic-associated lncRNA risk index for predicting colorectal cancer prognosis.

Background: Metabolic reprogramming is one of the most important events in the development of tumors. Similarly, long non-coding RNAs are closely related to the occurrence and development of colorectal cancer (CRC). However, there is still a lack of systematic research on metabolism-related lncRNA in CRC. Methods: Expression data of metabolism-related genes and lncRNA were obtained from The Cancer Genome Atlas (TCGA). Hub metabolism-related genes (HMRG) were screened out by differential analysis and univariate Cox analysis; a metabolism-related lncRNA risk index (MRLncRI) was constructed by co-expression analysis, univariate Cox regression analysis, LASSO, and multivariate Cox regression analysis. Survival curves were drawn by the Kaplan-Meier method. The ssGSEA method assessed the tumor microenvironment of the sample, and the IPS assessed the patient's response to immunotherapy. "Oncopredict" assessed patient sensitivity to six common drugs. Results: MRLncRI has excellent predictive ability for CRC prognosis. Based on this, we also constructed a nomogram that is more suitable for clinical applications. Most immune cells and immune-related terms were higher in the high-risk group. IPS scores were higher in the high-risk group. In addition, the high-risk and low-risk groups were sensitive to different drugs. Conclusion: MRLncRI can accurately predict the prognosis of CRC patients, is a promising biomarker, and has guiding significance for the clinical treatment of CRC.

Real-time indocyanine green lymphangiography in radical resection of right colon cancer allows the identification of chyle leakage.

Chyle leakage can be caused by abdominal surgery and managed successfully without surgical treatment; however, no preventive measures are available. Therefore, we introduce a new method to prevent post-operative chyle leakage. To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of chyle fistula formation after radical resection of right colon cancer. Five patients with a diagnosis of right colon cancer undergoing laparoscopic radical colectomy with D3 lymph node dissection were examined in this study. At the end of the operation, two points of 2.5 mg ICG were injected subserosally at the proximal end of the anastomosis (1 ml per point). Then the surgical field was screened by using ICG fluorescence to accurately locate the chyle leakage. Chyle leakage was noted and repaired with a Hem-O-Lock. The volume of output of each drain after surgery was measured daily until the patients were discharged. We were able to observe ICG fluorescence in the lymphatic vessels within 3 minutes of ICG injection. This visualization allowed us to accurately locate and quickly repair chyle leakage within 5 minutes. Clinical observation after surgery and at a 1-month follow-up showed no chyle leakage in all 5 patients. Indocyanine green lymphangiography can feasibly guide the location and repair of chyle leakage after right colon cancer resection.

LyP-1-fMWNTs enhanced targeted delivery of MBD1siRNA to pancreatic cancer cells.

Functionalized multi-walled carbon nanotubes have been extensively gained popularity in pancreatic cancer gene therapy. LyP-1, a peptide, has been proved to specifically bind pancreatic cancer cells. The potential therapeutic effect of LyP-1-conjugated functionalized multi-walled carbon nanotubes in treating pancreatic cancer is still unknown. In this study, LyP-1-conjugated functionalized multi-walled carbon nanotubes were successfully synthesized, characterized and showed satisfactory size distribution and zeta potential. Compared with functionalized multi-walled carbon nanotubes, cellular uptake of LyP-1-functionalized multi-walled carbon nanotubes was shown to be increased. Compound of LyP-1-functionalized multi-walled carbon nanotubes and MBD1siRNA showed superior gene transfection efficiency. Moreover, LyP-1-fMWNTs/MBD1siRNA complex could significantly decrease the viability and proliferation and promoted apoptosis of pancreatic cancer cells in vitro. Further xenograft assays revealed that the tumour burden in the nude mice injected with LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA was significantly relieved. The study demonstrated that LyP-1-functionalized multi-walled carbon nanotubes/MBD1siRNA could be a promising candidate for tumour active targeting therapy in pancreatic cancer.

The roles of ID-1 in human pancreatic ductal adenocarcinoma and the therapeutic effects of 2-methoxyestradiol.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rate. Inhibitor of differentiation-1 (ID-1) overexpression has already been reported to be associated with low survival, but the detailed roles of ID-1 in PDAC are unclear. As an ID-1 inhibitor, 2-methoxyestradiol (2-ME) has been shown effective in the antitumor therapies, but its effect on PDAC is unknown. In this study, ID-1 overexpression and knockdown stable SW1990 cells were used to examine proliferation, migration and invasion abilities. Effectiveness of 2-ME was estimated in vivo, as well as in vitro by survival analysis, magnetic resonance imaging and tissue analysis. PDAC patients were retrospectively reviewed to assess the ID-1 expression and prognosis. We found that ID-1 was closely associated with in vitro SW1990 cells proliferation, migration and invasion abilities, as well as the expression of HIF-1α, VEGF and MMP-9. 2-ME was shown to be effective on tumor suppression both in vivo and in vitro, perhaps mainly by ID-1 regulation. Moreover, the relevance between high ID-1 expression and poor prognosis was validated in PDAC patients. Our data collectively reveals the roles of ID-1 in PDAC malignancy, and suggests 2-ME treatment may be a potential alternative chemotherapeutic agent for PDAC patients.

Radical resection and enucleation in Chinese adolescents with pancreatic tumors: A 15-year case series.

Pancreatic tumors rarely occur in adolescents, and the appropriateness of radical resection for these patients remains controversial.Medical records were retrospectively reviewed for patients younger than 19 years who underwent radical resection or limited resection (enucleation) between 2000 and 2015. Patient demographics, clinical characteristics, operative details, growth, and survival were analyzed.During the study period, 11 adolescents (mean age, 16.18 years; standard deviation, 1.99; interquartile range, 15.0-18.0) underwent radical resection (n = 7) or enucleation (n = 4) to treat solid pseudopapillary tumors (n = 5), pancreatic neuroendocrine tumors (n = 5), or pancreatic ductal adenocarcinoma (n = 1). None of the 7 patients who underwent radical resection experienced recurrence or serious complications, while 3 of 4 patients who underwent enucleation experienced recurrence (P = 0.02). Recurrence-free survival was slightly longer in patients who underwent radical resection, and this procedure did not appear to affect adolescent growth and development.Radical resection might be safe and effective for adolescents with pancreatic tumors.

Current status and progress of pancreatic cancer in China.

Cancer is currently one of the most important public health problems in the world. Pancreatic cancer is a fatal disease with poor prognosis. As in most other countries, the health burden of pancreatic cancer in China is increasing, with annual mortality rates almost equal to incidence rates. The increasing trend of pancreatic cancer incidence is more significant in the rural areas than in the urban areas. Annual diagnoses and deaths of pancreatic cancer in China are now beyond the number of cases in the United States. GLOBOCAN 2012 estimates that cases in China account for 19.45% (65727/337872) of all newly diagnosed pancreatic cancer and 19.27% (63662/330391) of all deaths from pancreatic cancer worldwide. The population's growing socioeconomic status contributes to the rapid increase of China's proportional contribution to global rates. Here, we present an overview of control programs for pancreatic cancer in China focusing on prevention, early diagnosis and treatment. In addition, we describe key epidemiological, demographic, and socioeconomic differences between China and developed countries. Facts including no nationwide screening program for pancreatic cancer, delay in early detection resulting in a late stage at presentation, lack of awareness of pancreatic cancer in the Chinese population, and low investment compared with other cancer types by government have led to backwardness in China's pancreatic cancer diagnosis and treatment. Finally, we suggest measures to improve health outcomes of pancreatic cancer patients in China.