Objective
To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma ...(MA)NEC.
Background
Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse.
Methods
A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG).
Results
The median follow-up time was 40 months (1–169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%,
p
< 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%).
Conclusions
Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing ...limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 muM and high sensitivity of 6829 muA mM.sup.- 1 cm.sup.- 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into ...the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and ...development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown.
Methods:
In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients.
Results:
The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4
+
memory T cells in gastric cancer.
In vitro
overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients.
Conclusion:
FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4
+
memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.
Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted growing attention as a noninvasive option for cancer treatment. At present, researchers have developed ...various "all-in-one" nanoplatforms for cancer imaging and PTT/PDT combinational therapy. However, the complex structure, tedious preparation procedures, overuse of extra carriers and severe side effects hinder their biomedical applications. In this work, we reported a nanoplatform (designated as ICG-MB) self-assembly from two different FDA-approved dyes of indocyanine green (ICG) and methylene blue (MB) without any additional excipients for cancer fluorescence imaging and combinational PTT/PDT. ICG-MB was found to exhibit good dispersion in the aqueous phase and improve the photostability and cellular uptake of free ICG and MB, thus exhibiting enhanced photothermal conversion and singlet oxygen (
O
) generation abilities to robustly ablate cancer cells under 808 nm and 670 nm laser irradiation. After intravenous injection, ICG-MB effectively accumulated at tumor sites with a near-infrared (NIR) fluorescence signal, which helped to delineate the targeted area for NIR laser-triggered phototoxicity. As a consequence, ICG-MB displayed a combinational PTT/PDT effect to potently inhibit tumor growth without causing any system toxicities in vivo. In conclusion, this minimalist, effective and biocompatible nanotheranostic would provide a promising candidate for cancer phototherapy based on current available dyes in clinic.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
To establish an early warning scoring system for septic shock in patients with digestive tract perforation (DTP) and evaluate its diagnostic efficacy.
Methods
Patients with surgically ...confirmed or clinically diagnosed DTP admitted to the Department of Intensive Care Medicine of Fujian Provincial Hospital from June 2012 to October 2021 were retrospectively analyzed. General demographic characteristics, perforation-related information, vital signs, common laboratory indicators, and common ICU scores (Glasgow Coma Scale score, Acute Physiology and Chronic Health Evaluation-II score,Sequential Organ Failure Assessment score) were collected. The patients were divided into shock group and non-shock group according to whether the patients had septic shock during hospitalization. The risk factors of septic shock were screened by basic statistical analysis and multivariate Logistic regression analysis. The receiver operating characteristic curve was drawn to determine the cut-off value of the continuous indicators and discretized with reference to clinic, and the corresponding score was set according to the β regression coefficient of each variable.
Results
A total of 176 patients with DTP were included. The average age of the patients was 64.13 ± 14.67 years old, and 74.40% were males. The incidence of septic shock was 30.11% (53/176). Multivariate Logistic regression analysis showed that the highest heart rate≥105 beats/min, Glasgow Coma Scale score≤14 points, lactic acid≥5.75 mmol/L, procalcitonin≥41.47 ug/L, C-reactive protein≥222.5 mg/L were independent risk factors for septic shock in patients with DTP. The total score of clinical diagnostic scoring system of septic shock in patients with DTP was 6 points, including the highest heart rate≥105 beats/min (1 point), lactic acid≥5.75 mmol/L (two points), procalcitonin≥41.47 ug/L (one point), C-reactive protein≥222.5 mg/L (1 point), and Glasgow Coma Scale score≤14 points (1 point). The area under ROC curve (AUC) of this scoring system was 0.789 and the 95% confidence interval was 0.717–0.860 (
P
< 0.001); when the optimal cut-off value was 2.5, the sensitivity and specificity were 54.70 and 87.80%, respectively.
Conclusion
This new score system has its certain clinical value and has important guiding significance for clinicians to judge the prognosis of patients with DTP in time.
We present a valid and reproducible nomogram that combined the TNM stage as well as the Ki-67 index and carcinoembryonic antigen levels; the nomogram may be an indispensable tool to help predict ...individualized risks of death and help clinicians manage patients with gastric neuroendocrine carcinoma.
To analyze the long-term outcomes of patients with grade 3 GNEC who underwent curative surgery and investigated whether the combination of carcinoembryonic antigen (CEA) levels and Ki-67 index can predict the prognosis of patients with gastric neuroendocrine carcinoma (GNEC) and constructed a nomogram to predict patient survival.
In the training cohort, data were collected from 405 patients with GNEC after radical surgery at seven Chinese centers. A nomogram was constructed to predict long-term prognosis. Data for the validation cohort were collected from 305 patients.
The 5-year overall survival (OS) was worse in the high CEA group than in the normal CEA group (40.5% vs. 55.2%, p = 0.013). The 5-year OS was significantly worse in the high Ki-67 index group than in the low Ki-67 index group (47.9% vs. 57.2%, p = 0.012). Accordingly, we divided the whole cohort into a KC(-) group (low Ki-67 index and normal CEA) and KC(+) group (high Ki-67 index and/or high CEA). The KC(+) group had a worse prognosis than the KC(-) group (64.6% vs. 46.8%, p < 0.001). KC(+) and the AJCC 8
stage were independent factors for OS. Then, we combined KC status and the AJCC 8
stage to establish a nomogram; the C-index and area under the curve (AUC) were higher for the nomogram than for the AJCC 8
stage (C-index: 0.660 vs. 0.635, p = 0.005; AUC: 0.700 vs. 0.675, p = 0.020). The calibration curve verified that the nomogram had a good predictive value, with similar findings in the validation groups.
The nomogram based on KC status and the AJCC 8
stage predicted the prognosis of patients with GNEC well.
Glioblastoma (GBM) is the most common glial tumour and has extremely poor prognosis. GBM stem-like cells drive tumorigenesis and progression. However, a systematic assessment of stemness indices and ...their association with immunological properties in GBM is lacking. We collected 874 GBM samples from four GBM cohorts (TCGA, CGGA, GSE4412, and GSE13041) and calculated the mRNA expression-based stemness indices (mRNAsi) and corrected mRNAsi (c_mRNAsi, mRNAsi/tumour purity) with OCLR algorithm. Then, mRNAsi/c_mRNAsi were used to quantify the stemness traits that correlated significantly with prognosis. Additionally, confounding variables were identified. We used discrimination, calibration, and model improvement capability to evaluate the established models. Finally, the
algorithm and ssGSEA were implemented for functional analysis. Patients with high mRNAsi/c_mRNAsi GBM showed better prognosis among the four GBM cohorts. After identifying the confounding variables, c_mRNAsi still maintained its prognostic value. Model evaluation showed that the c_mRNAsi-based model performed well. Patients with high c_mRNAsi exhibited significant immune suppression. Moreover, c_mRNAsi correlated negatively with infiltrating levels of immune-related cells. In addition, ssGSEA revealed that immune-related pathways were generally activated in patients with high c_mRNAsi. We comprehensively evaluated GBM stemness indices based on large cohorts and established a c_mRNAsi-based classifier for prognosis prediction.
Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous ...composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC.
HER2
amplification and
TP53
and
APC
mutation rates were lower, whereas
SMAD4
,
PIK3CA
,
ACVR2A
,
KMT2D
,
LRP1
,
TGFBR2
,
GRIN2A
,
BRAF
V600E,
PTEN
, and
BRCA2
mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF-β pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.
Functional photothermal nanomaterials have gained widespread attention in the field of precise cancer therapy and early disease diagnosis due to their unique photothermal conversion properties. ...However, the relatively narrow temperature response range and the outputable accuracy of commercial thermometers limit the accurate detection of biomarkers. Herein, we designed a liposome-embedded Cu2–xAgxS amplification-based photothermal sensor for the accurate determination of cardiac troponin I (cTnI) in health monitoring and point-of-care testing (POCT). The combinable 3D-printing detecting device monitored and visualized target signal changes in the testing system under the excitation of near-infrared (NIR) light, which was recorded and evaluated for possible pathogenicity by a smartphone. Notably, we predicted the potentially efficient thermal conversion efficiency of Cu2–xAgxS from the structure and charge density distribution, calculated by the first-principles and density functional theory (DFT), which provided a theoretical basis for the construction of novel photothermal materials, and the experimental results proved the correctness of the theoretical projections. Under optimal conditions, the photothermal immunoassay showed a dynamic linear range of 0.02–10 ng mL–1 with a detection limit of 11.2 pg mL–1. This work instructively introduces promising theoretical research and provides new insights for the development of sensitive portable photothermal biosensors.
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IJS, KILJ, NUK, PNG, UL, UM
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