Diabetic patients have a higher risk factor for colorectal cancer (CRC) metastasis. Stearoyl-CoA desaturase 1 (SCD1), the main enzyme responsible for producing monounsaturated fatty acids(MUFA) from ...saturated fatty acids, is frequently deregulated in both diabetes and CRC. The function and mechanism of SCD1 in metastasis of CRC and its relevance to glucose remains largely unknown.
SCD1 expression levels were analyzed in human CRC tissues and the Cancer Browser database ( https://genome-cancer.ucsc.edu/ ). CRC cell lines stably transfected with SCD1 shRNAs or vector were established to investigate the role of SCD1 in modulating migration and invasion of CRC cells. A glucose concentration gradient was set to investigate regulation of SCD1 in CRC relevant to diabetic conditions.
The clinical data analysis showed high expression of SCD1 in CRC tissues with a negative correlation with the prognosis of CRC. In vitro experiments revealed that SCD1 increased CRC progression through promoting epithelial-mesenchymal transition (EMT). Lipidomic analysis demonstrated that SCD1 increased MUFA levels and MUFA administration could rescue migration and invasion defect of CRC cells induced by SCD1 knockdown. Furthermore, SCD1-mediated progression of CRC was promoted by carbohydrate response-element binding protein (ChREBP) in response to high glucose. Mechanistically, hyperglycemia-SCD1-MUFA induced CRC cell migration and invasion by regulating PTEN.
Our findings show that SCD1 promotes metastasis of CRC cells through MUFA production and suppressing PTEN in response to glucose, which may be a novel mechanism for diabetes-induced CRC metastasis.
USP11 is an ubiquitin-specific protease that plays an important role in tumor progression via different mechanisms. However, the expression and prognostic significance of USP11 in colorectal cancer ...(CRC) remain unknown.
Bioinformatics analyses, qRT-PCR, western blotting, and immunohistochemistry were applied for investigating USP11 expression in CRC tissues. Kaplan–Meier analysis with log-rank test was used for survival analyses. LC–MS/MS was performed for identifying potential protein interactions with USP11. In vitro and in vivo assays were used for exploring the function of USP11 during the progression of CRC.
USP11 was overexpressed in CRC tissues and functioned as an oncogene. Overexpression or knockdown of USP11 promoted or inhibited, respectively, the growth and metastasis of CRC cells in vitro and in vivo. Mechanically, USP11 stabilized PPP1CA by deubiquitinating and protecting it from proteasome-mediated degradation. Moreover, the USP11/PPP1CA complex promoted CRC progression by activating the ERK/MAPK signaling pathway.
USP11 promoted tumor growth and metastasis in CRC via the ERK/MAPK pathway by stabilizing PPP1CA, suggesting USP11 is a potential prognostic marker.
This work was supported by National Natural Science Foundation of China (NSFC81530044, NSFC81220108021, NSFC81802343), Technology Major Project of China Grants 2017ZX10203206, Shanghai Sailing Program (19YF1409600) and The project of Shanghai Jiaotong University (YG2017QN30).
ObjectiveThis study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy.MethodsInitially, 20 ...patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis.ResultsIn 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb–IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions.ConclusionPerioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients’ recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions.Trial registration numberNCT04297202.
Purpose
To build and validate a radiomics nomogram integrated with the radiomics signature and subjective CT characteristics to predict the Ki-67 expression level of gastrointestinal stromal tumors ...(GISTs). Moreover, the purpose was to compare the performance of pathological Ki-67 expression level with predicted Ki-67 expression level in estimating the prognosis of GISTs patients.
Methods
According to pathological results, patients were classified into high-Ki-67 labeling index group (Ki-67 LI ≥ 5%) and low-Ki-67 LI group (Ki-67 LI < 5%). Radiomics features extracted from contrast-enhanced CT(CECT) images were selected and classified to build a radiomics signature. A combined model was built by incorporating radiomics signature and determinant subjective CT characteristics using multivariate logistic regression analysis. The diagnostic performance of the radiomics signature, subjective CT model and combined model were explored by receiver operating characteristic (ROC) curve analysis and Delong test. The model with best diagnostic performance was then set up for the prediction nomogram. Recurrence-free survival (RFS) rates were compared utilizing Kaplan–Meier curve.
Results
The generated combined model yielded the best diagnostic performance with area under the curve (AUC) values of 0.738 95% confidence interval (CI): 0.669–0.807 and 0.772 (95% CI 0.683–0.860) in the training set and testing set respectively. The nomogram based on the combined model demonstrated good calibration in the training set and testing set (both
P
> 0.05). Patients of high-Ki-67 LI group predicted by our nomogram had a poorer RFS than patients of low–Ki-67 LI group (
P
< 0.0001).
Conclusion
This radiomics nomogram based on CECT had a satisfactory performance in predicting both the Ki-67 expression level and prognosis noninvasively in patients with GISTs, which may serve as an effective imaging tool that can assist in guiding personalized clinical treatment.
Climate change (CC) and land use/cover change (LUCC) are the main drivers of streamflow change. In this study, the effects of CC and LUCC on streamflow regime as well as their spatial variability ...were examined by using the Distributed Hydrology Soil Vegetation Model (DHSVM) for the Beichuan River Basin in the northeast Tibetan Plateau. The results showed that CC increased annual and maximum streamflow in the upstream but decreased them in the downstream. CC also enhanced minimum streamflow in the whole river basin and advanced the occurrence of daily minimum streamflow. Temperature change exerted greater influence on streamflow regime than wind speed change did in most situations, but the impact of wind speed on streamflow reflected the characteristics of accumulative effects, which may require more attention in future, especially in large river basins. As for LUCC, cropland expansion and reservoir operation were the primary reasons for streamflow reduction. Cropland expansion contributed more to annual mean streamflow change, whereas reservoir operation greatly altered monthly streamflow pattern and extreme streamflow. Reservoir regulation also postponed the timing of minimum streamflow and extended durations of average, high, and low streamflow. Spatially, CC and LUCC played predominant roles in the upstream and the downstream, respectively.
Variations in vegetation are closely related to climate change, but understanding of their characteristics and causes remains limited. As a typical semi-humid and semi-arid cold plateau region, it is ...important to understand the knowledge of long term Normalized Difference Vegetation Index (NDVI) variations and find the potential causes in the source region of the Yangtze River. Based on four tree-ring width chronologies, the regional mean NDVI for July and August spanning the period 1665–2013 was reconstructed using a regression model, and it explained 43.9% of the total variance during the period 1981–2013. In decadal, the reconstructed NDVI showed eight growth stages (1754–1764, 1766–1783, 1794–1811, 1828–1838, 1843–1855, 1862–1873, 1897–1909, and 1932–1945) and four degradation stages (1679–1698, 1726–1753, 1910–1923, and 1988–2000). And based on wavelet analysis, significant cycles of 2–3 yr and 3–8 yr were identified. In additional, there was a significant positive correlation between the NDVI and the Palmer Drought Severity Index (PDSI) during the past 349 yr, and they were mainly in phase. However, according to the results of correlation analysis between different grades of drought/wet and NDVI, there was significant asymmetry in extreme drought years and extreme wet years. In extreme drought years, NDVI was positively correlated with PDSI, and in extreme wet years they were negatively correlated.
Adjuvant chemotherapy is considered the standard of care for patients with colorectal cancer after curative resection. Although current guidelines provide clear instructions for chemotherapy for ...stage II high-risk and stage III colorectal cancer, it is insufficient to individualize therapy. We analyzed the outcomes of 902 patients with colorectal cancer treated with or without chemotherapy in our hospital. We found Chinese survival benefit for chemotherapy was consistent with current guidelines. Moreover, our data added to the evidence that chemotherapy might be used for elderly patients with stage II high-risk colorectal cancer. Pathological markers could predict response to individualize therapy in a convenient, fast and inexpensive way. We compared survivals of patients with stage II high-risk and stage III colorectal cancer with chemotherapy in different pathological markers expression, and furthermore used 458 colon adenocarcinoma samples from The Cancer Genome Atlas to verify our preliminary results. We confirmed TOPIIα, EGFR and P170 may be sufficiently predictive markers to individualize chemotherapy. FOLFOX was the optimal adjuvant chemotherapy for patients with stage II high-risk and stage III colorectal cancer when TOPIIα was positive or EGFR or P170 was negative.
This is the first comprehensive evaluation of the Moderate Resolution Imaging Spectroradiometer (MODIS)-derived near-surface air temperature, which has been used widely in a series of large-scale ...models varying in various disciplines ranging from climatology, hydrology to ecology. Four retrieval methods: the highest available pressure in the atmospheric profile product, interpolation by the adiabatic lapse rate, interpolation by the hypsometric equation and the combination with land surface temperature, were developed in the past, but only with validation in regional scale. All of these are evaluated in this paper against 2168 hourly meteorological recordings with an elevation span of over 5000 m in China. Results show that the method of the highest available pressure exhibits a serious underestimation, especially in areas of high elevation, such as the Tibetan Plateau. Interpolation by the hypsometric equation can only fix the underestimation to a very small extent, while interpolation by the adiabatic lapse rate can achieve a relatively good performance. In addition to the elevation influence, substantially variable estimates occur with the parabola-like distribution in low elevation areas, which implies the influence of cloud in Southern China. The combination of the underestimation from interpolation by the adiabatic lapse rate and overestimation in land surface temperature can eliminate the disturbance of both elevation and cloud, resulting in the best performance with r = 0.94, bias = −0.83°C and root-mean-square-error = 4.18°C.
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•MODIS-derived near-surface air temperature using four methods are compared in China.•Elevation and clouds have significant impact on the performance of different methods.•Hydrostatic interpolation can solve the underestimation issue in high elevation area.•Averaging with land surface temperature reduces the elevation and cloud effects.•This study will provide important references for future use in global models.
Background
Radiomics‐based analyses have demonstrated impact on studies of endometrial cancer (EC). However, there have been no radiomics studies investigating preoperative assessment of ...MRI‐invisible EC to date.
Purpose
To develop and validate radiomics models based on sagittal T2‐weighted images (T2WI) and T1‐weighted contrast‐enhanced images (T1CE) for the preoperative assessment of MRI‐invisible early‐stage EC and myometrial invasion (MI).
Study Type
Retrospective.
Population
One hundred fifty‐eight consecutive patients (mean age 50.7 years) with MRI‐invisible endometrial lesions were enrolled from June 2016 to March 2022 and randomly divided into the training (n = 110) and validation cohort (n = 48) using a ratio of 7:3.
Field Strength/Sequence
3‐T, T2WI, and T1CE sequences, turbo spin echo.
Assessment
Two radiologists performed image segmentation and extracted features. Endometrial lesions were histopathologically classified as benign, dysplasia, and EC with or without MI. In the training cohort, 28 and 20 radiomics features were selected to build Model 1 and Model 2, respectively, generating rad‐score 1 (RS1) and rad‐score 2 (RS2) for evaluating MRI‐invisible EC and MI.
Statistical Tests
The least absolute shrinkage and selection operator logistic regression method was used to select radiomics features. Mann–Whitney U tests and Chi‐square test were used to analyze continuous and categorical variables. Receiver operating characteristic curve (ROC) and decision curve analysis were used for performance evaluation. The area under the ROC curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. A P‐value <0.05 was considered statistically significant.
Results
Model 1 had good performance for preoperative detecting of MRI‐invisible early‐stage EC in the training and validation cohorts (AUC: 0.873 and 0.918). In addition, Model 2 had good performance in assessment of MI of MRI‐invisible endometrial lesions in the training and validation cohorts (AUC: 0.854 and 0.834).
Data Conclusion
MRI‐based radiomics models may provide good performance for detecting MRI‐invisible EC and MI.
Evidence Level
3
Technical Efficacy
Stage 2
•ATF6 regulates interleukin-1α expression in macrophage.•Macrophage-derived interleukin-1α activates HSC.•ATF6 signal is involved in promoting liver fibrogenesis.
Macrophages contribute to liver ...fibrogenesis by the production of a large variety of cytokines. ATF6 is associated with the activation of macrophages. The present study aimed to investigate the role of ATF6 in the expression of macrophage-derived cytokines and liver fibrogenesis after acute liver injury. Following thioacetamide (TAA)-induced acute liver injury, the characteristics of the occurrence of liver fibrosis and the secretion of cytokines by macrophages were first described. Then, the role of various cytokines secreted by macrophages in activating hepatic stellate cells (HSCs) was tested in vitro. Finally, endoplasmic reticulum stress (ER-stress) signals in macrophages were detected following liver injury. siRNA was used to interfere with the expression of ATF6 in macrophages to verify the influence of ATF6 on cytokine expression and liver fibrogenesis after liver injury. A single intraperitoneal injection of TAA induced acute liver injury. The depletion of macrophages attenuated acute liver injury, while it inhibited liver fibrogenesis. During acute liver injury, macrophages secrete a variety of cytokines. Most of these cytokines promoted the activation of HSCs, but the effect of IL-1α was most significant. In the early stage of acute liver injury, ER-stress signals in macrophages were activated. Interference of ATF6 expression suppressed the secretion of cytokines by macrophages and attenuated liver fibrogenesis. Overall, in the early stage of acute liver injury, ATF6 signals promoted the expression of macrophage-derived cytokines to participate in liver fibrogenesis, and IL-1α exhibited the most significant role in promoting the activation of HSCs and liver fibrogenesis.
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