Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy

Accurate immune molecular typing is pivotal for screening out patients with colon adenocarcinoma (COAD) who may benefit from immunotherapy and whose tumor microenvironment (TME) was needed for reprogramming to beneficial immune-mediated responses. However, little is known about the immune characteristic of COAD. Here, by calculating the enrichment score of immune characteristics in three online COAD datasets (TCGA-COAD, GSE39582, and GSE17538), we identified 17 prognostic-related immune characteristics that overlapped in at least two datasets. We determined that COADs could be stratified into three immune subtypes (IS1–IS3), based on consensus clustering of these 17 immune characteristics. Each of the three ISs was associated with distinct clinicopathological characteristics, genetic aberrations, tumor-infiltrating immune cell composition, immunophenotyping (immune “hot” and immune “cold”), and cytokine profiles, as well as different clinical outcomes and immunotherapy/therapeutic response. Patients with the IS1 tumor had high immune infiltration but immunosuppressive phenotype, IS3 tumor is an immune “hot” phenotype, whereas those with the IS2 tumor had an immune “cold” phenotype. We further verified the distinct immune phenotype of IS1 and IS3 by an in-house COAD cohort. We propose that the immune subtyping can be utilized to identify COAD patients who will be affected by the tumor immune microenvironment. Furthermore, the ISs may provide a guide for personalized cancer immunotherapy and for tumor prognosis

Probe-Compensated Microwave Holographic Imaging

本論文提出了結合探針補償之微波全像術，採用擁有稍高增益的探針天線進行平面掃描式近場成像。首先由探針天線發射入射場至待測之散射物，再由該探針接收因散射物造成散射場，利用平面上不同位置收集到的散射場資訊進行微波成像。選用高增益探針天線進行研究是因為它可以降低散射場過弱而不易量測的難度。為了讓成像品質更好，我們額外考慮了探針的輻射特性以及其環境，進而將它們補償。本研究結合探針天線補償以及微波成像，除了理論推導外，並以模擬和實驗驗證。 在模擬方面，採用FEKO電磁模擬軟體進行一系列成像示範，並探討空間取樣率對成像品質的影響。在實驗方面，我們架設了一套成像系統，選用操作在X波段的微帶天線當作探針進行量測。除了前述利用單天線進行量測的系統外，我們亦考慮更適合量測薄弱散射場的準單天線系統。A novel probe-compensated microwave holographic imaging method is proposed. Planar scanning by a directive probe antenna is adopted to reconstruct the images of unknown metallic or dielectric targets. Unknown targets are first illuminated by the probe antenna, and then the fields scattered from the targets are received by the probe. Directive or moderate-gain probe antennas are adopted since they are more sensitive to the scattered fields. To enhance the image quality, the proposed approach necessitates the detailed radiation information of the probe antenna and its environment. Theoretical formulation for image reconstruction is derived and verified by both simulations and experiments. A series of imaging results based on FEKO simulations is presented to verify the efficacy of the proposed imaging approach. The effects of sampling rate on the image reconstruction are also investigated. Moreover, the experimental imaging system is also built up. A microstrip patch antenna that operates at X-band is chosen as the moderate-gain probe antenna. In addition to the monostatic imaging system, a quasi-monostatic system is also demonstrated. The quasi-monostatic system is more feasible and is capable of measuring the relatively weak fields scattered from dielectric targets.致謝 i 中文摘要 ii ABSTRACT iii CONTENT iv LIST OF FIGURES vi LIST OF TABLES x Chapter 1 Introduction 1 1.1 Research Background 1 1.2 Motivation and Methodology 2 1.3 Chapter Outline 3 Chapter 2 Probe-Compensated Holographic Imaging 4 2.1 Introduction 4 2.2 Response of a Receiving Antenna with an Exterior Source 5 2.3 Planar Scanning with Arbitrary Probe Antennas 8 2.4 Discussions on the Image Reconstruction Equation 12 2.4.1 Metallic Scatterers 12 2.4.2 Probe-Compensation Mechanisms 13 2.4.3 Comparison with the Uncompensated Approach 15 Chapter 3 Simulation Results and Parameter Survey 17 3.1 The Simulation Tool 17 3.2 Simulation Results with Probe-Compensated Technique 18 3.2.1 Using a Patch Antenna as the Probe 18 3.2.2 Using a Half-Wavelength Dipole Antenna as the Probe 23 3.2.3 Metallic Scatterers 28 3.3 Discussions on the Scanning Configuration 32 3.3.1 Comparison of a Patch Antenna and a Half-wavelength Dipole Antenna 32 3.3.2 Sampling Rate 34 Chapter 4 Holographic Imaging Systems and Measurement Results 39 4.1 Holographic Imaging Systems 39 4.1.1 System Descriptions 39 4.1.2 Probe Antennas 42 4.1.3 Scanning Setups 45 4.2 Image Results 47 4.2.1 The Monostatic System 47 4.2.2 The Quasi-monostatic System 51 Chapter 5 Conclusions 54 5.1 Summary 54 5.2 Future Work 55 Reference 5

Study on the Thermomechanical Response of Deep Buried Pipe Energy Piles under Temperature Load

A deep buried pipe energy pile (DBP-EP) is a composite structure that integrates ground-source heat pump (GSHP) systems and inside buried pipe energy piles (IBP-EP) to effectively achieve the improvement of heat transfer efficiency and quantity. Utilizing this technology in building a pile foundation can contribute to reducing carbon emissions. This paper studies the variation rules of the thermomechanical response of DBP-EP under temperature load via field testing and numerical simulation. The results show that, under heating and cooling conditions, the DBP-EP temperature variation within the pile is substantial, while there is no significant change in the temperature field at the bottom of the pile. This is different from the internal temperature change of the temperature distribution of IBP-EP. The minimum axial average strain of the DBP-EP under the cooling condition is significantly smaller than that under the heating condition. However, the additional axial average strain under the temperature load is significantly larger than that in the heating condition, resulting in larger additional axial stress when the pile is cooled. The connection between the pile and foundation must considered in design due to the large settlement of the pile top under cooling conditions. When only under the temperature load, the maximum axial average pressure increments of the pile in our test during heating and cooling are −85.3 kN/°C and 99.4 kN/°C, respectively, suggesting that the additional load cannot be ignored

Decreased mean platelet volume predicts poor prognosis in metastatic colorectal cancer patients treated with first-line chemotherapy: results from mCRC biomarker study

Abstract Background Metastatic colorectal cancer (mCRC) is a major cause of death of malignant tumor and the valuable prognostic biomarker for chemotherapy is crucial in decreasing mortality. Previous studies have proved the prognostic value of the mean platelet volume (MPV) in survival of primary operable CRC patients. However, the prognostic impact of MPV in mCRC is still unclear. In this study, we aimed to clarify the prognostic role of MPV in mCRC undergoing standard first-line chemotherapy. Methods From January 2012 to December 2016, we conducted a retrospective clinical study included 264 mCRC patients (NCT03532711). All the enrolled patients received the standard oxaliplatin-based or irinotecan-based chemotherapy. The association between the baseline MPV and clinicopathological features were examined. Results Univariate analysis revealed that decreased MPV, the platelet counts (PLT), platelet-to-lymphocyte ratio (PLR) and the platelet crit (PCT) were significantly associated with inferior overall survival (OS) (p < 0.05). On multivariate analysis, elevated PLR was significant prognostic factors for OS, with hazard ratios of (HR:1.006, 95% CI:1.001–1.011, p = 0.01) while MPV was not, respectively (p < 0.05). Conclusions Our study demonstrated that the baseline MPV level may act as a predictive factor for survival in mCRC patients undergoing standard chemotherapy. Trial registration This study was retrospectively registered in date May the 20th 2018. The registration number (TRN) of this study was NCT03532711

Prognostic Value of FGFR Gene Amplification in Patients with Different Types of Cancer: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Fibroblast growth factor receptor (FGFR) gene amplification has been reported in different types of cancer. We performed an up-to-date meta-analysis to further characterize the prognostic value of FGFR gene amplification in patients with cancer.</p><p>Methods</p><p>A search of several databases, including MEDLINE (PubMed), EMBASE, Web of Science, and China National Knowledge Infrastructure, was conducted to identify studies examining the association between FGFR gene amplification and cancer. A total of 24 studies met the inclusion criteria, and overall incidence rates, hazard risk (HR), overall survival, disease-free survival, and 95% confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included studies.</p><p>Results</p><p>In the meta-analysis of 24 studies, the prevalence of FGFR gene amplification was <i>FGFR1</i>: 0.11 (95% CI: 0.08–0.13) and <i>FGFR2</i>: 0.04 (95% CI: 0.02–0.06). Overall survival was significantly worse among patients with FGFR gene amplification: <i>FGFR1</i> [HR 1.57 (95% CI: 1.23–1.99); <i>p</i> = 0.0002] and <i>FGFR2</i> [HR 2.27 (95% CI: 1.73–3.00); <i>p</i><0.00001].</p><p>Conclusions</p><p>Current evidence supports the conclusion that the outcomes of patients with FGFR gene amplified cancers is worse than for those with non-FGFR gene amplified cancers.</p></div

Forest plots of studies evaluating HR of overall survival, comparing high <i>FGFR</i> amplification and non-amplification.

<p>(A) Analysis of <i>FGFR1</i> amplification and overall survival in various cancers. (B) Analysis of <i>FGFR2</i> amplification and overall survival in gastric cancer. The horizontal lines represent 95% CIs for estimating HR of FGFR gene amplification versus non-amplification. (▪) Overall estimates of the effects. CI, confidence interval; HR, hazard ratio; IV, XXX; SE, standard error.</p

Funnel plots of the association between <i>FGFR</i> amplification and overall survival.

<p>(A) Publication bias for <i>FGFR1</i> amplification and overall survival in various cancers. (B) Publication bias for <i>FGFR2</i> amplification and overall survival in gastric cancer. Each point represents a separate study. Log [Hazard Ratio], natural logarithm of HR; SE, standard error.</p

Forest plots describing the prevalence of <i>FGFR</i> amplification.

<p>(A) Analysis of the prevalence of <i>FGFR1</i> amplification. (B) Analysis of the prevalence of <i>FGFR2</i> amplification. The horizontal lines represent 95% CIs for estimating prevalence of FGFR gene amplification.(▪) Overall estimates of the effects.CI, confidence interval; ES, estimation.</p