A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.

YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2/ERα target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ERα cofactors in regulating cancer growth, highlighting the potential of YAP/TEAD as possible actionable drug targets for ERα+ breast cancer.

X-ray Activated Nanoprodrug for Visualization of Cortical Microvascular Alterations and NIR-II Image-Guided Chemo-Radiotherapy of Glioblastoma.

The permeability of the highly selective blood-brain barrier (BBB) to anticancer drugs and the difficulties in defining deep tumor boundaries often reduce the effectiveness of glioma treatment. Thus, exploring the combination of multiple treatment modalities under the guidance of second-generation near-infrared (NIR-II) window fluorescence (FL) imaging is considered a strategic approach in glioma theranostics. Herein, a hybrid X-ray-activated nanoprodrug was developed to precisely visualize the structural features of glioma microvasculature and delineate the boundary of glioma for synergistic chemo-radiotherapy. The nanoprodrug comprised down-converted nanoparticle (DCNP) coated with X-ray sensitive poly(Se-Se/DOX-co-acrylic acid) and targeted Angiopep-2 peptide (DCNP@P(Se-DOX)@ANG). Because of its ultrasmall size and the presence of DOX, the nanoprodrug could easily cross BBB to precisely monitor and localize glioblastoma via intracranial NIR-II FL imaging and synergistically administer antiglioblastoma chemo-radiotherapy through specific X-ray-induced DOX release and radiosensitization. This study provides a novel and effective strategy for glioblastoma imaging and chemo-radiotherapy.

Development and validation of an inflammatory biomarkers model to predict gastric cancer prognosis: a multi-center cohort study in China.

BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.

CLIC1-mediated autophagy confers resistance to DDP in gastric cancer.

Gastric cancer has been a constant concern to researchers as one of the most common malignant tumors worldwide. The treatment options for gastric cancer include surgery, chemotherapy and traditional Chinese medicine. Chemotherapy is an effective treatment for patients with advanced gastric cancer. Cisplatin (DDP) has been approved as a critical chemotherapy drug to treat various kinds of solid tumors. Although DDP is an effective chemotherapeutic agent, many patients develop drug resistance during treatment, which has become a severe problem in clinical chemotherapy. This study aims to investigate the mechanism of DDP resistance in gastric cancer. The results show that intracellular chloride channel 1 (CLIC1) expression was increased in AGS/DDP and MKN28/DDP, and as compared to the parental cells, autophagy was activated. In addition, the sensitivity of gastric cancer cells to DDP was decreased compared to the control group, and autophagy increased after overexpression of CLIC1. On the contrary, gastric cancer cells were more sensitive to cisplatin after transfection of CLIC1siRNA or treatment with autophagy inhibitors. These experiments suggest that CLIC1 could alter the sensitivity of gastric cancer cells to DDP by activating autophagy. Overall, the results of this study recommend a novel mechanism of DDP resistance in gastric cancer.

Prevalence and unfavorable outcome of frailty in older adults with gastric cancer: a systematic review and meta-analysis.

BACKGROUND AND AIM: Previous studies reported inconsistent results on the prevalence and prognostic implications of frailty among older adults with gastric cancer. This systematic review synthesized available literature pertaining on this topic to establish the prevalence and unfavorable outcomes of frailty in older adults with gastric cancer. METHODS: A comprehensive search was conducted across multiple English databases including PubMed, Cochrane Library, CINAHL, Embase, and Web of Science as well as Chinese databases, namely, CNKI, Wan Fang, and CBM, from inception to July 4, 2023, to identify potential studies. Data related to the incidence of frailty and its unfavorable outcomes in older adults with gastric cancer were extracted. RevMan5.3 and R 4.2.2 were used to evaluate pooled prevalence, hazard ratios (HR), and 95% confidence interval (CI). RESULTS: This review comprehensively selected 13 studies, comprising 9 cohort studies and 4 cross-sectional studies, on 44,117 older adults diagnosed with gastric cancer. The incidence of frailty among older adults with gastric cancer ranged from 10 to 71%. The pooled prevalence of frailty was 29% (95% CI 0.21-0.39). Frailty was found to be associated with an elevated risk of postoperative complications (HR = 1.99, 95% CI 1.45-2.73), prolonged postoperative hospital stay (HR = 2.68, 95% CI 2.38-3.02), likelihood of readmission (HR = 3.28, 95% CI 1.77-6.08), and an increased mortality risk (HR = 1.60, 95% CI 1.36-1.90). CONCLUSIONS: Frailty was associated with a poor prognosis in older adults with gastric cancer. Clinical medical staff should focus on the frailty of older adults with gastric cancer, conduct large-scale, multicenter, and prospective studies and early screening of patients, and provide guidance for the implementation of prevention and treatment strategies.

Investigating the prognostic and predictive value of the type II cystatin genes in gastric cancer.

BACKGROUND: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated. METHODS: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism. RESULTS: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS. CONCLUSIONS: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC.

The Prognostic Significance of Nomogram-Based Pretreatment Inflammatory Indicators in Patients With Esophageal Squamous Cell Carcinoma Receiving Intensity-Modulated Radiotherapy.

BACKGROUND: At present, there is no objective prognostic index available for patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiotherapy (IMRT). This study is to develop a nomogram based on hematologic inflammatory indices for ESCC patients treated with IMRT. METHODS: 581 patients with ESCC receiving definitive IMRT were enrolled in our retrospective study. Of which, 434 patients with treatment-naïve ESCC in Fujian Cancer Hospital were defined as the training cohort. Additional 147 newly diagnosed ESCC patients were used as the validation cohort. Independent predictors of overall survival (OS) were employed to establish a nomogram model. The predictive ability was evaluated by time-dependent receiver operating characteristic curves, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI). Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram model. The entire series was divided into 3 risk subgroups stratified by the total nomogram scores. RESULTS: Clinical TNM staging, primary gross tumor volume, chemotherapy, neutrophil-to-lymphocyte ratio and platelet lymphocyte ratio were independent predictors of OS. Nomogram was developed incorporating these factors. Compared with the 8th American Joint Committee on Cancer (AJCC) staging, the C-index for 5-year OS (.627 and .629) and the AUC value of 5-year OS (.706 and .719) in the training and validation cohorts (respectively) were superior. Furthermore, the nomogram model presented higher NRI and IDI. DCA also demonstrated that the nomogram model provided greater clinical benefit. Finally, patients with <84.8, 84.8-151.4, and >151.4 points were categorized into low-risk, intermediate-risk, and high-risk groups. Their 5-year OS rates were 44.0%, 23.6%, and 8.9%, respectively. The C-index was .625, which was higher than the 8th AJCC staging. CONCLUSIONS: We have developed a nomogram model that enables risk-stratification of patients with ESCC receiving definitive IMRT. Our findings may serve as a reference for personalized treatment.

Fine-Tuning Tridentate Ligands for the Construction of Nanotube-Based Boron Imidazolate Frameworks with High Chemical Stability.

Two unusual nanotube-based boron imidazolate frameworks (BIF-134 and BIF-135) were synthesized by a dual-ligand synthetic strategy under solvothermal conditions. In the structure of BIF-134 ([Co(BH(2-mim)3)(BTC)1/3](HBH(2-mim)3)1/3(NMA); 2-mim = 2-methylimidazole, NMA = N-methylacetamide, and BTC = 1,3,5-benzene tricarboxylate), one part of boron imidazolate ligands participate in the structural skeleton coordination, while another part of boron imidazolate ligands act as guest molecules that are located between adjacent nanotubes, which enhance the stability of the framework by the host-guest interaction and the pore space partition effects. It was found to be highly stable in air, water, organic solvents, and a wide pH range (pH 0-12). However, in the structure of BIF-135 ([Zn(BH(2-mim)3)(CHTC)1/3]; CHTC = 1,3,5-cyclohexanetricarboxylate), all boron imidazolate ligands participate in the structural skeleton coordination; there is no boron imidazolate guest molecule in the pores. The topology of BIF-135 is similar to that of BIF-134 by replacing BTC with CHTC and replacing Co with Zn. Furthermore, the obtained BIFs exhibited third-order nonlinear optical properties and potential optical limiting applications demonstrated by reverse saturable absorption.

Characteristics of transcription profile, adhesion and migration of SETD2-loss Met-5A mesothelial cells exposed with crocidolite.

Asbestos is a fibrous silicate mineral exhibiting biopersistence and carcinogenic properties and contributes to mesothelioma. Despite the concept of gene-environmental interaction in pathogenesis of mesothelioma, the possible pathophysiological changes of mesothelial cells simultaneously with SET domain containing 2 (SETD2) loss and asbestos exposure remains obscure. Herein, CRISPR/Cas9-mediated SETD2 knockout Met-5A mesothelial cells (Met-5ASETD2-KO ) were established and exposed with crocidolite, an amphibole asbestos. Cell viability of Met-5ASETD2-KO appeared to dramatically decrease with ≥2.5 µg/cm2 crocidolite exposure as compared with Met-5A, although no cytotoxicity and apoptosis changes of Met-5ASETD2-KO and Met-5A was evident with 1.25 µg/cm2 crocidolite exposure for 48 h. RNA sequencing uncovered top 50 differentially expressed genes (DEGs) between 1.25 µg/cm2 crocidolite exposed Met-5ASETD2-KO (Cro-Met-5ASETD2-KO ) and 1.25 µg/cm2 crocidolite exposed Met-5A (Cro-Met-5A), and ITGA4, THBS2, MYL7, RAC2, CADM1, and CLDN11 appeared to be the primary DEGs involved with adhesion in gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Cro-Met-5ASETD2-KO had strong migration but mild adhesion behavior as compared with Cro-Met-5A. Additionally, crocidolite tended to increase migration of Met-5ASETD2-KO but inhibited migration of Met-5A when compared with their corresponding cells without crocidolite exposure, although no further adhesion property changes was evident for both cells in response to crocidolite. Therefore, crocidolite may affect adhesion-related gene expression and modify adhesion and migration behavior for SETD2-depleted Met-5A, which could provide preliminary insight regarding the potential role of SETD2 in the cell behavior of asbestos-related malignant mesothelial cell.

SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway.

SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

Comparison of Two Major Staging Systems in Predicting Survival and Recommendation of Postoperative Radiotherapy Based on the 11th Japanese Classification for Esophageal Carcinoma After Curative Resection: A Propensity Score-Matched Analysis.

OBJECTIVE: The aim of this study was to compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) staging system with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on a substage of the JES staging system. METHODS: Area under the curve (AUC) values of the receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus PORT [S+RT group]) across substages of the 11th JES staging system according to independent prognostic factors for overall survival (OS) identified using Cox proportional hazards regression. RESULTS: A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC staging system was significantly higher than that for the 11th JES staging system (0.701 vs. 0.675, p < 0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (p < 0.001) and 21.1% (p < 0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; p < 0.001). CONCLUSION: The 11th JES staging system was less capable of predicting prognosis than the 8th AJCC staging system and patients in stage III of the JES staging system were highly recommended to undergo PORT.

Spatially dependent hyper-Raman scattering in five-level cold atoms.

We demonstrate a scheme to control the spatially dependent hyper-Raman scattering based on electromagnetically induced transparency in a cold atomic system. By adjusting the different system parameters, one can effectively modulate the phase and intensity of the generated Raman field. Specifically, we show that electromagnetically induced transparency creates quantum interference, which results in greatly enhanced efficiency for the generated Raman field. Such improvement in Raman efficiency makes our scheme suitable for generation of short-wavelength coherent radiation, conversion of frequency, and nonlinear spectroscopy based on orbital angular momentum light.

miR-30b-5p inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting GALNT7 via the EGFR/PI3K/AKT pathway.

BACKGROUND: Papillary thyroid carcinoma (PTC) is a common endocrine tumor. Increasing evidence has shown that microRNA dysfunction is involved in the occurrence and development of cancer. The expression of MicroRNA-30b-5p (miR-30b-5p) was down-regulated in PTC; however, its role in the development of PTC is not clear. Hence, this study aimed to explore the role and mechanism of miR-30b-5p in the occurrence and development of PTC. METHODS: The qRT-PCR assay was used to detect the expression of miR-30b-5p in 60 cases of papillary thyroid carcinoma along with their matched non-cancerous tissues. This study explored the biological function of miR-30b-5p by the functional gain and loss experiments in vitro and vivo. The direct target gene of miR-30b-5p and its signaling pathway was identified through bioinformatics analysis, qRT-PCR, western blot, rescue experiments, and double luciferase 3'-UTR report analysis. RESULTS: This study demonstrated that the low expression of miR-30b-5p is related to poor clinicopathological features. Functionally, the overexpression of miR-30b-5p inhibited the proliferation, invasion, and migration of PTC cells. Bioinformatics and luciferase analysis showed that GALNT7 is the direct and functional target of miR-30b-5p. Moreover, miR-30b-5p inhibited the proliferation of PTC in vivo by inhibiting the expression of GALNT7. The studies on the mechanism have shown that GALNT7 promotes cell proliferation and invasion by activating EGFR/PI3K/AKT kinase pathway, which can be attenuated by the kinase inhibitors. CONCLUSIONS: Overall, miR-30b-5p inhibited the progression of papillary thyroid carcinoma by targeting GALNT7 and inhibiting the EGFR/PI3K/AKT pathway.

Primary gross tumor volume is prognostic and suggests treatment in upper esophageal cancer.

BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

Clinical practice and outcome of radiotherapy for advanced esophageal squamous cell carcinoma between 2002 and 2018 in China: the multi-center 3JECROG Survey.

PURPOSE: To determine the survival and prognostic factors of esophageal squamous cell carcinoma (ESCC) patients undergoing radical (chemo)radiotherapy in the era of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) in China. MATERIAL AND METHODS: The Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) conducted the first nationwide survey of nine institutions. Detailed information was accumulated on 5185 patients with ESCC who received definitive 3DCRT/IMRT between 2002 and 2018. Relevant prognostic factors were evaluated to assess their influence on overall and progression-free survivals. RESULTS: After a median follow-up time of 47.0 (0.9-157.4) months, the 1-year, 2-year, 3-year and 5-year overall survival rates of the whole group were 69.8%, 46.6%, 37.9% and 30.1%. The 1-year, 2-year, 3-year, and 5-year progression-free survival rates were 54.1%, 36.6%, 30.5% and 24.9%. Multivariate analysis demonstrated that sex, clinical stage, treatment modality and radiation dose were prognostic factors for OS. The survival of patients who received concurrent chemoradiotherapy (CCRT) was better than that of patients who received radiotherapy alone or sequential chemoradiotherapy. Patients receiving adjuvant chemotherapy after CCRT had a better OS than patients receiving CCRT alone. Patients receiving higher radiation dose had a better OS than those patients receiving low-dose radiotherapy. CONCLUSIONS: The survival of ESCC patients undergoing radical (chemo)radiotherapy was relatively satisfactory in the era of 3DCRTand IMRT. As the largest-scale multicenter research on esophageal cancer radiotherapy conducted in China, this study establishes national benchmarks and helps to provide references for subsequent related researches.

Local therapy for oligometastatic esophageal squamous cell carcinoma: a prospective, randomized, Phase II clinical trial.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).

Lay abstract The ESO-Shanghai 13 trial is a prospective, multicenter, randomized, Phase II trial to assess the impact of combined local treatment (such as radiotherapy, surgery and thermal ablation) and chemical drugs for patients with esophageal squamous cell carcinoma. Patients with four or less metastases and controlled esophageal lesion will be enrolled. The authors will recruit a total of 102 patients over 3 years from approximately five centers. All patients will be randomized and receive either chemical drugs alone or chemical drugs plus local treatment with the same probability. Patients will then be observed after treatment until disease progression or death or the end of the trial. Patients will need to report their symptoms and physical status and fill out quality of life scales during the treatment and follow-up period.

Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

Magnetic resonance imaging (MRI) radiomics of papillary thyroid cancer (PTC): a comparison of predictive performance of multiple classifiers modeling to identify cervical lymph node metastases before surgery.

PURPOSE: To compare predictive efficiency of multiple classifiers modeling and establish a combined magnetic resonance imaging (MRI) radiomics model for identifying lymph node (LN) metastases of papillary thyroid cancer (PTC) preoperatively. MATERIALS AND METHODS: A retrospective analysis based on the preoperative MRI scans of 109 PTC patients including 77 patients with LN metastases and 32 patients without metastases was conducted, and we divided enroll cases into trained group and validation group. Radiomics signatures were selected from fat-suppressed T2-weighted MRI images, and the optimal characteristics were confirmed by spearman correlation test, hypothesis testing and random forest methods, and then, eight predictive models were constructed by eight classifiers. The receiver operating characteristic (ROC) curves analysis were performed to demonstrate the effectiveness of the models. RESULTS: The area under the curve (AUC) of ROC based on MRI texture diagnosed LN status by naked eye was 0.739 (sensitivity = 0.571, specificity = 0.906). Based on the 5 optimal signatures, the best AUC of MRI radiomics model by logistics regression classifier had a considerable prediction performance with AUCs 0.805 in trained group and 0.760 in validation group, respectively, and a combination of best radiomics model with visual diagnosis of MRI texture had a high AUC as 0.969 (sensitivity = 0.938, specificity = 1.000), suggesting combined model had a preferable diagnostic efficiency in evaluating LN metastases of PTC. CONCLUSION: Our combined radiomics model with visual diagnosis could be a potentially effective strategy to preoperatively predict LN metastases in PTC patients before clinical intervention.

Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis.

BACKGROUND: To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. METHODS: Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. RESULTS: A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16-1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15-1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. CONCLUSIONS: Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

Does chemoradiotherapy benefit elderly patients with esophageal squamous cell cancer? A propensity-score matched analysis on multicenter data (3JECROG R-03A).

BACKGROUND: The aim of the present study was to assess the efficacy of concurrent chemoradiotherapy (CRT) or radiotherapy alone (RT-alone) in elderly patients with esophageal squamous cell carcinoma (ESCC). METHODS: The clinical data of patients with ESCC treated with RT-alone or CRT were collected and retrospectively reviewed. The 1-, 3- and 5-year overall survival (OS) rates and the clinical characteristics correlated with survival were analyzed statistically. Propensity score matching (PSM) analyses were used to compensate for differences in baseline characteristics between the CRT and RT-alone groups to confirm the survival difference. RESULTS: A total of 729 patients fulfilling the inclusion criteria were reviewed. Diabetes, primary tumor volume (pTV), primary tumor location (pTLo), clinical T stage,(cT) clinical N stage (cN), clinical M stage (cM) and short-term response to RT were independent factors influencing OS (P = 0.002-0.044). The 5-year OS rate was 26.6, 26.0 and 30.1% in the whole cohort, RT-alone and CRT groups, respectively. The survival difference between RT alone and CRT was not significant before or following PSM. Compared with the corresponding subgroups treated with RT alone, CRT significantly benefited patients with diabetes (P = 0.003), cT4 (P = 0.030) and cN0 (P = 0.049), whereas no benefit was identified between CRT and RT alone in the other subgroups, including cT1-3, cN1, cM, pTLo, pTV, age and gender. CONCLUSIONS: CRT with the current chemotherapy regimens may not improve the survival of elderly ESCC patients compared to RT-alone, except in patients with cT4 stage, cN0 stage or diabetes. However, due to the limitation of the retrospective nature of the current study, further clinical trials are required for confirmation.