Background Prospective data is limited on the efficacy fi cacy and safety of consolidative stereotactic radiotherapy (SRT) in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients harboring oligo-residual disease (ORD) after fi rst-line third-generation EGFR-tyrosine kinase inhibitors (TKIs). Methods In this single-arm, phase II trial, 61 patients from two academic centers were enrolled from March 2021 to March 2023. All these patients had metastatic EGFR-mutant NSCLC and harbored ORD after first-line third- generation EGFR-TKIs. Consolidative SRT was performed and EGFR-TKIs were not held during SRT. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival and treatment-related adverse events (TRAEs). A prespecified fi ed propensity score matched (PSM) comparison was conducted with a contemporary cohort of patients who developed ORD but received EGFR-TKIs alone. This trial was registered with ClinicalTrails.gov, NCT04764214. Findings All patients received consolidative SRT. With a median follow-up of 21.1 months, the median PFS was 29.9 (80% CI 22.4-32.4) - 32.4) months and the lower boundary exceeded the predefined fi ned threshold, meeting the primary endpoint. TRAEs occurred in 43 (70%) patients, with pneumonitis (27.9%) and esophagitis (26.2%) being the most common toxicities. Four patients (6.6%) reported grade >= 3 TRAEs, each for pneumonitis, esophagitis, leukopenia, and cranial radiation necrosis. PSM analysis showed significantly fi cantly prolonged PFS in EGFR-TKI + SRT group compared to EGFR-TKI group (HR 0.46, 80% CI 0.20-0.61; - 0.61; p = 0.002). Interpretation Consolidative SRT is associated with an encouraging PFS in fi rst-line third-generation EGFR-TKItreated metastatic NSCLC patients harboring ORD, with generally acceptable toxicities. Further confirmatory fi rmatory studies are warranted. Funding Hui Lan Public Welfare and the Chinese Society of Clinical Oncology Foundation. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. Objectives: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. Design: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. Methods: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. Results: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 ( p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy ( p = 0.010). Conclusion: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Background: Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose: To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods: This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B -mode US of the liver between January 2014 and September 2022 at three health care facilities. A US -based DL network (FIB -Net) was trained on US images to predict whether the shear -wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis -4 Index (FIB -4) followed by FIB -Net and a three -step algorithm (Three-step#1) using FIB -4 followed by FIB -Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB -4, SWE, FIB -Net, and European Association for the Study of the Liver guidelines (ie, FIB -4 followed by SWE), along with sequential algorithms. Results: The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB -Net obtained a noninferior specificity with a margin of 5% ( P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB -4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion: A sequential algorithm combining FIB -4 and a US DL model showed higher diagnostic accuracy and improved referral management for all -cause advanced liver fibrosis compared with FIB -4 or the DL model alone.

Lesion localization and tracking are critical for accurate, automated medical imaging analysis. Contrast-enhanced ultrasound (CEUS) significantly enriches traditional B-mode ultrasound with contrast agents to provide high-resolution, real-time images of blood flow in tissues and organs. However, many trackers, designed primarily for natural RGB or B-mode ultrasound images, underutilize the extensive data from dual-screen enhanced images and fail to account for respiratory motion, thus facing challenges in achieving accurate target tracking. To address the existing challenges, we propose an adaptive-weighted dual mapping (ADMNet), an online tracking framework tailored for CEUS. Firstly, we introduced a novel Multimodal Atrous Attention Fusion (MAAF) module, innovatively designed to adapt the weightage between B-mode and enhanced images in dual-screen CEUS, reflecting the clinician's dynamic focus shifts between screens. Secondly, we proposed a Respiratory Motion Compensation (RMC) module to correct motion trajectory interferences due to respiratory motion, effectively leveraging temporal information. We utilized two newly established CEUS datasets, totaling 35,082 frames, to benchmark the ADMNet against various advanced B-mode ultrasound trackers. Our extensive experiments revealed that ADMNet achieves new state-of-the-art performance in CEUS tracking. Ablation studies and visualizations further underline the effectiveness of MAAF and RMC modules, demonstrating the promising potential of ADMNet in clinical CEUS tracing, thus providing novel research avenues in this field.

Prunella vulgaris is a traditional Chinese herbal medicine with many pharmacological effects, among which the anti-inflammatory effect is more significant. It is widely reported that Prunella vulgaris has anti-inflammatory, antioxidant, immune regulation, intestinal flora regulation and intestinal barrier protection effects on ulcerative colitis (UC). This paper collected relevant reports to further summarize the mechanisms and effective parts of Prunella vulgaris and its monomers in the treatment of UC and provided theoretical basis and reference for the application of Prunella vulgaris in UC.

BACKGROUND:Immune checkpoint inhibitor (ICI) monotherapy and neoadjuvant immunochemotherapy have shown promising results in esophageal carcinoma. However, it is still unclear whether more courses of immunochemotherapy are therapeutically better. We aimed to investigate the safety and efficacy of three courses of neoadjuvant treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC).METHODS:Patients with locally advanced ESCC received three courses of camrelizumab plus nab-paclitaxel and capecitabine before undergoing surgery. Additionally, patients received safety, computed tomography (CT), and endoscopy (with endoscopic ultrasonography and mucosal biopsy) assessments before and in the second and third courses of treatment. We used the CT and endoscopic assessment results from the second and third courses for comparison.RESULTS:From May 2020 to December 2021, 47 patients were enrolled at Sun Yat-sen University Cancer Center. In our study, 43 patients completed three courses of preoperative chemotherapy combined with anti-Programmed cell death-1 (PD-1) therapy and radical surgical resection. The toxicity of the third course of immunochemotherapy was mild and well tolerated without increased treatment-related adverse events (TRAEs) and mortality compared with that of the second course of treatment. In terms of efficacy, an additional course of treatment after the second course of treatment was effective, with increased CT and endoscopy T (clinical T stage) downstaging rates by 16.3% and 25.9%, N (clincial N stage) downstaging rates by 7.0% and 11.1%, and objective response rates (ORRs) by 13.6% and 22.0%, respectively.CONCLUSIONS:Regardless of downstaging or ORR, three courses of immunochemotherapy appear to be superior to two courses of treatment without increasing TRAEs.

Long-term tumour recurrence rates and complications of endoscope-assisted partial superficial parotidectomy (PSP) are rarely reported compared to traditional open approaches. This retrospective study included 306 patients with superficial parotid benign neoplasms who were divided into an endoscopy group (endoscope-assisted PSP, n = 102) and a control group (conventional PSP, n = 204). There were no significant differences in clinical and pathological characteristics between the two groups, except age (P = 0.001). Three patients had confirmed recurrence during a mean follow-up duration of 125.1 months. Ten (9.8%) patients in the endoscopy group and 22 (10.8%) in the control group developed transient facial nerve palsy (P = 0.792), and recovered 6 months after the operation. Nine (8.8%) and 19 (9.3%) patients, respectively, suffered from Frey syndrome (P = 0.889). A sensory deficit of the auricle occurred in 24 (23.5%) and 57 (27.9%) patients respectively (P = 0.410). Patients in the endoscopy group were more satisfied with the postoperative scar than those in the control group (P < 0.001). This study demonstrated that the endoscopeassisted PSP can be curative, with better cosmetic outcomes than the conventional approach, and does not increase the incidence of postoperative complications or the local recurrence rate.

Abstract Background To investigate the impact of station 3A lymph node dissection (LND) on overall survival (OS) and disease‐free survival (DFS) in completely resected right‐side non‐small‐cell lung cancer (NSCLC) patients. Methods A total of 1661 cases with completely resected right‐side NSCLC were included. Propensity score matching (PSM) was performed to minimize selection bias, and a logistic regression model was conducted to investigate the risk factors associated with station 3A lymph node metastasis (LNM). The Kaplan–Meier method and Cox proportional hazards model were used to evaluate the impact of station 3A LND on survival. Results For the entire cohort, 503 patients (30.3%) underwent station 3A LND. Of those, 11.3% (57/503) presented station 3A LNM. Univariate and multivariate logistic analyses showed that station 10 LNM, tumor location, and the number of resected lymph nodes were independent risk factors associated with station 3A LNM. Before PSM, patients with station 3A LND had worse 5‐year OS (p = 0.002) and DFS (p = 0.011), and more drainage on postoperative day 1 (p = 0.041) than those without. After PSM, however, station 3A LND was not associated with the 5‐year OS (65.7% vs. 63.6%, p = 0.432) or DFS (57.4% vs. 56.0%, p = 0.437). The multivariate analysis further confirmed that station 3A LND was not a prognostic factor (OS, p = 0.361; DFS, p = 0.447). Conclusions Station 3A LND could not improve long‐term outcomes and it was unnecessary to dissect station 3A lymph nodes during surgery of right‐side NSCLC.

BACKGROUND The effectiveness and survival benefit of minimally invasive esophagectomy compared to open esophagectomy (OE) remain controversial. The aim of this study was to evaluate the safety, efficacy, and oncologic outcomes of McKeown's total minimally invasive esophagectomy (tMIE) and McKeown's OE in the treatment of patients with esophageal squamous cell carcinoma. METHODS A series of 917 consecutive patients (306 OE and 611 tMIE) who underwent McKeown's esophagectomy for esophageal squamous cell carcinoma in the Department of Thoracic Surgery at Sun Yat-sen University Cancer Center from January 2011 to December 2016 were evaluated. We performed propensity matching between the tMIE and OE groups on the basis of estimated propensity scores for each patient. RESULTS After propensity-matched analysis, 288 patients were selected from each group. The rate of postoperative complications, such as pneumonia, respiratory insufficiency, cervical anastomotic leakage, and wound infection, in the OE group was significantly higher than that in the tMIE group. lntraoperative blood loss and operative duration were not significantly different between the matched groups, whereas the tMIE group had a shorter length of intensive care unit stay and postoperative hospital stay than the OE group. The IRO resection rate and the number of lymph nodes harvested were not significantly different between groups. There was no significant difference in median overall survival between the 2 groups after matching. CONCLUSIONS McKeown's tMIE was shown to be a safe and effective procedure with long-term survival comparable to that of OE for the patients with esophageal squamous cell carcinoma. (C) 2022 by The Society of Thoracic Surgeons

Introduction: the investigation on the interactions between ferroptosis and lncRNAs for lung squamous cell carcinoma (LUSC) has been scare, and its impact on tumor immune microenvironment remained unknown. We aim to not only identify a ferroptosis-related lncRNAs signature for LUSC prognosis, but also evaluate its correlation to tumor immune evasion.Methods: RNA sequencing data and survival information were obtained from The Cancer Genome Atlas database. A ferroptosis-related lncRNAs signature (FerRLSig) was developed and validated by univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression and multivariate Cox regression. The tumor immune microenvironment and immune evasion were subsequently evaluated based on the FerRLSig stratification.Results: the FerRLSig consisted of 10 ferroptosis-related lncRNAs and significantly associated with overall survival with satisfactory area under curve (HR = 2.240, 95% CI: 1.845–2.720, p < 0.001, 5-years AUC: 0.756). Based on the FerRLSig stratification, the high-risk group demonstrated not only significantly higher immune infiltration, but also more profound T cell dysfunction and immune evasion, which might ultimately lead to the resistance to current immune checkpoint inhibitors.Conclusion: a robust prognostic FerRLSig for LUSC has been developed and validated, demonstrating a close association not only with tumor immune cell infiltration, but also with T cell dysfunction and immune evasion. Further investigation is warranted to better improve the survival of LUSC patients based on the FerRLSig stratification.

Background: Head and neck squamous cell carcinoma (HNSC) is the 7th most common type of cancer in the world. Through the advantages of The Cancer Genome Atlas (TCGA) large-scale sequencing-based genome analysis technology, we can explore the potential molecular mechanisms that can improve the prognosis of HNSC patients. Methods: The HNSC transcriptome and clinical data were downloaded from TCGA database. A univariate survival analysis and differential expression analysis were conducted to obtain the intersection gene set. A protein-protein interaction (PPI) analysis, modular analysis, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were then conducted to identify the hub genes. Clinical correlation analysis, univariate and multivariate Cox regression analyses were performed on the identified hub genes to determine the prognostic impact of hub genes on HNSC patients. Results: In total, 601 intersecting gene sets were obtained. A modular analysis was conducted, and the highest scoring module was 19.304. Based on the GO/KEGG enrichment analysis results, CD247 molecule (CD247) was ultimately selected as the gene for this study. The CD247 were divided into a high-expression group and a low-expression group. The Kaplan-Meier survival curve analysis showed that there was a significant difference between the 2 groups (P<0.0001). The median survival time of the low-expression CD247 group was 30.9 months, and the 5-year survival rate was 36.4%. While the median survival time of the high-expression CD247 group was 68.8 months, and the 5-year survival rate was 52.3%. The clinical correlation analysis showed that CD247 was significantly negatively correlated with pathological tumor stage (pT) and pathological nodal extracapsular spread. Gene Set Enrichment Analysis (GSEA) showed that CD247 activating KEGG pathway hsa04650 and hsa04660. Conclusions: CD247 is an independent protective factor in the prognosis of HNSC patients. By activating the hsa04650 and hsa04660 pathways, the expression of interferon gamma, interleukin (IL)-2, and IL-10 is promoted, which in turn improves the tumor immune monitoring ability of the body, induces tumor cell apoptosis, and inhibits tumor cell growth. CD247 is a potential target for improving the clinical treatment effect of I INSC and the prognosis of patients.

Background: Malignant pleural mesothelioma (MPM) is a malignant tumor originating from pleural mesothelial cells and has a high mortality rate worldwide. With the advent of immunotherapy in MPM treatment, there is an urgent need to elucidate the immune-related mechanisms in this caner.Methods: Single-sample gene set enrichment analysis (ssGSEA) was used to score the immunocytes infiltration of data from different database sources. Identification of immunocyte-related genes was performed with weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, and correlation analysis. Pan-caner analysis was performed using "DiffExp" and "Correlation" modules in TIMER.Results: T-helper 2 (Th2) cell was found to be a poor prognostic factor for patients with MPM. Then a transcription factor, NFE2L3, was identified as a biomarker that showed a strong positive correlation with Th2 cell infiltration, and was highly expressed in MPM tissues and was related to the poor prognosis of these patients. At the same time, multiple NFE2L3 methylation sites were negatively correlated with Th2 cell infiltration, and patients with a high degree of methylation enjoy a better prognosis. Pan-caner analysis indicated that NFE2L3 might promote the differentiation of Th2 cells through the IL-2/STAT5/NLRP3 signaling pathway in MPM and many other cancers.Conclusion: We believe that NFE2L3 can serve as a potential biomarker related to the diagnosis and prognosis of patients with MPM, and speculate that NFE2L3 could promote Th2 cell differentiation via IL-2/STAT5/NLRP3 signaling pathway in MPM and many other cancers.

Background: The benefit of adjuvant chemotherapy (ACT) in pathological T2N0M0 non-small-cell lung cancer (NSCLC) patients is not clear. Methods: One thousand and fifty pathological T2N0M0 NSCLC patients were included and divided into two groups: with and without ACT. A propensity score matching analysis was carried out to minimize selection bias. The significance of ACT in high-risk patients was further analyzed. The Kaplan-Meier method and Cox proportional hazards model were used to assess the impact of ACT on the overall survival (OS), disease-free survival (DFS), and cancer-specific survival. Results: For the entire cohort, 31.9% (335/1050) of patients received ACT. After propensity score matching, 325 pairs of patients were matched. OS and DFS were comparable between groups in the original or matched cohort, which was confirmed by the multivariate analysis (all P > 0.05). In high-risk patients, the data suggest that ACT could improve OS and DFS only in patients with tumours >4 cm (OS: P = 0.003; DFS: P = 0.013). ACT could significantly improve the 5-year OS in patients with wild-type epidermal growth factor receptor (EGFR) (P = 0.022). ACT, however, could not improve cancer-specific survival in any subgroup, including patients with tumours >4 cm or wild-type EGFR (all P > 0.05). For patients with other high-risk factors, ACT failed to benefit patients in long-term outcomes. Conclusions: In resected pT2N0M0 NSCLC patients, those with tumours >4 cm and wild-type EGFR are real high-risk patients and could gain survival benefit from ACT. Further prospective study is needed to confirm the definition.

AIM:To establish an ultrasound-based radiomics model through machine learning methods and then to assess the ability of the model to differentiate infected focal liver lesions from malignant mimickers. MATERIALS AND METHODS:A total of 104 patients with infected focal liver lesions and 485 patients with malignant hepatic tumours were included, consisting of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), combined hepatocellular-cholangiocarcinoma (cHCC-CC), and liver metastasis. Radiomics features were extracted from grey-scale ultrasound images. Feature selection and predictive modelling were carried out by dimensionality reduction methods and classifiers. The diagnostic effect of the prediction mode was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS:In total, 5,234 radiomics features were extracted from grey-scale ultrasound image of every focal liver lesion. The ultrasound-based radiomics model had a favourable predictive value for differentiating infected focal liver lesions from malignant hepatic tumours, with an area under the curve (AUC) of 0.887 and 0.836 (HCC group), 0.896 and 0.766 (CC group), 0.944 and 0.754 (cHCC-CC group), 0.918 and 0.808 (liver metastasis group), and 0.949 and 0.745 (malignant hepatic tumour group) for the training set and validation set, respectively. CONCLUSIONS:Ultrasound-based radiomics is helpful in differentiating infected focal liver lesions from malignant mimickers and has the potential for use as a supplement to conventional grey-scale ultrasound and contrast-enhanced ultrasound (CEUS).

Background Oesophageal squamous cell carcinoma (ESCC) is a malignant tumour of the digestive system that is associated with high morbidity and mortality rates worldwide. With the increased use of immunotherapy in cancer treatment, there is an urgent need to elucidate the immune-related mechanisms in ESCC and other digestive system carcinomas. Methods In our study, single-sample gene set enrichment analysis (ssGSEA) was first performed to analyse the expression profile downloaded from the NCBI Gene Expression Omnibus (GEO) database. Then, via a series of bioinformatic analyses, including the Mann-Whitney test, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and differentially expressed genes (DEGs) analysis, we identified target immunocytes and related genes. Finally, we validated the results with the TIMER database. Results Our analyses showed that the numbers of infiltrating macrophages were obviously higher in advanced stages in ESCC compared with other types of immunocytes. MEOX2 was identified as a biomarker correlated with macrophage infiltration in ESCC and other types of digestive system carcinomas. And MEOX2 expression was strongly associated with the mRNA expression of colony-stimulating factor 1 (CSF-1) and CSF-1 receptor (CSF-1R) in these kinds of carcinomas. Conclusion We speculated that MEOX2 could facilitate macrophage infiltration via CSF-1/CSF-1R signalling in ESCC and other kinds of digestive system carcinomas, and MEOX2 might serve as a novel target in prospective tumour immunotherapies.

OBJECTIVE:This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS:ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS:Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI): 0-20.3] than those with low-risk scores (50.3%, 95% CI: 40.0-60.7; P < 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P < 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION:Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.

BACKGROUND:To explore the key genes in renal tubular necrosis.METHODS:Microarray datasets GSE69644, GSE27168, and GSE2027 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and we performed functional enrichment analysis. The network of protein interaction and gene interaction was constructed, and the module analysis was conducted using Cytoscape.RESULTS:A total of 543 DEGs and 13 hub genes were identified. The correlation analysis between the hub genes and the clinical characteristics of tubular necrosis indicated that the patients with high expression of SPAG5 and BIRC5 had better renal function. Patients with high expression of KIF14, KIF20A, MAD2L1, CKAP2, CDC25C, and CENPEN had poor renal function. Four of those hub genes participate in the cell cycle, apoptosis, and mismatch repair by regulating important genes in the pathway.CONCLUSIONS:Our study suggests that CDC25C, MAD2L, BIRC5, and EXO1 participate in the cell cycle, apoptosis, and mismatch repair during renal tubule necrosis (RTN) and have an impact on renal function.

AIM:To investigate the effect of radiomics in the assessment of alterations in canonical cancer pathways in breast cancer. MATERIALS AND METHODS:Eighty-eight biopsy-proven breast cancer cases were included in the present study. Radiomics features were extracted from T1-weighted sagittal dynamic contrast-enhanced magnetic resonance imaging (MRI) images. Radiomics signatures were developed to predict genetic alterations in the cell cycle, Myc, PI3K, RTK/RAS, and p53 signalling pathways by using hypothesis testing combined with least absolute shrinkage and selection operator (LASSO) regression analysis. The predictive powers of the models were examined by the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS:A total of 5,234 radiomics features were obtained from MRI images based on the tumour region of interest. Hypothesis tests screened 250, 229, 156, 785, and 319 radiomics features that were differentially displayed between cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations and no alteration status. According to the LASSO algorithm, 11, 12, 12, 15, and 13 features were identified for the construction of the radiomics signatures to predict cell cycle, Myc, PI3K, RTK/RAS, and p53 alterations, with AUC values of 0.933, 0.926, 0.956, 0.940, and 0.886, respectively. The cell cycle radiomics score correlated closely with the RTK/RAS and p53 radiomics scores. These signatures were also dysregulated in patients with different oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 statuses. CONCLUSION:MRI-based radiogenomics analysis exhibits excellent performance in predicting genetic pathways alterations, thus providing a novel approach for non-invasively obtaining genetic-level molecular characteristics of tumours.

BACKGROUND:Transcription factor AP-2 alpha (TFAP2A) has been reported to participate in various tumors. However, the transcriptional levels and prognostic values of TFAP2A remain elusive in lung adenocarcinoma (LUAD). The purpose of the present study was to investigate the impact of the TFAP2A in LUAD.METHODS:The transcriptional levels and prognostic effects of TFAP2A were explored in patients with LUAD using various online databases, including the GEPIA, Oncomine, and Kaplan-Meier plotter databases. Meanwhile, meta-analyses were performed to verify the expression levels and prognostic effects of TFAP2A in LUAD using the Lung Cancer Explorer (LCE) database. In addition, target genes of TFAP2A were identified in the Animal TFDB3.0 dataset.RESULTS:Our comprehensively study indicated the mRNA expression levels of TFAP2A in LUAD were significantly higher than that of normal controls. In the survival analyses, higher TFAP2A levels were related to the shortened survival time of patients with LUAD. Meanwhile, the meta-analyses based on the LCE database also suggested the overexpressed TFAP2A led to worsen prognosis of patients with LUAD. Finally, the cell division cycle 6 (CDC6) and aurora kinase A (AURKA) were regarded as two target genes of TFAP2A.CONCLUSIONS:We have performed comprehensive analyses for TFAP2A in patients with LUAD. Patients with higher TFAP2A levels demonstrated worsen prognosis than those with lower TFAP2A levels. The CDC6 and AURKA might be two target genes of TFAP2A. Further molecular biological experiments were required to study the mechanisms of TFAP2A in LUAD.

Background: Esophageal squamous cell carcinoma (ESCC) is the main histological subtype of esophageal cancer. However, the postoperative prognosis of patients with ESCC remains challenging. No studies have focused on quantitative analysis of CT and pathological images to personalize the prognosis of patients who undergo surgery. Herein we evaluated the effectiveness of such novel analyses for predicting the postoperative prognosis of ESCC. Methods: Data of 153 patients with ESCC who underwent esophagectomy. were retrospectively reviewed. We quantitatively analyzed the digital histological specimens and diagnostic CT images. We cut; the pathological images (6000 × 6000) of each case were cut into 50 × 50 patches; each case had a total of 14,400 patches.. Cluster analysis was used to process these patches, and 20; 20 features were obtained with the pathological patches cluster ratio (PPCR) features were presented. A total of 125 computerized quantitative features were extracted, including 20 PPCR features and 105 CT features. We used the approach of recursive feature elimination to select features. A Cox hazard model with L1 penalization (LASSO-COX) was used for prognostic indexing. We compared the following four different were extracted. Four prognostic models: were compared. Model A: using clinical features alone; Model B: using quantitative CT and clinical features; Model C: using quantitative histopathological and clinical features; and Model D: using combined information from all three sources (clinical, CT, and histopathology) features. For model selection, we performed leave-one-out cross -validation with feature selection. Indices of Prognostic-model accuracy was assessed by the indices of concordance (C-index) were used to assess the accuracy of the prognostic models.indices). Findings: Five PPCR and eight CT features were treated as significant indicators in ESCC prognosis. The C-indices of Model D were the highest for training (0·77) and validation (0·711). Using the Model D C-index, we stratified the patients into low- and high-risk groups. The 1- and 3-year overall survival rates of low-risk patients were 82·0% and 38·0%, respectively, and those of high-risk patients were 67·0% and 25·0%, respectively (p<0·001). Interpretation: A quantitative prognostic model combining clinical, histopathological, and diagnostic CT data can stratify patients with ESCC into high- and low-risk groups, improving the prognosis prediction of these patients postoperatively.Funding Statement: In part by the National Key R&D Program of China (2018YFC1704206), National Natural Science Foundation of China (81971691, 81830052, U1811461), and Science and Technology Innovative Project of Guangdong Province (2016B030307003).Declaration of Interests: The author(s) indicated no potential conflicts of interest.Ethics Approval Statement: The Ethics Committee of Sun Yat-sen University Cancer Center approved the study’s protocol (Approval No: GZR2019-161).