Intraoperative assessment of microimplantation-induced acute brain inflammation with titanium oxynitride-based plasmonic biosensor.

Implantable devices for brain-machine interfaces and managing neurological disorders have experienced rapid growth in recent years. Although functional implants offer significant benefits, issues related to transient trauma and long-term biocompatibility and safety are of significant concern. Acute inflammatory reaction in the brain tissue caused by microimplants is known to be an issue but remains poorly studied. This study presents the use of titanium oxynitride (TiNO) nanofilm with defined surface plasmon resonance (SPR) properties for point-of-care characterizing of acute inflammatory responses during robot-controlled micro-neuro-implantation. By leveraging surface-enriched oxynitride, TiNO nanofilms can be biomolecular-functionalized through silanization. This label-free TiNO-SPR biosensor exhibits a high sensitivity toward the inflammatory cytokine interleukin-6 with a detection limit down to 6.3 fg ml-1 and a short assay time of 25 min. Additionally, intraoperative monitoring of acute inflammatory responses during microelectrode implantation in the mice brain has been accomplished using the TiNO-SPR biosensors. Through intraoperative cerebrospinal fluid sampling and point-of-care plasmonic biosensing, the rhythm of acute inflammatory responses induced by the robot-controlled brain microelectrodes implantation has been successfully depicted, offering insights into intraoperative safety assessment of invasive brain-machine interfaces.

Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

Evaluation of risk factors for surgical site infections in osteoarthritis patients undergoing total knee arthroplasty.

This research sought to delineate risk factors associated with surgical site infections (SSIs) post-total knee arthroplasty (post-TKA) in elderly osteoarthritis patients, aiming to enhance post-surgical outcomes. A retrospective examination was conducted on a cohort of 650 elderly patients who underwent unilateral TKA between January 2018 and August 2022. Data procurement was from the hospital's Electronic Health Record, and a comprehensive statistical evaluation was performed using IBM SPSS Statistics version 24.0. Both univariate and multivariate techniques assessed a spectrum of risk determinants such as age, body mass index (BMI), coexisting medical conditions and surgical variables. The univariate examination spotlighted age, BMI, diabetes prevalence, chronic corticosteroid consumption and American Society of Anesthesiologists (ASA) physical status classification as notable predictors of SSIs. The multivariate logistic regression pinpointed age, BMI, history of smoking and diabetes diagnosis as salient risk attributors for post-TKA infections. Concurrently, parameters like ASA classification, surgical duration and intraoperative haemorrhage further enriched the risk landscape. Geriatric patients undergoing TKA for knee osteoarthritis manifest a tangible infection susceptibility post-surgery. Precision interventions concentrating on amendable risk components, including meticulous preoperative evaluations and strategic postoperative care, are imperative to attenuate SSI incidence, thereby amplifying surgical efficacy and optimizing patient recuperation trajectories.

Identification of an optimized glycolytic-related risk signature for predicting the prognosis in breast cancer using integrated bioinformatic analysis.

Aberrant metabolic disorders and significant glycolytic alterations in tumor tissues and cells are hallmarks of breast cancer (BC) progression. This study aims to elucidate the key biomarkers and pathways mediating abnormal glycolysis in breast cancer using bioinformatics analysis. Differential genes expression analysis, gene ontology analysis, Kyoto encyclopedia of genes and genomes analysis, gene set enrichment analyses, and correlation analysis were performed to explore the expression and prognostic implications of glycolysis-related genes. We effectively integrated 4 genes to construct a prognostic model of shorter survival in the high-risk versus low-risk group. The prognostic model showed promising predictive value and may be an integral part of the prognosis of BC. The survival analysis and receiver operating characteristic curves suggested that the signature showed a good predictive performance in both the The Cancer Genome Atlas training set and 2 gene expression omnibus validation sets. Multivariable analysis demonstrated that the 4-gene signature had an independent prognostic value. Furthermore, all calibration curves exhibited robust validity in prognostic prediction. We established an optimized 4-gene signature to clarify the connection between glycolysis and BC, and offered an attractive platform for risk stratification and prognosis predication of BC patients.

Symptomatic secondary spinal arachnoid cysts: a systematic review.

BACKGROUND CONTEXT: Secondary spinal arachnoid cysts have rarely been reported but present significant challenges for management. These cysts could be anteriorly located with long rostral-caudal extensions and many are related to arachnoiditis, leading to difficult-to-treat disorders. Thus far, due to the scarcity of reports, the features of the disease and the optimal therapeutic strategies remain unclear. PURPOSE: To investigate clinical features and the optimal treatment modalities of secondary spinal arachnoid cysts compared with primary spinal arachnoid cysts. STUDY DESIGN: Systematic review. PATIENT SAMPLE: Systematic review identified 103 secondary cases from 80 studies and reports. OUTCOME MEASURES: Condition of symptom relief and duration of treatment response were analyzed. METHODS: An electronic literature search of the PubMed database was conducted for studies on secondary spinal arachnoid cysts between 1990 and 2022. Non-English publications, nonhuman studies, reports of a primary cyst, studies not including case details, and studies of nonsymptomatic cases were excluded. RESULTS: This systematic review included 103 secondary cases. The most commonly reported etiologies were iatrogenic factors, trauma, and subarachnoid hemorrhage, accounting for 88 intradural extramedullary, 11 extradural, one intradural/extradural, one interdural, and one intramedullary spinal arachnoid cyst after a median duration of 30, 12, and 9 months, respectively. Extradural cysts were more prone to occur at dorsal locations and affect thoracic segments (mean cyst length: 3.4 segments). Intradural cysts showed a relatively higher ventral/dorsal ratio (1:1.09, 1.75:1, and 3.50:1 for cysts occurring from iatrogenic factors, trauma, and subarachnoid hemorrhage, respectively) and thoracic distribution, with a mean cyst length of 4.3 segments (5.1 for ventral and 3.5 for dorsal cysts). For intradural cysts, recurrence risk was lower after surgical resection than after fenestration/marsupialization (12-month recurrence risk: 21.43% vs 50.72%, log-rank test: p=.0248, Gehan-Breslow-Wilcoxon test: p=.0126). In cases treated with shunting, one recurrence (1/8 cases) was noted after external shunting and two recurrences (2/5 cases) after internal shunting at a median follow up of 12 months. CONCLUSIONS: Secondary spinal arachnoid cysts, particularly intradural cysts, are rarer and more challenging to treat than primary spinal cysts. Although fenestration/marsupialization is the commonly adopted treatment, the recurrence rate is high. For unresectable cysts, shunting procedures, particularly shunting into a body cavity (eg, pleural or peritoneal cavity) away from the subarachnoid space, could be a therapeutic alternative besides fenestration/marupialization, yet its efficacy requires confirmation by more data.

Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer.

Immune checkpoint inhibitors (ICIs) have become important treatment strategies, yet responses vary among patients and predictive biomarkers are urgently needed. Mutations in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/D mutations might be a predictor of immunotherapeutic efficacy. Here, we investigated the associations of KMT2C/D loss-of-function (LOF) variants with tumor mutation burden (TMB), MSI-H, PD-L1 expression, the levels of tumor-infiltrating leukocytes (TILs), and clinical response to ICIs. It was found that KMT2C/D LOF variants were associated with higher TMB. Compared with the non-LOF group, the proportion of patients with MSI-H tumors was larger in the LOF group. PD-L1 expression was higher in the LOF group only for colorectal cancer in both the Chinese and The Cancer Genome Atlas cohorts. Importantly, KMT2C/D LOF variants were associated with decreased regulatory T cells and increased levels of CD8+ T cells, activated NK cells, M1 macrophages, and M2 macrophages in colorectal cancer. However, there was no significant association between KMT2C/D LOF and TILs levels in other cancer types. Consistently, the results showed that KMT2C/D LOF variants were associated with prolonged overall survival only in colorectal cancer (p = 0.0485). We also presented that patients with KMT2C/D LOF mutations exhibited a better clinical response to anti-PD-1 therapy in a Chinese colorectal cancer cohort (p = 0.002). Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. In addition, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.

Identification of potential prognostic biomarkers among gene models for coiled-coil domain-containing family members in hepatocellular carcinoma elucidates their influence on the hypoxia pathway and immune microenvironment.

Background: The family of coiled-coil domain-containing (CCDC) proteins participates in a wide range of physiological functions and plays a pivotal role in governing the invasion and metastasis of malignant tumor cells. Nonetheless, the precise mechanism governing the interaction among the immune microenvironment, hypoxia pathway, and proliferation in hepatocellular carcinoma (HCC) remains elusive. In this study, our objective was to identify the prognostic significance of CCDC family genes in HCC. Methods: We conducted an analysis of RNA-seq data from HCC patients sourced from The Cancer Genome Atlas (TCGA) database. Our analysis involved comparing the expression profiles of 168 CCDC family genes between tumor and normal tissues to identify differentially expressed genes (DEGs). The prognostic value of these genes was verified using overall survival (OS) data from TCGA-LIHC patients, employing Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Subsequently, we constructed a prognostic signature known as the CCDC score and validated it using additional datasets (ICGC-LIRI-JP and GSE14520). Additionally, we performed functional enrichment analysis and conducted an assessment of the tumor immune microenvironment (TIME). Results: We identified 34 DEGs of the CCDC family. Among them, six DEGs (CCDC6/22/51/59/132/134) were upregulated and associated with poor prognosis. Higher CCDC score was an independent predictor of poor OS in TCGA-HCC patients (P<0.001, HR =2.37), which was validated in the ICGC-LIRI-JP (P=0.021, HR =2.15) and GSE14520 (P=0.002, HR =2.23) datasets. Functional enrichment analysis showed that hypoxia pathway genes were enriched in the high CCDC score group. Furthermore, immune microenvironment analysis demonstrated that high CCDC score was associated with a suppressed TIME caused by the extrinsic immune escape. Conclusions: The CCDC score, derived from six CCDC genes, exhibits remarkable expression levels in liver cancer and holds promise as an independent prognostic indicator. Our bioinformatics analysis revealed a high CCDC score is strongly associated with activation of the hypoxia pathway and an immunosuppressive tumor microenvironment in HCC. This profound finding may serve as a cornerstone for innovative targeted drug therapies and pave the way for further investigations into the underlying mechanisms of CCDC-related carcinogenesis in liver cancer.

Lateral ventricle pleomorphic xanthoastrocytoma concurrent with Dandy-Walker complex: A case report.

INTRODUCTION: Dandy-Walker complex and pleomorphic xanthoastrocytomas are both rare disease entities that typically manifest early in life and are associated with congenital etiological factors. Dandy-Walker complex is a cerebellar malformation associated with a series of anatomical changes. The disease onset is usually at birth or during infancy. Late onset in adulthood is uncommon. Pleomorphic xanthoastrocytoma is a rare WHO grade II astrocytic tumor affecting mainly young adults. Concomitant occurrence of Dandy-Walker complex and pleomorphic xanthoastrocytoma has not been previously reported. PATIENT CONCERNS AND DIAGNOSIS: A 30-year-old woman with a previous history of unconfirmed resected lateral ventricle meningioma presented with severe headache for 1 day. Imaging examination revealed a mass in the right lateral ventricle with heterogeneous signal patterns, changes in the posterior fossa corresponding to a Dandy-Walker variant, and mild hydrocephalus. INTERVENTIONS AND OUTCOMES: Surgical complete resection of the mass was achieved. postoperative histopathological examination confirmed WHO grade II pleomorphic xanthoastrocytoma. Three years postsurgery, ventriculoperitoneal shunt was performed due to worsening of hydrocephalus. The patient has since remained symptom-free. CONCLUSION: This is the first report of concomitant occurrence of Dandy-Walker complex and pleomorphic xanthoastrocytoma. The association of neurological congenital malformation with intracranial neoplasms may be multifactorial, with underlying role of genetic mutations or chromosome alterations.

Associations of genetic risk, BMI trajectories, and the risk of non-small cell lung cancer: a population-based cohort study.

BACKGROUND: Body mass index (BMI) has been found to be associated with a decreased risk of non-small cell lung cancer (NSCLC); however, the effect of BMI trajectories and potential interactions with genetic variants on NSCLC risk remain unknown. METHODS: Cox proportional hazards regression model was applied to assess the association between BMI trajectory and NSCLC risk in a cohort of 138,110 participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. One-sample Mendelian randomization (MR) analysis was further used to access the causality between BMI trajectories and NSCLC risk. Additionally, polygenic risk score (PRS) and genome-wide interaction analysis (GWIA) were used to evaluate the multiplicative interaction between BMI trajectories and genetic variants in NSCLC risk. RESULTS: Compared with individuals maintaining a stable normal BMI (n = 47,982, 34.74%), BMI trajectories from normal to overweight (n = 64,498, 46.70%), from normal to obese (n = 21,259, 15.39%), and from overweight to obese (n = 4,371, 3.16%) were associated with a decreased risk of NSCLC (hazard ratio [HR] for trend = 0.78, P < 2×10-16). An MR study using BMI trajectory associated with genetic variants revealed no significant association between BMI trajectories and NSCLC risk. Further analysis of PRS showed that a higher GWAS-identified PRS (PRSGWAS) was associated with an increased risk of NSCLC, while the interaction between BMI trajectories and PRSGWAS with the NSCLC risk was not significant (PsPRS= 0.863 and PwPRS= 0.704). In GWIA analysis, four independent susceptibility loci (P < 1×10-6) were found to be associated with BMI trajectories on NSCLC risk, including rs79297227 (12q14.1, located in SLC16A7, Pinteraction = 1.01×10-7), rs2336652 (3p22.3, near CLASP2, Pinteraction = 3.92×10-7), rs16018 (19p13.2, in CACNA1A, Pinteraction = 3.92×10-7), and rs4726760 (7q34, near BRAF, Pinteraction = 9.19×10-7). Functional annotation demonstrated that these loci may be involved in the development of NSCLC by regulating cell growth, differentiation, and inflammation. CONCLUSIONS: Our study has shown an association between BMI trajectories, genetic factors, and NSCLC risk. Interestingly, four novel genetic loci were identified to interact with BMI trajectories on NSCLC risk, providing more support for the aetiology research of NSCLC. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov , NCT01696968 .

Malignant Transformation and Metastatic Spread of Dumbbell-Shaped Meningeal Melanocytoma of the Cervical Spine: A Case Report and Literature Review.

Background: Meningeal melanocytoma is a rare disease that originates from leptomeningeal melanocytes in the central nervous system. Meningeal melanocytoma is generally considered benign, and has a good prognosis following complete surgical resection. Reports of the malignant transformation and spread of these tumors are scarce. Case Presentation: A 19 year old female presented with headache, progressive limb weakness, and dyspnea. Magnetic resonance imaging showed a dumbbell-shaped lesion at C1-C2 that was hyperintense on T1 weighted images and showed strong contrast enhancement. Total resection was achieved using a posterior midline approach. Post-operative pathology showed meningeal melanocytoma. The tumor recurred 9 months later with intracranial spread. Resection of the lesion revealed malignant transformation to meningeal melanoma. Conclusion: Meningeal melanocytoma harbors malignant potential even with total resection. Radiotherapy could be considered to prevent disease recurrence and progression.

Identification of RET fusions in a Chinese multicancer retrospective analysis by next-generation sequencing.

Fusion of RET with different partner genes has been detected in papillary thyroid, lung, colorectal, pancreatic, and breast cancer. Approval of selpercatinib for treatment of lung and thyroid cancer with RET gene mutations or fusions calls for studies to explore RET fusion partners and their eligibility for RET-based targeted therapy. In this study, RET fusion patterns in a large group of Chinese cancer patients covering several cancer types were identified using next-generation sequencing. A total of 44 fusion patterns were identified in the study cohort with KIF5B, CCDC6, and ERC1 being the most common RET fusion partners. Notably, 17 novel fusions were first reported in this study. Prevalence of functional RET fusions was 1.05% in lung cancer, 6.03% in thyroid cancer, 0.39% in colorectal cancer, and less than 0.1% in gastric cancer and hepatocellular carcinoma. Analysis showed a preference for fusion partners in different tumor types, with KIF5B being the common type in lung cancer, CCDC6 in thyroid cancer, and NCOA4 in colorectal cancer. Co-occurrence of EGFR mutations and RET fusions with rare partner genes (rather than KIF5B) in lung cancer patients was correlated with epidermal growth factor receptor-tyrosine kinase inhibitor resistance and could predict response to targeted therapies. Findings from this study provide a guide to clinicians in determining tumors with specific fusion patterns as candidates for RET targeted therapies.

A Multivariate Diagnostic Model Based on Urinary EpCAM-CD9-Positive Extracellular Vesicles for Prostate Cancer Diagnosis.

INTRODUCTION: Prostate cancer (PCa) is one of the most frequently diagnosed cancers and the leading cause of cancer death in males worldwide. Although prostate-specific antigen (PSA) screening has considerably improved the detection of PCa, it has also led to a dramatic increase in overdiagnosing indolent disease due to its low specificity. This study aimed to develop and validate a multivariate diagnostic model based on the urinary epithelial cell adhesion molecule (EpCAM)-CD9-positive extracellular vesicles (EVs) (uEVEpCAM-CD9) to improve the diagnosis of PCa. METHODS: We investigated the performance of uEVEpCAM-CD9 from urine samples of 193 participants (112 PCa patients, 55 benign prostatic hyperplasia patients, and 26 healthy donors) to diagnose PCa using our laboratory-developed chemiluminescent immunoassay. We applied machine learning to training sets and subsequently evaluated the multivariate diagnostic model based on uEVEpCAM-CD9 in validation sets. RESULTS: Results showed that uEVEpCAM-CD9 was able to distinguish PCa from controls, and a significant decrease of uEVEpCAM-CD9 was observed after prostatectomy. We further used a training set (N = 116) and constructed an exclusive multivariate diagnostic model based on uEVEpCAM-CD9, PSA, and other clinical parameters, which showed an enhanced diagnostic sensitivity and specificity and performed excellently to diagnose PCa [area under the curve (AUC) = 0.952, P < 0.0001]. When applied to a validation test (N = 77), the model achieved an AUC of 0.947 (P < 0.0001). Moreover, this diagnostic model also exhibited a superior diagnostic performance (AUC = 0.917, P < 0.0001) over PSA (AUC = 0.712, P = 0.0018) at the PSA gray zone. CONCLUSIONS: The multivariate model based on uEVEpCAM-CD9 achieved a notable diagnostic performance to diagnose PCa. In the future, this model may potentially be used to better select patients for prostate transrectal ultrasound (TRUS) biopsy.

Next Generation Sequencing Reveals Pathogenic and Actionable Genetic Alterations of Soft Tissue Sarcoma in Chinese Patients: A Single Center Experience.

Background: Next generation sequencing (NGS) has systematically investigated the genomic landscape of soft tissue sarcoma (STS) in Western patients, but few reports have described the utility of NGS in identifying pathogenic and targetable mutations in Asian patients. Methods: We review our single center experience of identifying the genomic profile and feasible genetic mutations in 65 Chinese patients with STS by NGS. Results: On average, 3.35 mutations were identified per patient (range, 0-28), and at least one mutation could be detected in 95.4% (62/65) of patients. TP53, MDM2, CDK4, KDR, and NF1 were the most frequent mutation genes in Chinese STS patients. Actionable mutations were discovered in 36.9% (24/65) of patients, and clinical benefit was achieved in 4 patients treated with corresponding molecular targeted therapies. Conclusions: Our study describes the mutation profile of Chinese STS patients by a single center experience. Some patients have achieved improved clinical outcomes by adopting treatment based on the results of genetic testing. NGS may affect clinical decision-making as a routine clinical test for patients with STS.

Glycolysis-related gene expression profiling serves as a novel prognosis risk predictor for human hepatocellular carcinoma.

Metabolic pattern reconstruction is an important factor in tumor progression. Metabolism of tumor cells is characterized by abnormal increase in anaerobic glycolysis, regardless of high oxygen concentration, resulting in a significant accumulation of energy from glucose sources. These changes promotes rapid cell proliferation and tumor growth, which is further referenced a process known as the Warburg effect. The current study reconstructed the metabolic pattern in progression of cancer to identify genetic changes specific in cancer cells. A total of 12 common types of solid tumors were included in the current study. Gene set enrichment analysis (GSEA) was performed to analyze 9 glycolysis-related gene sets, which are implicated in the glycolysis process. Univariate and multivariate analyses were used to identify independent prognostic variables for construction of a nomogram based on clinicopathological characteristics and a glycolysis-related gene prognostic index (GRGPI). The prognostic model based on glycolysis genes showed high area under the curve (AUC) in LIHC (Liver hepatocellular carcinoma). The findings of the current study showed that 8 genes (AURKA, CDK1, CENPA, DEPDC1, HMMR, KIF20A, PFKFB4, STMN1) were correlated with overall survival (OS) and recurrence-free survival (RFS). Further analysis showed that the prediction model accurately distinguished between high- and low-risk cancer patients among patients in different clusters in LIHC. A nomogram with a well-fitted calibration curve based on gene expression profiles and clinical characteristics showed good discrimination based on internal and external cohorts. These findings indicate that changes in expression level of metabolic genes implicated in glycolysis can contribute to reconstruction of tumor-related microenvironment.

Tumor mutation burden is correlated with response and prognosis in microsatellite-stable (MSS) gastric cancer patients undergoing neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NACT) before radical gastrectomy is preferred for locally advanced gastric cancer (GC). However, clinical practices demonstrate that a considerable proportion of GC patients do not benefit from NACT, largely due to the lack of biomarkers for patient selection and prognosis prediction. A recent study revealed that patients with microsatellite instability-high (MSI-H) may be resistant to NACT, however, most tumors in Chinese GC patients (~ 95%) are characterized by microsatellite stability (MSS). Here, we aimed to discover new molecular biomarkers for this larger population. METHODS: We performed whole-exome sequencing on 46 clinical samples (pre- and post-treatment) from 30 stage II/III MSS GC patients whose response to NACT was rigorously defined. Serum tumor markers (TMs), including AFP, CEA, CA199, CA724 and CA242 were measured during the course. RESULTS: High tumor mutation burden (TMB-H) and 19q12 amplification (19q12 +) were positively associated with the NACT response. When TMB and 19q12 amplification were jointly analyzed, those with TMB-H or 19q12 + showed favorable response to NACT (p = 0.035). Further, TMB-H was negatively correlated with ypN stage, lymph node metastasis, and macrophage infiltration. Patients with TMB-H showed better disease-free survival (DFS) than those with TMB-L (P = 0.025, HR = 0.1331), and this was further validated using two larger GC datasets: TCGA-STAD (p = 0.004) and ICGC-CN (p = 0.045). CONCLUSION: The combination of TMB-H and 19q12 + can serve as an early indicator of response to NACT. Superior to traditional clinical indicators, TMB-H is a robust and easily accessible candidate biomarker associated with better DFS, and can be evaluated at the time of diagnosis.

Five-gene signature associating with Gleason score serve as novel biomarkers for identifying early recurring events and contributing to early diagnosis for Prostate Adenocarcinoma.

Background: Compared to non-recurrent type, recurrent prostate adenocarcinoma (PCa) is highly fatal, and significantly shortens the survival time of affected patients. Early and accurate laboratory diagnosis is particularly important in identifying patients at high risk of recurrence, necessary for additional systemic intervention. We aimed to develop efficient and accurate diagnostic and prognostic biomarkers for new PCa following radical therapy. Methods: We identified differentially expressed genes (DEGs) and clinicopathological data of PCa patients from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) repositories. We then uncovered the most relevant clinical traits and genes modules associated with PCa prognosis using the Weighted gene correlation network analysis (WGCNA). Univariate Cox regression analysis and multivariate Cox proportional hazards (Cox-PH) models were performed to identify candidate gene signatures related to Disease-Free Interval (DFI). Data for internal and external cohorts were utilized to test and validate the accuracy and clinical utility of the prognostic models. Results: We constructed and validated an accurate and reliable model for predicting the prognosis of PCa using 5 Gleason score-associated gene signatures (ZNF695, CENPA, TROAP, BIRC5 and KIF20A). The ROC and Kaplan-Meier analysis revealed the model was highly accurate in diagnosing and predicting the recurrence and metastases of PCa. The accuracy of the model was validated using the calibration curves based on internal TCGA cohort and external GEO cohort. Using the model, patients could be prognostically stratified in to various groups including TNM classification and Gleason score. Multivariate analysis revealed the model could independently predict the prognosis of PCa patients and its utility was superior to that of clinicopathological characteristics. In addition, we fund the expression of the 5 gene signatures strongly and positively correlated with tumor purity but negatively correlated with infiltration CD8+ T cells to the tumor microenvironment. Conclusions: A 5 gene signatures can accurately be used in the diagnosis and prediction of PCa prognosis. Thus this can guide the treatment and management prostate adenocarcinoma.

Case Report: Next-Generation Sequencing Reveals Tumor Origin in a Female Patient With Brain Metastases.

BACKGROUND: Brain metastasis mainly originates from lung cancer. Napsin A and TTF-1 factors have frequently been detected in lung adenocarcinoma cases. Brain metastasis tumors with napsin A and TTF-1 positive are easily classified as lung adenocarcinoma origin. However, some thyroid cancers also exhibit these clinical features. Besides, lung is the most common metastasis of undifferential thyroid cancer. Therefore, it requires development of novel diagnostic tools to aid in distinguishing between pulmonary and thyroid origin. PATIENT FINDINGS: We reported a case that was initially diagnosed as brain metastatic lung cancer based on immunohistochemistry results. Analysis of next-generation sequencing (NGS) data from the brain lesion revealed that the cancer may have originated from the thyroid. We detected combo mutations in TERT promoter mutation, RET fusion and TP53, which are common in undifferential thyroid cancer (UTC), but rare for lung cancer. These results, coupled with identification of PAX8, indicated that this patient had UTC. Additionally, her three sons, despite being asymptomatic, were all diagnosed with papillary thyroid carcinoma. SUMMARY: The patient received anlotinib treatment and showed good clinical outcomes. One month after anlotinib treatment, the pulmonary nodules were found to be controlled, and the thyroid tumor drastically reduced, and tracheal compression relieved. She continued anlotinib treatment for the following two months, but died one month later because the treatment stopped owing to financial reasons. All her sons underwent total thyroidectomy with lymph node dissection. CONCLUSIONS: Although NGS has been reported to assist in diagnosis of the origin of some tumors, this is the first evidence of NGS for the determination of the origin of thyroid tumors. To our knowledge, this is the first time that a combination of multiple mutations has been used to help determine the origin of a tumor, compared with the previous single mutant gene. Moreover, this is the first evidence on the use of anlotinib for treatment of UTC with distant metastasis. Besides, all three sons of the patient had thyroid carcinoma in subsequent examinations, indicating high-risk for familial non-medullary thyroid cancer in UTC patients and necessity for performing thyroid ultrasound testing in other family members.

Emerging roles and mechanisms of microRNA­222­3p in human cancer (Review).

MicroRNAs (miRNAs/miRs) are a class of small non­coding RNAs that maintain the precise balance of various physiological processes through regulating the function of target mRNAs. Dysregulation of miRNAs is closely associated with various types of human cancer. miR­222­3p is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in tumor occurrence and progression. miR­222­3p in human biofluids, such as urine and plasma, may be a potential biomarker for the early diagnosis of tumors. In addition, miR­222­3p acts as a prognostic factor for the survival of patients with cancer. The present review first summarizes and discusses the role of miR­222­3p as a biomarker for diverse types of cancers, and then focuses on its essential roles in tumorigenesis, progression, metastasis and chemoresistance. Finally, the current understanding of the regulatory mechanisms of miR­222­3p at the molecular level are summarized. Overall, the current evidence highlights the crucial role of miR­222­3p in cancer diagnosis, prognosis and treatment.

Association between dietary sodium, potassium intake and lung cancer risk: evidence from the prostate, lung, colorectal and ovarian cancer screening trial and the Women's Health Initiative.

BACKGROUND: Epidemiological studies have reported that dietary mineral intake plays an important role on lung cancer risk, but the association of sodium, potassium intake is still unclear. METHODS: We determined the association between dietary sodium, potassium intake and lung cancer risk based on the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial and the Women's Health Initiative (WHI). Totally 165,409 participants who completed the baseline questionnaire (BQ) and diet history questionnaire (DHQ) were included into the analytical dataset, including 92,984 (44,959 men and 48,025 women) from the PLCO trial and 72,425 (women only) from the WHI cohort. Multivariable Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident lung cancer associated with dietary potassium and sodium intake. The dose-response relationship was also described using the spline smoothed curve after adjusting covariates. RESULTS: After the median follow-up of 8.55 and 18.56 years, 1,278 and 1,631 new cases of lung cancer were identified in the PLCO trial and WHI cohort, respectively. Intake of sodium was significantly associated with the incidence of lung cancer in the PLCO trial after multivariate adjustment for men (HR: 1.19, 95% CI: 1.05-1.35; P for linear trend =0.044). There was a suggestion that lung cancer risk had a quadratic curve correlation with the increase of potassium intake for women (third vs. lowest quintile: HR: 0.72, 95% CI: 0.54-0.96; P for quadratic trend =0.042). The similar results showing an inverse association between potassium intake and lung cancer risk were also observed in the WHI cohort for women (highest vs. lowest quintile: HR: 0.82, 95% CI: 0.70-0.97; P for linear trend =0.009). CONCLUSIONS: Appropriate intake of potassium has a protective effect against lung cancer, while high consumption of sodium is associated with an increased risk of lung cancer.