Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

ST8SIA6-AS1, a novel lncRNA star in liver cancer.

Liver cancer is one of the most lethal gastrointestinal malignancies. Emerging evidence has underscored the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with ST8SIA6-AS1 identified as a novel oncogenic lncRNA contributing to liver cancer progression. ST8SIA6-AS1 is consistently upregulated in hepatic cancer tissues and is strongly associated with unfavorable prognosis. Moreover, it demonstrates high diagnostic efficacy in detecting HCC. ST8SIA6-AS1 is involved in various cellular processes including proliferation, migration, and invasion, primarily through its function as a competing endogenous RNA (ceRNA), thereby facilitating hepatocarcinogenesis and disease advancement. This review provides a detailed examination of the molecular functions and regulatory mechanisms of ST8SIA6-AS1 in hepatocellular carcinoma (HCC) and highlights its potential as a promising biomarker for liver cancer, aiming to propel the development of innovative therapeutic strategies for HCC management.

Adipocytes impact on gastric cancer progression: Prognostic insights and molecular features.

BACKGROUND: Adipocytes, especially adipocytes within tumor tissue known as cancer-associated adipocytes, have been increasingly recognized for their pivotal role in the tumor microenvironment of gastric cancer (GC). Their influence on tumor progression and patient prognosis has sparked significant interest in recent research. The main objectives of this study were to investigate adipocyte infiltration, assess its correlation with clinical pathological features, develop a prognostic prediction model based on independent prognostic factors, evaluate the impact of adipocytes on immune cell infiltration and tumor invasiveness in GC, and identify and validate genes associated with high adipocyte expression, exploring their potential diagnostic and prognostic value. AIM: To explore the relationship between increased adipocytes within tumor tissue and prognosis in GC patients as well as the associated mechanisms and potential biomarkers, using public databases and clinical data. METHODS: Using mRNA microarray datasets from the Gene Expression Omnibus database and clinical samples from Jiangsu Provincial Hospital, survival and regression analyses were conducted to determine the relevant prognostic factors in GC. Feature gene selection was performed using least absolute shrinkage and selection operator and support vector machine recursive feature elimination algorithms, followed by differential gene expression analysis, gene ontology, pathway analysis, and Gene Set Enrichment Analysis. Immune cell infiltration was analyzed using the CIBERSORT algorithm. RESULTS: Tumor adipocyte infiltration correlated with poor prognosis in GC, leading to the development of a highly accurate and discriminative prognostic prediction model. Key genes, ADH1B, SFRP1, PLAC9, and FABP4, were identified as associated with high adipocyte expression in GC. The diagnostic and prognostic potential of these identified genes was validated using independent datasets. Downregulation of immune cells was observed in GC with high adipocyte expression. CONCLUSION: GC with high intratumoral adipocyte expression demonstrated aggressive tumor biology and a poorer prognosis. The genes ADH1B, SFRP1, PLAC9, and FABP4 have been identified as holding diagnostic and prognostic significance in GC. These findings strongly support the use of adipocyte expression as a valuable indicator of tumor invasiveness and anticipated patient outcomes in GC.

Paraoxonase-2 shRNA-mediated gene silencing suppresses proliferation and migration, while promotes chemosensitivity in clear cell renal cell carcinoma cell lines.

Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo- and radiotherapy and because of one-third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase-2 (PON2), an intracellular membrane-bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC.

MicroRNA-875-5p inhibits the growth and metastasis of cervical cancer cells by promoting autophagy and apoptosis and inhibiting the epithelial-mesenchymal transition.

Introduction: MicroRNA-875-5p (miR-875-5p) is a cancer-related microRNA. It has been demonstrated that miR-875-5p participates in the development of various types of cancer such as hepatocellular carcinoma, gastric carcinoma, prostate and bladder cancer. Previous research suggested that miR-875 is implicated in the development of cervical cancer cells. However, the exact role and function of miR-875-5p in cervical cancer remain unexplored. It is important to examine the role and function of miR-875-5p and the associated signaling pathway, as the findings may have diagnostic and therapeutic significance. Thus, in this study, we investigated the effect of miR-875-5p on the growth and metastasis of cervical cancer cells and the possible underlying mechanisms. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-875-5p in cervical cancer cells and normal cervical epithelium. After overexpression or co-expression of miR-875-5p in cells, the changes in cell function were analyzed. Western blot was used to detect the expression changes of epithelial-mesenchymal transition (EMT) -related proteins and autophagy-related proteins. Results: Functional studies demonstrated that miR-875-5p overexpression significantly inhibited the proliferation, migration, invasion, and EMT, and promotes apoptosis and autophagy of cervical cancer cells., while miR-875-5p knockdown promoted the proliferation, migration, invasion, and EMT, and inhibited apoptosis and autophagy cervical cancer cells. Furthermore, Western blot results showed that overexpression of miR-875-5p downregulated the expressions of N-cadherin, Snail, Vimentin and microtubule-associated protein 1 light chain 3B I (LC3B I). Conversely, miR-875-5p upregulated the expression of E-cadherin. Conclusion: In conclusion, our findings suggest that miR-875-5p functions as a tumor inhibitor suppressing the growth and metastasis of cervical cancer. Overexpression of miR-875-5p inhibits malignant behavior and promotes autophagy and apoptosis in cervical cancer cells. These findings advance our understanding of the role and function of miR-875-5p in cervical cancer and could facilitate the development of early genetic markers or biomarkers and therapeutic targets for cervical cancer.

In situ generated CdTe quantum dot-encapsulated hafnium polymer membrane to boost electrochemiluminescence analysis of tumor biomarkers.

Exploring the construction of an interface with bright emission, fabulous stability, and good function to develop high-performance electrochemiluminescence (ECL) biosensors for tumor biomarkers is in high demand but faces a huge challenge. Herein, we report an oriented attachment and in situ self-assembling strategy for one-step fabrication of CdTe QD-encapsulated Hf polymer membrane onto an ITO surface (Hf-CP/CdTe QDs/APS/ITO). Hf-CP/CdTe QDs/APS/ITO is fascinating with excellent stability, high ECL emission, and specific adsorption toward ssDNA against dsDNA and mononucleotides (mNs). These interesting properties make it an ideal interface to rationally develop an immobilization-free ECL biosensor for cancer antigen 125 (CA125), used as a proof-of-concept analyte, based on target-aptamer recognition-promoted exonuclease III (Exo III)-assisted digestion. The recognition of ON by CA125 leads to the formation of CA125@ON, which hybridizes with Fc-ssDNA to switch Exo III-assisted digestion, decreasing the amount of Fc groups anchored onto the electrode's surface and blocking electron transfer. As compared to the case where CA125 was absent, significant ECL emission recovery is determined and relies on CA125 concentration. Thus, highly sensitive analysis of CA125 against other biomarkers was achieved with a limit of detection down to 2.57 pg/mL. We envision this work will provide a new path to develop ECL biosensors with excellent properties, which shows great potential for early and accurate diagnosis of cancer.

Circulating tumor DNA for predicting recurrence in patients with operable breast cancer: a systematic review and meta-analysis.

BACKGROUND: The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC. MATERIALS AND METHODS: A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed. RESULTS: Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months). CONCLUSIONS: ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.

LINC01134: a pivotal oncogene with promising predictive maker and therapeutic target in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a leading and fatal malignancy within the gastrointestinal tract. Recent advancements highlight the pivotal role of long non-coding RNAs (lncRNAs) in diverse biological pathways and pathologies, particularly in tumorigenesis. LINC01134, a particular lncRNA, has attracted considerable attention due to its oncogenic potential in hepatoma. Current research underscores LINC01134's potential in augmenting the onset and progression of HCC, with notable implications in drug resistance. This review comprehensively explores the molecular functions and regulatory mechanisms of LINC01134 in HCC, offering a fresh perspective for therapeutic interventions. By delving into LINC01134's multifaceted roles, we aim to foster novel strategies in HCC management.

[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

Metagenomic analysis of fecal samples in colorectal cancer Egyptians patients post colectomy: A pilot study.

One of the most prevalent malignancies that significantly affects world health is colorectal cancer (CRC). While genetics are involved in a portion of CRC patients, most cases are sporadic. The microbiome composition could be a new source of tumor initiation and progression. This research was conducted to investigate the microbiota composition of CRC patients post colectomy at taxonomic and functional levels. Using a next-generation sequencing approach, using an Illumina Novaseq 6000, the fecal samples of 13 patients were analyzed and the obtained data was subjected to a bioinformatics analysis. The bacterial abundance and uniqueness varied in CRC patients alongside differences in bacterial counts between patients. Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, and Fusobacterium nucleatum were among the pro-cancerous microorganisms found. Concurrently, bacteria linked to CRC progression were detected that have been previously linked to metastasis and recurrence. At the same time, probiotic bacteria such as Bifidobacterium dentium, Bifidobacterium bifidum, and Akkermansia muciniphila increased in abundance after colectomies. Additionally, numerous pathways were deferentially enriched in CRC, which emerged from functional pathways based on bacterial shotgun data. CRC-specific microbiome signatures include an altered bacterial composition. Our research showed that microbial biomarkers could be more usefully employed to explore the link between gut microbiota and CRC using metagenomic techniques in the diagnosis, prognosis, and remission of CRC, thereby opening new avenues for CRC treatment.

Implementable assay for monitoring minimum residual disease after radical treatment for colorectal cancer.

Considering the cost and invasiveness of monitoring postoperative minimal residual disease (MRD) of colorectal cancer (CRC) after adjuvant chemoradiotherapy (ACT), we developed a favorable approach based on methylated circulating tumor DNA to detect MRD after radical resection. Analyzing the public database, we identified the methylated promoter regions of the genes FGD5, GPC6, and MSC. Using digital polymerase chain reaction (dPCR), we termed the "amplicon of methylated sites using a specific enzyme" assay as "AMUSE." We examined 180 and 114 pre- and postoperative serial plasma samples from 28 recurrent and 19 recurrence-free pathological stage III CRC patients, respectively. The results showed 22 AMUSE-positive of 28 recurrent patients (sensitivity, 78.6%) and 17 AMUSE-negative of 19 recurrence-free patients (specificity, 89.5%). AMUSE predicted recurrence 208 days before conventional diagnosis using radiological imaging. Regarding ACT evaluation by the reactive response, 19 AMUSE-positive patients during their second or third blood samples showed a significantly poorer prognosis than the other patients (p = 9E-04). The AMUSE assay stratified four groups by the altered patterns of tumor burden postoperatively. Interestingly, only 34.8% of cases tested AMUSE-negative during ACT treatment, indicating eligibility for ACT. The AMUSE assay addresses the clinical need for accurate MRD monitoring with universal applicability, minimal invasiveness, and cost-effectiveness, thereby enabling the timely detection of recurrences. This assay can effectively evaluate the efficacy of ACT in patients with stage III CRC following curative resection. Our study strongly recommends reevaluating the clinical application of ACT using the AMUSE assay.

Contribution of the Paraoxonase-2 Enzyme to Cancer Cell Metabolism and Phenotypes.

Paraoxonase-2 (PON2) is a ubiquitously expressed intracellular protein that is localized in the perinuclear region, the endoplasmic reticulum (ER), and mitochondria, and is also associated with the plasma membrane. PON2 functions as an antioxidant enzyme by reducing the levels of reactive oxygen species (ROS) in the mitochondria and ER through different mechanisms, thus having an anti-apoptotic effect and preventing the formation of atherosclerotic lesions. While the antiatherogenic role played by this enzyme has been extensively explored within endothelial cells in association with vascular disorders, in the last decade, great efforts have been made to clarify its potential involvement in both blood and solid tumors, where PON2 was reported to be overexpressed. This review aims to deeply and carefully examine the contribution of this enzyme to different aspects of tumor cells by promoting the initiation, progression, and spread of neoplasms.

DARS-AS1: A Vital Oncogenic LncRNA Regulator with Potential for Cancer Prognosis and Therapy.

DARS-AS1, short for Aspartyl-tRNA synthetase antisense RNA 1, has emerged as a pivotal player in cancers. Upregulation of this lncRNA is a recurrent phenomenon observed across various cancer types, where it predominantly assumes oncogenic roles, exerting influence on multiple facets of tumor cell biology. This aberrant expression of DARS-AS1 has triggered extensive research investigations, aiming to unravel its roles and clinical values in cancer. In this review, we elucidate the significant correlation between dysregulated DARS-AS1 expression and adverse survival prognoses in cancer patients, drawing from existing literature and pan-cancer analyses from The Cancer Genome Atlas (TCGA). Additionally, we provide comprehensive insights into the diverse functions of DARS-AS1 in various cancers. Our review encompasses the elucidation of the molecular mechanisms, ceRNA networks, functional mediators, and signaling pathways, as well as its involvement in therapy resistance, coupled with the latest advancements in DARS-AS1-related cancer research. These recent updates enrich our comprehensive comprehension of the pivotal role played by DARS-AS1 in cancer, thereby paving the way for future applications of DARS-AS1-targeted strategies in tumor prognosis evaluation and therapeutic interventions. This review furnishes valuable insights to advance the ongoing efforts in combating cancer effectively.

A novel sphingolipid metabolism-related long noncoding RNA signature predicts the prognosis, immune landscape and therapeutic response in pancreatic adenocarcinoma.

Sphingolipid metabolism affects prognosis and resistance to immunotherapy in patients with cancer and is an emerging target in cancer therapy with promising diagnostic and prognostic value. Long noncoding ribonucleic acids (lncRNAs) broadly regulate tumour-associated metabolic reprogramming. However, the potential of sphingolipid metabolism-related lncRNAs in pancreatic adenocarcinoma (PAAD) is poorly understood. In this study, coexpression algorithms were employed to identify sphingolipid metabolism-related lncRNAs. The least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a sphingolipid metabolism-related lncRNA signature (SMLs). The prognostic predictive stability of the SMLs was validated using Kaplan-Meier. Univariate and multivariate Cox, receiver operating characteristic (ROC) and clinical stratification analyses were used to comprehensively assess the SMLs. Gene set variation analysis (GSVE), gene ontology (GO) and tumor mutation burden (TMB) analysis explored the potential mechanisms. Additionally, single sample gene set enrichment analysis (ssGSEA), ESTIMATE, immune checkpoints and drug sensitivity analysis were used to investigate the potential predictive function of the SMLs. Finally, an SMLs-based consensus clustering algorithm was utilized to differentiate patients and determine the suitable population for immunotherapy. The results showed that the SMLs consists of seven sphingolipid metabolism-related lncRNAs, which can well determine the clinical outcome of individuals with PAAD, with high stability and general applicability. In addition, the SMLs-based consensus clustering algorithm divided the TCGA-PAAD cohort into two clusters, with Cluster 1 showing better survival than Cluster 2. Additionally, Cluster 1 had a higher level of immune cell infiltration than Cluster 2, which combined with the higher levels of immune checkpoints in Cluster 1 suggests that Cluster 1 is more consistent with an immune 'hot tumor' profile and may respond better to immune checkpoint inhibitors (ICIs). This study offers new insights regarding the potential role of sphingolipid metabolism-related lncRNAs as biomarkers in PAAD. The constructed SMLs and the SMLs-based clustering are valuable tools for predicting clinical outcomes in PAAD and provide a basis for clinical selection of individualized treatments.

Hsa_circ_0014606 Derived from Exosomes Promotes Gastric Carcinoma Tumorigenesis and Proliferation by Sponging miR-514b-3p to Upregulate HNRNPC.

Gastric cancer is a common malignant tumor, and due to its insidious onset and limited screening methods, most patients are diagnosed with advanced disease and have a poor prognosis. The circRNA in exosomes has an essential role in cancer diagnosis and treatment. However, the part of hsa_circ_0014606 within exosomes in gastric cancer progression is unclear. Firstly, we extracted exosomes from the serum of gastric cancer patients and healthy individuals by ultracentrifugation and analyzed the expression of hsa_circ_0014606 in both exosomes; then knocked down hsa_circ_0014606 in vivo and in vitro, respectively, to observe its effect on the physiological function of gastric cancer cells; finally, we used bioinformatics to screen hsa_circ_0014606 targeting miRNAs and mRNAs, and experiments were performed to verify the interrelationship between the three. The results showed that the level of hsa_circ_0014606 in the serum exosomes of gastric cancer patients was significantly higher than that of the healthy population. The knockdown of hsa_circ_0014606 slowed the proliferation of gastric cancer cells, significantly reduced migration and invasion ability, accelerated apoptosis, and reduced tumor size in mice. In addition, the expression of hsa_circ_0014606 was negatively correlated with the expression of miR-514b-3p and positively correlated with the expression of heterogeneous nuclear ribonucleoprotein C (HNRNPC). In conclusion, hsa_circ_0014606 exerted a pro-cancer effect indirectly through miR-514b-3p targeting gene HNRNPC, and this study provides a new potential target for treating gastric cancer.

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

Clinical significance of baseline Epstein-Barr virus DNA for recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma.

Background: This study aimed to evaluate the clinical significance of baseline Epstein-Barr virus (EBV) DNA in recurrent or metastatic primary pulmonary lymphoepithelioma-like carcinoma (PLELC). Methods: 75 patients with baseline EBV DNA were included. The relationships between baseline EBV DNA and clinical characteristics, survival and objective response rate were analyzed. Results: The baseline EBV DNA levels were related to the liver, chest wall, distant lymph node(s) or multiple sites of distant metastasis. The high baseline EBV DNA group (≥41,900 copies/ml) was related to shorter progression-free and overall survival in univariate analysis and remained significant for progression-free survival in multivariate analysis. Conclusion: The baseline EBV DNA is a valuable biomarker for predicting prognosis and reflecting tumor burden in recurrent or metastatic PLELC.

Tumor Suppressor LncRNA on Chromosome 8p12 (TSLNC8): A Concise Review in Human Malignancies.

Tumor Suppressor Long Non-Coding RNA on Chromosome 8p12 (TSLNC8) is an RNA gene that generates a long non-coding RNA transcribed intergenically from both strands. Its significant role in human malignancies attracted significant attention in recent years. Expression analysis of TSLNC8 has been conducted in tissue specimens and cell lines using various techniques, including reverse transcription-quantitative polymerase chain reaction (RT-qPCR), in situ hybridization (ISH), and microarray analysis. Furthermore, functional studies involving the loss and/or gain of TSLNC8 function in cellular and animal models have been carried out. These investigations have highlighted the impact of TSLNC8 on key tumor-related processes, including migration, invasion, and metastasis. Moreover, TSLNC8 has emerged as a regulator capable of modulating critical signaling pathways, such as the Hippo, STAT3, WNT/ß-catenin, and MAPK pathways. In this review, we comprehensively synthesize the findings derived from in vitro and in vivo studies, along with analyses conducted on clinical samples, to provide a comprehensive understanding of the multifaceted role of TSLNC8 as a promising tumor biomarker and a potential target for therapeutic interventions.

Fecal microbial biomarkers combined with multi-target stool DNA test improve diagnostic accuracy for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a major global health burden. The current diagnostic tests have shortcomings of being invasive and low accuracy. AIM: To explore the combination of intestinal microbiome composition and multi-target stool DNA (MT-sDNA) test in the diagnosis of CRC. METHODS: We assessed the performance of the MT-sDNA test based on a hospital clinical trial. The intestinal microbiota was tested using 16S rRNA gene sequencing. This case-control study enrolled 54 CRC patients and 51 healthy controls. We identified biomarkers of bacterial structure, analyzed the relationship between different tumor markers and the relative abundance of related flora components, and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size, redundancy analysis, and random forest analysis. RESULTS: MT-sDNA was associated with Bacteroides. MT-sDNA and carcinoembryonic antigen (CEA) were positively correlated with the existence of Parabacteroides, and alpha-fetoprotein (AFP) was positively associated with Faecalibacterium and Megamonas. In the random forest model, the existence of Streptococcus, Escherichia, Chitinophaga, Parasutterella, Lachnospira, and Romboutsia can distinguish CRC from health controls. The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%, with a sensitivity and specificity of 98.1% and 92.3%, respectively. CONCLUSION: There is a positive correlation of MT-sDNA, CEA, and AFP with intestinal microbiome. Eight biomarkers including six genera of gut microbiota, MT-sDNA, and CEA showed a prominent sensitivity and specificity for CRC prediction, which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.

Prechemotherapy Not Preorchiectomy Serum Tumor Markers Accurately Identify International Germ Cell Cancer Collaborative Group Prognostic Groups in Nonseminoma.

Levels of the serum tumor markers (STMs) α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are used in staging classification for metastatic germ-cell cancers and support decisions on the intensity of first-line treatment for patients with nonseminoma. Use of preorchiectomy instead of prechemotherapy STM levels can lead to inadequate classification. We identified 744 men with metastatic gonadal nonseminoma in the International Germ-Cell Cancer Collaborative Group (IGCCCG) Update Consortium database who had preorchiectomy and prechemotherapy STM levels available. Of these, 22% would have had inadequate IGCCCG prognostic group classification if preorchiectomy levels had been used, which would have resulted in overtreatment of 16% and undertreatment of 6% of men. These findings suggest that use of preorchiectomy instead of prechemotherapy STM results may lead to incorrect IGCCCG classification, which could compromise treatment success or expose patients to unnecessary toxicity. Patient summary: For men with testicular cancer, levels of tumor markers in their blood are used when making decisions on chemotherapy intensity. Use of test results for samples taken before removal of the cancer-bearing testicle instead of immediately before chemotherapy can lead to inadequate treatment recommendations.