Endoscopic detection and diagnosis of gastric cancer using image-enhanced endoscopy: A systematic review and meta-analysis.

Objectives: We aimed to conduct a systematic review and meta-analysis to assess the value of image-enhanced endoscopy including blue laser imaging (BLI), linked color imaging, narrow-band imaging (NBI), and texture and color enhancement imaging to detect and diagnose gastric cancer (GC) compared to that of white-light imaging (WLI). Methods: Studies meeting the inclusion criteria were identified through PubMed, Cochrane Library, and Japan Medical Abstracts Society databases searches. The pooled risk ratio for dichotomous variables was calculated using the random-effects model to assess the GC detection between WLI and image-enhanced endoscopy. A random-effects model was used to calculate the overall diagnostic performance of WLI and magnifying image-enhanced endoscopy for GC. Results: Sixteen studies met the inclusion criteria. The detection rate of GC was significantly improved in linked color imaging compared with that in WLI (risk ratio, 2.20; 95% confidence interval [CI], 1.39-3.25; p < 0.01) with mild heterogeneity. Magnifying endoscopy with NBI (ME-NBI) obtained a pooled sensitivity, specificity, and area under the summary receiver operating curve of 0.84 (95 % CI, 0.80-0.88), 0.96 (95 % CI, 0.94-0.97), and 0.92, respectively. Similarly, ME-BLI showed a pooled sensitivity, specificity, and area under the curve of 0.81 (95 % CI, 0.77-0.85), 0.85 (95 % CI, 0.82-0.88), and 0.95, respectively. The diagnostic efficacy of ME-NBI/BLI for GC was evidently high compared to that of WLI, However, significant heterogeneity among the NBI studies still existed. Conclusions: Our meta-analysis showed a high detection rate for linked color imaging and a high diagnostic performance of ME-NBI/BLI for GC compared to that with WLI.

The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Analysis of lens cloudiness during endoscopic submucosal dissection procedures: Effects of a novel lens cleaner.

Objectives: We aimed to identify independent factors for intraoperative endoscopic lens cloudiness during gastric and colorectal endoscopic submucosal dissections, investigate the effectiveness of Cleastay, an endoscope anti-fog solution, and examine factors associated with severe submucosal fat deposition. Methods: A total of 220 patients who underwent gastric or colorectal endoscopic submucosal dissections in two institutions between January 2022 and October 2023 were included. Significant factors related to cloudiness were determined using univariate and multivariate analyses. Patient background and tumor characteristics related to severe submucosal fat deposition were investigated, and the degree of intraoperative endoscopic lens cloudiness and outcomes were compared between the Cleash and Cleastay groups. Results: In the multivariate analysis, factors increasing lens cloudiness included long procedure time (odds ratio [OR], 17.51; 95% confidence interval [CI], 1.52-202.08), stomach (vs. colon; OR, 5.08; 95% CI, 1.99-12.96), and severe submucosal fat deposition (OR, 12.19; 95% CI, 5.02-29.60). Conversely, the use of Cleastay (vs. Cleash; OR, 0.066; 95% CI, 0.021-0.21) was identified as a factor reducing cloudiness. Location analysis revealed that severe submucosal fat deposition was more common in the upper stomach and right colon. Conclusions: It was suggested that Cleastay is more useful for endoscopic submucosal dissection of the upper stomach and right colon, where severe submucosal fat deposition is expected.

Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Immune killer cells treatment for previously treated stage IV NSCLC patients.

The 5-year survival is poor for stage IV non-small cell lung cancer (NSCLC). Recently, cell immunotherapy has emerged as a new treatment strategy. This study aimed to evaluate the efficacy and safety of Immune killer cells (IKC) in patients with stage IV NSCLC after the failure of prior chemotherapy. This study enrolled 26 patients with stage IV NSCLC who failed at least two lines of chemotherapy with or without targeted therapy. The IKC was given alone weekly for 24 weeks. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), pain intensity, quality of life (QOL), and safety. The median PFS for the intent-to-treat (ITT) population (i.e., all enrolled patients) was 3.8 month. In the per-protocol (PP) population (i.e., patients receiving > 12 IKC infusions), the median PFS was 5.6 months. Moreover, the ITT population showed a 1-year survival rate of 60.0%, while that for the PP population was 85.7%. Only 7 out of 200 AEs (3.5%) were related to the IKC infusion, and they were all rated as grade 1 in severity. The IKC infusion was well tolerated. This novel immunotherapy prolonged the PFS and improved the survival compared with historical data. It might be a potential treatment strategy for stage IV NSCLC patient who failed prior chemotherapy.ClinicalTrials.gov identifier: NCT03499834.

Clinical and molecular correlates of tumor aneuploidy in metastatic non-small cell lung cancer.

Recent studies have linked elevated tumor aneuploidy to anti-tumor immune suppression and adverse survival following immunotherapy. Herein, we provide supportive evidence for tumor aneuploidy as a biomarker of response to immunotherapy in patients with non-small cell lung cancer (NSCLC). We identify a dose-response relationship between aneuploidy score and patient outcomes. In two independent NSCLC cohorts (n = 659 patients), we demonstrate a novel association between elevated aneuploidy and non-smoking-associated oncogenic driver mutations. Lastly, we report enrichment of TERT amplification and immune-suppressive phenotypes of highly aneuploid NSCLC. Taken together, our findings emphasize a potentially critical role for tumor aneuploidy in guiding immunotherapy treatment strategies.

Potential utility of ADNP in circulating tumor cells as biomarker for prognostics in non-muscle-invasive bladder cancer.

This study aims to evaluate the prognostic utility of Activity-dependent neuroprotective protein (ADNP) expression in Circulating Tumor Cells (CTCs) inpatients with Non-muscle-invasive Bladder Cancer (NMIBC) undergoing Transurethral Resection of Bladder Tumor (TURBT). A prospective cohort of 74 bladder cancer patients and 22 non-cancer controls were enrolled. The expression of ADNP mRNA was detected by immunomagnetic beads-droplet digital PCR. The ADNP mRNA expression was evaluated in patients with high-risk NMIBC and those with indeterminate invasion depth post 2nd TURBT. Primary cultured bladder cancer cells and PBMCs from healthy donors were immunofluorescence stained. Our findings suggest that baseline ADNP mRNA level in CTCs shows potential as a prognostic marker for NMIBC with a sensitivity of 83.33% and a specificity of 73.58%. In comparison to baseline, ADNP mRNA expression increased post 2nd TURBT in 5 patients, where 2 experienced recurrence. Meanwhile, among the 12 patients with decreased levels, only one patient relapsed. A considerable limitation of this study entails the small sample size. The Immuno-magnetic beads-ddPCR technique provided a viable method for ADNP mRNA detection in CTCs from bladder cancer patients. The preoperative ADNP mRNA level in CTCs was identified as a prognostic indicator for NMIBC. Longitudinal monitoring of ADNP mRNA in CTCs of bladder cancer patients shows promise in evaluating treatment responses and predicting prognosis.

CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.

BACKGROUND: Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. METHODS: Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl-biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. RESULTS: We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. CONCLUSIONS: Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.

Modulation of PD-L1 by Astragalus polysaccharide attenuates the induction of melanoma stem cell properties and overcomes immune evasion.

BACKGROUND: Melanoma is a highly aggressive form of skin cancer. The existence of cancer stem cells (CSCs) and tumor immune evasion are two major causes of melanoma progression, but no effective treatment has been found at present. Astragalus polysaccharide (APS) is a principal active component derived from Astragalus membranaceus, showing anti-tumor effects in various tumors including melanoma. However, the underlying mechanism is still unclear. METHODS: The regulation of APS on self-renewal ability and CSC markers expression in melanoma stem cells (MSCs) was measured by tumor sphere formation and tumorigenicity assays, RT-qPCR, and western blot. Flow cytometry was conducted to evaluate the activation of immune system by APS in melanoma mice. Further, the mechanism was explored based on PD-L1 overexpression and knock-down B16 cells. RESULTS: APS attenuated the tumor sphere formation of MSCs in vitro as well as the tumorigenicity in vivo. It also decreased the expression of CD133, BMI1 and CD47. Based on the PD-L1 overexpression and knock-down B16 cells, it was confirmed that APS inhibited the induction of MSCs by down-regulating PD-L1 expression. Meanwhile, APS increased the infiltration of CD4+ and CD8+T cells in tumor tissues because of its inhibitory effect on PD-L1. CONCLUSIONS: APS inhibited MSC induction and overcame tumor immune evasion through reducing PD-L1 expression. This study provided compelling evidence that APS could be a prospective therapeutic agent for treating melanoma.

A predictive model for colorectal cancer complicated with intestinal obstruction based on specific inflammation score.

PURPOSE: Inflammatory factors play an important role in the onset and progression of colorectal cancer (CRC). This study aimed to develop and validate a novel scoring system that utilizes specific inflammatory factor indicators to predict intestinal obstruction in CRC patients. METHODS: This study conducted a retrospective analysis of 1,470 CRC patients who underwent surgical resection between January 2013 and July 2018. These patients were randomly allocated to the training group (n = 1060) and the validation group (n = 410). Univariate and multivariate logistic regression analyses were performed to identify independent predictive factors for intestinal obstruction. The CRC peculiar inflammation score (CPIS), comprising lymphocyte-to-monocyte ratio (LMR), prognostic nutrition index (PNI), and alanine transaminase-to-lymphocyte ratio index (ALRI) scores, was significantly associated with the occurrence of intestinal obstruction. A nomogram combining CPIS with other clinical features was developed to predict this occurrence. Model accuracy was assessed by determining the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: The CPIS generated by multi-factor logistic regression was as follows: - 1.576 × LMR - 0.067 × PNI + 0.018 × ALRI. Using CPIS cutoff values of 50% (- 7.188) and 85% (- 6.144), three predictive groups were established. Patients with a high CPIS had a significantly higher risk of intestinal obstruction than those with a low CPIS (odds ratio [OR]: 10.0, confidence interval [CI]: 5.85-17.08, P < 0.001). The predictive nomogram demonstrated good calibration and discrimination abilities. The AUC of the ROC curve for the obstruction nomogram was 0.813 (95% CI: 0.777-0.850) in the training set and 0.806 (95% CI: 0.752-0.860) in the validation set. The calibration curve exhibited neither bias nor high credibility. Decision curve analysis indicated the utility of this predictive model. CONCLUSION: CRC-associated intestinal obstruction is closely linked to inflammatory markers in patients. CPIS is a CRC-specific inflammatory predictive score based on a combination of inflammatory-related indicators. A high CPIS serves as a strong indicator of intestinal obstruction. Its integration with other clinical factors and preoperative inflammatory-specific indicators significantly enhances the diagnosis and treatment of CRC patients with intestinal obstruction.

Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer.

BACKGROUND: Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal. Previous studies have identified PA3264 as a possible active ingredient in Squama Manis. In this study, we systematically investigated the pharmacological effects and mechanisms of PA3264 in the treatment of triple-negative breast cancer (TNBC), a representative breast-related disease. METHODS: Cell viability and colony formation assays were performed after treatment with the target dipeptide PA3264 in vitro. Next, 4T1 orthotopic tumors and humanized PBMC-CDX mouse models were generated to examine the antitumor effect of PA3264 in vivo. Transcriptome sequencing and molecular docking experiments were performed to predict pathways to function. Western blotting and quantitative real-time PCR were used to validate the molecular mechanisms underlying the anticancer effects of PA3264. RESULTS: PA3264 significantly inhibited cell viability and migration of breast cancer cells in vitro. Furthermore, PA3264 suppressed the tumor size and reduced the tumor weight in vivo. Finally, it was verified that PA3264 prevented the progression of breast cancer by inhibiting the PI3K/AKT/NF-κB pathway, causing cell cycle arrest, and promoting apoptosis. CONCLUSIONS: This study elucidated that PA3264 derived from rare and endangered Squama Manis was a novel bioactive peptide for treating triple-negative breast cancer from a scientific research perspective.

MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population.

BACKGROUND: Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients. METHODS: This case-cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan-Meier and Cox proportional hazards model analyses. RESULTS: MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03-5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07-8.95, p = 0.037). CONCLUSIONS: This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care.

Diagnostic and prognostic significance of ALU-based cell-free DNA in colorectal cancer: a systematic review and meta-analysis.

Introduction: Colorectal cancer (CRC) is a major global health concern. This study aimed to investigate the role of ALU-based cell-free DNA (cfDNA) in the diagnosis and prognosis of CRC. Methods: We selected relevant literature from PubMed, Scopus, Web of Science, EMBASE, and Science Direct databases based on strict inclusion and exclusion criteria. 17 eligible studies were included in the final analysis (13 studies for diagnostic and 4 studies for prognostic meta-analysis). The search covered relevant publications up to July 1, 2024. Results: The pooled sensitivity, specificity, and diagnostic odds ratios (DOR) of ALU-based cfDNA in CRC diagnosis were 0.81 (95% CI= [0.70, 0.89]), 0.90 (95% CI= [0.70, 0.96]), and 40.58 (95% CI= [17.87, 92.19]), respectively. The area under the ROC curve was 0.92 (95% CI= [0.89, 0.94]). Patients with higher concentrations of plasma/serum ALU-based cfDNA had poorer overall survival (OS) (pooled hazard ratio = 2.33 ([95% CI= [1.80, 3.03]). Conclusion: The current evidence supports the utility of circulating ALU as a promising non-invasive diagnostic and prognostic tool for CRC. Furthermore, as a potential biomarker, ALU-based cfDNA could play a significant role in clinical application. Clinical implications: The evidence suggests that circulating ALU-based cell-free DNA (cfDNA) holds promise as a non-invasive diagnostic and prognostic tool for colorectal cancer, potentially enhancing clinical decision-making. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42023486369).

Single nucleotide variants in lung cancer.

Germline genetic variants, including single-nucleotide variants (SNVs) and copy number variants (CNVs), account for interpatient heterogeneity. In the past several decades, genome-wide association studies (GWAS) have identified multiple lung cancer-associated SNVs in Caucasian and Chinese populations. These variants either reside within coding regions and change the structure and function of cancer-related proteins or reside within non-coding regions and alter the expression level of cancer-related proteins. The variants can be used not only for cancer risk assessment and prevention but also for the development of new therapies. In this review, we discuss the lung cancer-associated SNVs identified to date, their contributions to lung tumorigenesis and prognosis, and their potential use in predicting prognosis and implementing therapeutic strategies.

From sequencing to validation: NGS-based exploration of plasma miRNA in papillary thyroid carcinoma.

Objective: A non-invasive method using plasma microRNAs provides new insights into thyroid cancer diagnosis. The objective of this study was to discover potential circulating biomarkers of papillary thyroid carcinoma (PTC) through the analysis of plasma miRNAs using next-generation sequencing (NGS). Methods: Plasma miRNAs were isolated from peripheral blood samples collected from healthy individuals, patients diagnosed with PTC, and those with benign thyroid nodules. The Illumina NovaSeq 6000 platform was employed to establish the miRNA expression profiles. Candidate miRNAs for diagnostic purposes were identified utilizing the Random Forest (RF) algorithm. The selected miRNAs were subsequently validated in an independent validation set using RT-qPCR. Results: NGS results revealed consistent plasma miRNA expression patterns among healthy individuals and patients with benign thyroid nodules in the discovery set (6 healthy cases, 17 benign cases), while differing significantly from those observed in the PTC group (17 PTC cases). Seven miRNAs exhibiting significant expression differences were identified and utilized to construct an RF classifier. Receiver operating characteristic (ROC) analysis for PTC diagnosis, and the area under the curve (AUC) was 0.978. Subsequent KEGG and GO analyses of the target genes associated with these 7 miRNAs highlighted pathways relevant to tumors and the cell cycle. Independent validation through RT-qPCR in a separate cohort (15 CONTROL, 15 PTC groups) underscored hsa-miR-301a-3p and hsa-miR-195-5p as promising candidates for PTC diagnosis. Conclusion: In conclusion, our study established a seven-miRNA panel in plasma by Random Forest algorithm with significant performance in discriminating PTC from healthy or benign group. hsa-miR-301a-3p, hsa-miR-195-5p in plasma have potential for further study in the diagnosis of PTC in Asian ethnic.

Understanding cachexia and its impact on lung cancer and beyond.

Cancer cachexia is a multifactorial syndrome characterized by loss of body weight secondary to skeletal muscle atrophy and adipose tissue wasting. It not only has a significant impact on patients' quality of life but also reduces the effectiveness and tolerability of anticancer therapy, leading to poor clinical outcomes. Lung cancer is a prominent global health concern, and the prevalence of cachexia is high among patients with lung cancer. In this review, we integrate findings from studies of lung cancer and other types of cancer to provide an overview of recent advances in cancer cachexia. Our focus includes topics such as the clinical criteria for diagnosis and staging, the function and mechanism of selected mediators, and potential therapeutic strategies for clinical application. A comprehensive summary of current studies will improve our understanding of the mechanisms underlying cachexia and contribute to the identification of high-risk patients, the development of effective treatment strategies, and the design of appropriate therapeutic regimens for patients at different disease stages.

Resolution of occult anastomotic stricture with anal dilator: challenges with the conventional diagnostic criteria in low anterior rectal resection patient-a case report.

Background: Anastomotic stricture (AS) is a common complication following rectal cancer surgery with anastomosis, but its diagnosis and management pose significant challenges due to the lack of standardized diagnostic criteria. We present a case highlighting the complexities encountered in diagnosing and managing occult AS post-rectal cancer surgery. Case presentation: A 51-year-old male patient presented with symptoms suggestive of AS following robot-assisted laparoscopic low anterior resection for rectal adenocarcinoma. Despite conventional evaluations, including colonoscopy, digital rectal examination, and radiography, AS was not identified. Following prolonged and ineffective treatment for suspected conditions such as low anterior resection syndrome (LARS), the patient underwent anal dilatation, resulting in significant symptom improvement. Conclusions: This case underscores the challenges associated with diagnosing and managing occult AS following rectal cancer surgery. The absence of standardized diagnostic criteria and reliance on conventional modalities may lead to underdiagnosis and inadequate treatment. A comprehensive diagnostic approach considering intestinal diameter, elasticity, and symptoms related to difficult defecation may enhance diagnostic accuracy. Further research is needed to refine the diagnostic and therapeutic strategies for occult AS.

Association of US county-level social vulnerability index with breast, colorectal, and lung cancer screening, incidence, and mortality rates across US counties.

Background: Despite being the second leading cause of death in the United States, cancer disproportionately affects underserved communities due to multiple social factors like economic instability and limited healthcare access, leading to worse survival outcomes. This cross-sectional database study involves real-world data to explore the relationship between the Social Vulnerability Index (SVI), a measure of community resilience to disasters, and disparities in screening, incidence, and mortality rates of breast, colorectal, and lung cancer. The SVI encompasses four themes: socioeconomic status, household composition & disability, minority status & language, and housing type & transportation. Materials and methods: Using county-level data, this study compared cancer metrics in U.S. counties and the impact of high and low SVI. Two-sided statistical analysis was performed to compare SVI tertiles and cancer screening, incidence, and mortality rates. The outcomes were analyzed with logistic regression to determine the odds ratio of SVI counties having cancer metrics at or above the median. Results: Our study encompassed 3,132 United States counties. From publicly available SVI data, we demonstrated that high SVI scores correlate with low breast and colorectal cancer screening rates, along with high incidence and mortality rates for all three types of cancers. County level SVI has impact on incidence rates of cancers; breast cancer rates were lowest in high SVI counties, while colorectal and lung cancer rates were highest in the same counties. Age-adjusted mortality rates for all three cancers increased across SVI tertiles. After risk adjustment, a 10-point SVI increase correlated with lower screening and higher mortality rates. Conclusion: In conclusion, our study establishes a significant correlation between SVI and cancer metrics, highlighting the potential to identify marginalized communities with health disparities for targeted healthcare initiatives. It underscores the need for further longitudinal studies on bridging the gap in overall cancer care in the United States.

The mechanism of ITGB4 in tumor migration and invasion.

Integrin ß4 (ITGB4) is a transmembrane protein that functions as a mechanosensor, mediating the bidirectional exchange of information between the intracellular and extracellular matrices. ITGB4 plays a critical role in cell adhesion, migration, and signaling. Numerous studies have implicated ITGB4 as a key facilitator of tumor migration and invasion. This review provides a foundational description of the mechanisms by which ITGB4 regulates tumor migration and invasion through pathways involving focal adhesion kinase (FAK), protein kinase B (AKT), and matrix metalloproteinases (MMPs). These mechanisms encompass epithelial-mesenchymal transition (EMT), phosphorylation, and methylation of associated molecules. Additionally, this review explores the role of ITGB4 in the migration and invasion of prevalent clinical tumors, including those of the digestive system, breast, and prostate.