Ultrasensitive immunosensor for multiplex detection of cancer biomarkers carcinoembryonic antigen (CEA) and yamaguchi sarcoma viral oncogene homolog 1 (YES1) based on eco-friendly synthesized gold nanoparticles.

Cancer is one of the most extensive diseases with the highest mortality rate, accounting for almost 10 million deaths in 2020. The most common cancers are breast, lung, colon and rectum and prostate cancers. Of these, lung cancer, accounted for about 1.8 million of all cancer deaths (25%) in 2020. Detection of cancer relies on presence of biomarkers such as DNA molecules, proteins and metabolites released by cancerous cells into the circulation. Carcinoembryonic antigen (CEA) is one of the biomarkers that has been used for the detection of lung cancer. However, CEA is not specific to lung cancer since it is also manifested in gastric cancer, pancreatic cancer, colorectal cancer, and breast cancer. Recently, v-YES1 Yamaguchi sarcoma viral oncogene homolog 1 (YES1) was described as a specific biomarker for lung cancer. The detection of both CEA and YES1 would give more precise and authentic information for detecting lung cancer. This is because detection of a single tumor marker usually limits the precision in tumor diagnosis, due to the fact that several cancers have more than one marker linked with their prevalence. Whereas traditional methods have been used for the detection of CEA, electrochemical immunosensors have attracted considerable attention owing to their profound advantages, including fast response, miniaturization, high selectivity, low sample requirements and magnificent sensitivity. The fabrication of a multiplex and simultaneous immunosensor is met with challenge of preparation of distinguishable immunoprobes with different redox activities. This can be addressed by incorporation of electroactive Nano metals into the sensing platform. In this study, gold nanoparticles were used for the fabrication of an ultrasensitive sandwich electrochemical multiplex immunosensor for simultaneous detection of CEA and YES1. Under optimized conditions, the electrochemical immunosensor detection limit for YES1 and CEA was found to be 0.0022 and 0.0034 ng/mL respectively within a linear range of 0.1-50 ng/mL. The proposed immunosensor proved to be stable for up to 2 weeks and had negligible cross reactivity towards various interfering compounds in human plasma. This study reports that gold nanoparticles can be bio synthesized using shade dried Mangifera indica leaves extract. The bio-synthesized gold nanoparticles coupled with thiolated protein G can be used for fabrication of a multiplex immunosensor for detection of CEA and YES1. The proposed immunosensor can provide a new approach for early diagnosis of circulating cancer biomarkers and holds great promise for application in clinical diagnosis.

Antifouling modification for high-performance isolation of circulating tumor cells.

Circulating tumor cells (CTCs), which shed from solid tumor tissue into blood circulatory system, have attracted wide attention as a biomarker in the early diagnosis and prognosis of cancer. Given their potential significance in clinics, many platforms have been developed to separate CTCs. However, the high-performance isolation of CTCs remains significant challenges including achieving the sensitivity and specificity necessary due to their extreme rarity and severe biofouling in blood, such as billions of background cells and various proteins. With the advancement of CTCs detection technologies in recent years, the highly efficient and highly specific detection platforms for CTCs have gradually been developed, resulting in improving CTC capture efficiency, purity and sensitivity. In this review, we systematically describe the current strategies with surface modifications by utilizing the antifouling property of polymer, peptide, protein and cell membrane for high-performance enrichment of CTCs. To wrap up, we discuss the substantial challenges facing by current technologies and the potential directions for future research and development.

Laser-scribing graphene-based electrochemical biosensing devices for simultaneous detection of multiple cancer biomarkers.

In this study, a graphene electrochemical sensor based on laser graphene polymer material was proposed to induce graphene formation on polyimide substrates via fiber laser. The laser produces stable power and results to achieve the benefits of consistency, conductivity, and flexibility. The electrochemical three-electrodes were manufactured on polyimide to replace the traditional three-electrodes by achieving small size and portability. An electrode activation is the modification of laser-scribed graphene electrodes (LSG) to facilitate the binding of liver cancer sites. The evaluation is performed by differential pulse Voltammetry (DPV) to detect cancer proteins in the phosphate buffer saline (PBS) buffer and serum. In a serum environment, the concentrations of alpha-fetoprotein (AFP) and Carcinoembryonic antigen (CEA) were detected from 0.75 ng ml-1 to 100 ng ml-1, AFP and CEA electrodes have a good linear range (R2 = 0.96 and R2 = 0.98), indicating the sensor's sensitivity and specificity for cancer detection. In addition, two types of carcinogenic proteins were monitored in the PBS and successfully detected in this experiment. Based on the results, the appropriate LSG sensor may be used for monitoring with limited resources. Electrode manufacturing is simple, fast, low-cost, small in size, convenient to carry, stable, instant detection, and flexible.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer

The mechanism of deleted in lymphocytic leukemia 2 (DLEU2)-long non-coding RNA in tumors has become a major point of interest in recent research related to the occurrence and development of a variety of tumors. Recent studies have shown that the long non-coding RNA DLEU2 (lncRNA-DLEU2) can cause abnormal gene or protein expression by acting on downstream targets in cancers. At present, most lncRNA-DLEU2 play the role of oncogenes in different tumors, which are mostly associated with tumor characteristics, such as proliferation, migration, invasion, and apoptosis. The data thus far show that because lncRNA-DLEU2 plays an important role in most tumors, targeting abnormal lncRNA-DLEU2 may be an effective treatment strategy for early diagnosis and improving the prognosis of patients. In this review, we integrated lncRNA-DLEU2 expression in tumors, its biological functions, molecular mechanisms, and the utility of DLEU2 as an effective diagnostic and prognostic marker of tumors. This study aimed to provide a potential direction for the diagnosis, prognosis, and treatment of tumors using lncRNA-DLEU2 as a biomarker and therapeutic target (AU)

LncRNA CASC19: a novel oncogene involved in human cancer

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial–mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers (AU)

The development of radioresistant oral squamous carcinoma cell lines and identification of radiotherapy-related biomarkers

Background In the treatment of oral squamous cell carcinoma (OSCC), radiation resistance remains an important obstacle to patient outcomes. Progress in understanding the molecular mechanisms of radioresistance has been limited by research models that do not fully recapitulate the biological features of solid tumors. In this study, we aimed to develop novel in vitro models to investigate the underlying basis of radioresistance in OSCC and to identify novel biomarkers. Methods Parental OSCC cells (SCC9 and CAL27) were repeatedly exposed to ionizing radiation to develop isogenic radioresistant cell lines. We characterized the phenotypic differences between the parental and radioresistant cell lines. RNA sequencing was used to identify differentially expressed genes (DEGs), and bioinformatics analysis identified candidate molecules that may be related to OSCC radiotherapy. Results Two isogenic radioresistant cell lines for OSCC were successfully established. The radioresistant cells displayed a radioresistant phenotype when compared to the parental cells. Two hundred and sixty DEGs were co-expressed in SCC9-RR and CAL27-RR, and thirty-eight DEGs were upregulated or downregulated in both cell lines. The associations between the overall survival (OS) of OSCC patients and the identified genes were analyzed using data from the Cancer Genome Atlas (TCGA) database. A total of six candidate genes (KCNJ2, CLEC18C, P3H3, PIK3R3, SERPINE1, and TMC8) were closely associated with prognosis. Conclusion This study demonstrated the utility of constructing isogenic cell models to investigate the molecular changes associated with radioresistance. Six genes were identified based on the data from the radioresistant cells that may be potential targets in the treatment of OSCC (AU)

Oncogenic roles of GPR176 in breast cancer: a potential marker of aggressiveness and a potential target of gene therapy

Background Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. Methods GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. Results Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breast cancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. Conclusion These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy (AU)

Biomarcadores pronósticos en el uso del radio-223 en pacientes con cáncer de próstata metastásico resistente a la castración / Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistant prostate cancer

Objetivos Establecer biomarcadores basales en pacientes con cáncer de próstata metastásico resistente a la castración (CPMRC) tratados con Ra-223 que predigan una mejor supervivencia global (SG), así como valorar la toxicidad hematológica y la respuesta. Materiales y métodos Estudio retrospectivo multicéntrico en 151 pacientes con CPMRC tratados con Ra-223 entre 2013 y 2020. Se valoró la SG de acuerdo a: los niveles basales de hemoglobina (Hb), el antígeno prostático específico (PSA), la fosfatasa alcalina (FA), la escala de dolor de la OMS, el Eastern Cooperative Oncology Group (ECOG), el número de lesiones en gammagrafía ósea (GO), el uso de agentes de protección ósea y las dosis recibidas. Se determinó el grado de toxicidad hematológica y la respuesta basada en los cambios de la FA y el dolor pre y postratamiento. Resultados Mediana de SG de 24meses (IC95%: 16,5-31). En el 70% que recibieron tratamiento completo (5-6dosis) la mediana de SG fue de 34,9meses, versus 5,8 en el tratamiento incompleto (1-4dosis). La SG fue mayor en los pacientes con menor PSA, FA, Hb>13g/dl, menor número de metástasis óseas y ECOG 0-1. 52/151pacientes (34%) fallecieron durante el seguimiento. Cerca del 70% de los pacientes presentaron disminución del dolor, y el 66%, reducción de la FA. La mitad de los pacientes presentaron eventos adversos hematológicos leves, y solo el 5%, severos. Conclusiones Los pacientes con CPMRC tratados con Ra-223 que presentan biomarcadores basales como Hb>13g/ml, ECOG 0-1, PSA<20ng/ml y menor número de lesiones en GO muestran mejor SG, con un adecuado perfil de seguridad (AU)

Objectives Establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with Ra-223 that predicted a better overall survival (OS), assess hematology toxicity and treatment response. Materials and methods Retrospective multicenter study in 151 patients with mCRPC between 2013 and 2020. OS was assessed according to basal hemoglobin (Hb), PSA, alkaline phosphatase (AP), WHO pain scale, Eastern Cooperative Oncology Group (ECOG), number of metastatic lesions on bone scan (BS), use of protective bone agents and received. Hematological toxicities were evaluated. Treatment response was based on changes in FA and pain. Results Median OS was 24months (95%CI: 16.5-31). OS in 70% of patients who received complete Ra-223 treatment (5-6 doses) was 34.9m vs. 5.8m in patients with incomplete treatment (1-4 doses). OS was longer in patients with lower PSA and AP, Hb>13g/dL, lesser bone metastasis on GO and ECOG 0-1. 52/151 patients (34%) died during follow-up. Nearly 70% of patients experienced decrease in pain and 66% reduction on AP. Half of patients had mild hematological adverse effects and only 5% had severe. Conclusions mCRPC patients treated with Ra-223 who had Hb>13g/mL, ECOG 0-1, low AP, PSA<20ng/ml and lesser bone metastasis on BS shown a better OS with adequate safety profile (AU)

A contrast set mining based approach for cancer subtype analysis.

The task of detecting common and unique characteristics among different cancer subtypes is an important focus of research that aims to improve personalized therapies. Unlike current approaches mainly based on predictive techniques, our study aims to improve the knowledge about the molecular mechanisms that descriptively led to cancer, thus not requiring previous knowledge to be validated. Here, we propose an approach based on contrast set mining to capture high-order relationships in cancer transcriptomic data. In this way, we were able to extract valuable insights from several cancer subtypes in the form of highly specific genetic relationships related to functional pathways affected by the disease. To this end, we have divided several cancer gene expression databases by the subtype associated with each sample to detect which gene groups are related to each cancer subtype. To demonstrate the potential and usefulness of the proposed approach we have extensively analysed RNA-Seq gene expression data from breast, kidney, and colon cancer subtypes. The possible role of the obtained genetic relationships was further evaluated through extensive literature research, while its prognosis was assessed via survival analysis, finding gene expression patterns related to survival in various cancer subtypes. Some gene associations were described in the literature as potential cancer biomarkers while other results have been not described yet and could be a starting point for future research.

Familiarity and Perceptions of Ovarian Cancer Biomarker Testing and Targeted Therapy: A Survey of Oncology Nurses in the United States.

OBJECTIVES: To assess oncology nurses' awareness of biomarker testing and targeted therapy for ovarian cancer. SAMPLE & SETTING: 100 oncology nurses completed an online survey in June 2022. METHODS & VARIABLES: A cross-sectional survey was used to examine nurses' understanding of ovarian cancer testing and treatments, assess barriers, and identify opportunities for further education. RESULTS: Almost all respondents believed biomarker testing and targeted therapy were very/extremely important in diagnosing and supporting treatment of patients with ovarian cancer. Nurses were very/extremely familiar with cancer antigen 125 and germline testing, but fewer reported the same familiarity with somatic testing. Most nurses were familiar with targeted therapy for ovarian cancer, but only about half were very/extremely familiar with poly(ADP-ribose) polymerase (PARP) inhibitors. Less than half felt highly knowledgeable about PARP inhibitors. IMPLICATIONS FOR NURSING: It is important that oncology nurses understand biomarker testing and targeted therapy. There is an opportunity to provide resources to nurses to help them become more comfortable with PARP inhibitors in particular.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM).

Objective.The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented.Approach.The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring theγ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery.Main results.Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure theγ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate theγ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm.Significance.Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Proteome-wide mendelian randomization study implicates therapeutic targets in common cancers.

BACKGROUND: The interest in targeted cancer therapies has been growing rapidly. While numerous cancer biomarkers and targeted treatment strategies have been developed and employed, there are still significant limitations and challenges in the early diagnosis and targeted treatment of cancers. Accordingly, there is an urgent need to identify novel targets and develop new targeted drugs. METHODS: The study was conducted using combined cis-Mendelian randomization (cis-MR) and colocalization analysis. We analyzed data from 732 plasma proteins to identify potential drug targets associated with eight site-specific cancers. These findings were further validated using the UK Biobank dataset. Then, a protein-protein interaction network was also constructed to examine the interplay between the identified proteins and the targets of existing cancer medications. RESULTS: This MR analysis revealed associations between five plasma proteins and prostate cancer, five with breast cancer, and three with lung cancer. Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. Our study indicatied that genetically predicted KDELC2 (OR: 0.89, 95% CI 0.86-0.93) and TNFRSF10B (OR: 0.74, 95% CI 0.65-0.83) are inversely associated with prostate cancer. Furthermore, we observed an inverse association between CPNE1 (OR: 0.96, 95% CI 0.94-0.98) and breast cancer, while PDIA3 (OR: 1.19, 95% CI 1.10-1.30) were found to be associated with the risk of breast cancer. In addition, we also propose that SPINT2 (OR: 1.05, 95% CI 1.03-1.06), GSTP1 (OR: 0.82, 95% CI 0.74-0.90), and CTSS (OR: 0.91, 95% CI 0.88-0.95) may serve as potential therapeutic targets in prostate cancer. Similarly, GDI2 (OR: 0.85, 95% CI 0.80-0.91), ISLR2 (OR: 0.87, 95% CI 0.82-0.93), and CTSF (OR: 1.14, 95% CI 1.08-1.21) could potentially be targets for breast cancer. Additionally, we identified SFTPB (OR: 0.93, 95% CI 0.91-0.95), ICAM5 (OR: 0.95, 95% CI 0.93-0.97), and FLRT3 (OR: 1.10, 95% CI 1.05-1.15) as potential targets for lung cancer. Notably, TNFRSF10B, GSTP1, and PDIA3 were found to interact with the target proteins of current medications used in prostate or breast cancer treatment. CONCLUSIONS: This comprehensive analysis has highlighted thirteen plasma proteins with potential roles in three site-specific cancers. Continued research in this area may reveal their therapeutic potential, particularly KDELC2, TNFRSF10B, CPNE1, and PDIA3, paving the way for more effective cancer treatments.

CYFIP2 serves as a prognostic biomarker and correlates with tumor immune microenvironment in human cancers.

BACKGROUND: The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. METHODS: In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. RESULTS: We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. CONCLUSION: Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.

Bulk RNA-seq and scRNA-seq reveal SLC7A11, a key regulatory molecule of ferroptosis, is a prognostic-related biomarker and highly related to the immune system in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Ferroptosis is an iron-dependent, non-apoptotic cell death mode, highly correlated with the tumorigenesis and progression of multiple cancers. Solute carrier family 7 member 11 (SLC7A11) maintains the anti-porter activity of cysteine and glutamate to regulate ferroptosis. We collected bulk RNA-seq and scRNA-seq from The Cancer Genome Altas and Gene Expression Omnibus databases. Then, we extracted the expression level of SLC7A11 to perform the differential expression analysis between normal tissues and LUAD tissues. Then, we applied survival, univariate, and multivariate Cox regression analyses to investigate the predictive value of SLC7A11 in LUAD. Gene set enrichment analysis was used to explore the underlying molecular mechanisms of SLC7A11 in LUAD. Finally, we analyzed the relationship of SLC7A11 to the immune status and the curative effect of immunotherapy. The expression level of SLC7A11 in LUAD tissues was markedly increased. The survival analysis, univariate and multivariate Cox regression analysis showed that SLC7A11 was a negative factor for the prognosis of LUAD patients. Gene set enrichment analysis revealed that several immune-related pathways were enriched in the low-level group. The lower SLC7A11 level has a better therapeutic effect of immunotherapy and less probability of immune escape and dysfunction. SLC7A11 was a prognostic-related biomarker and closely correlated with the immune status and therapeutic effect of immunotherapy in LUAD, which could be an effective biomarker for evaluating the prognosis and the therapeutic efficacy of immunotherapy.

The role of TNF-α and NFkß in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine.

PURPOSE: To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH). METHODS: Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis' test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney's test was used. P < 0.05 was considered significant. RESULTS: The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group. CONCLUSIONS: Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

Revisiting ab initio carcinoembryonic antigen and CA19-9 tumor markers in colorectal carcinoma in association with anatomotopographic location and staging of disease.

OBJECTIVE: This study purposed to evaluate preoperative two tumor markers, namely, carcinoembryonic antigen and carbohydrate antigen (CA)19-9, in colorectal cancer for anatomotopographic location with disease stage and to assess their utility for diagnostic staging purposes. METHODS: The study retrospectively incorporated patients who had undergone surgery for colorectal cancer at our department in 2015-2018 and in whom carcinoembryonic antigen and CA19-9 tumor markers had been preoperatively analyzed. The obtained data were then statistically processed using R-project. RESULTS: A total of 155 patients had been incorporated, of whom 96 (62%) were men and 59 (38%) were women. Rectum was the most common location (74 patients, 48%), and the least represented stage was IV (18, 12%). The marker carcinoembryonic antigen was obtained in all 155 cases, while CA19-9 was in 105. The median carcinoembryonic antigen was 3 (0.34-1104.25), and the median CA19-9 was 12 (0.18-840.00). A significance was recognized between median carcinoembryonic antigen and disease stage (p-value=0.016), with stages I, II, and III (medians 2, 3, and 2) different from stage IV (median 13), while no significance for CA19-9 was recognized (p-value=0.343). No significance between either marker and location (carcinoembryonic antigen: p=0.276; CA19-9: p=0.505) was detected. The testing was performed at a significance level of alpha=0.05. CONCLUSION: This study revealed a significance between the marker carcinoembryonic antigen, but not CA19-9, and the disease stage, while no relationship of either of these markers with tumor location was found. Herewith, the study confirmed that higher carcinoembryonic antigen values may suggest the finding of more advanced forms of colorectal cancer and thus a worse prognosis of this malignant phenomenon.

Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers.

Introduction: PI3K/AKT signaling pathway is upregulated in a broad spectrum of cancers. Among the class I PI3Ks (PI3Kδ/ß/δ isoforms), PI3Kδ has been implicated in hematologic cancers and solid tumors. Alternative splicing is a post-transcriptional process for acquiring proteomic diversity in eukaryotic cells. Emerging evidence has highlighted the involvement of aberrant mRNA splicing in cancer development/progression. Methods: Our previous studies revealed that PIK3CD-S is an oncogenic splice variant that promotes tumor aggressiveness and drug resistance in prostate cancer (PCa). To further evaluate the potential of utilizing PI3Kδ-S (encoded from PIK3CD-S) as a cancer biomarker and/or drug target, comprehensive analyses were performed in a series of patient samples and cell lines derived from endocrine/solid tumors. Specifically, IHC, immunofluorescence, western blot and RT-PCR assay results have demonstrated that PI3Kδ isoforms were highly expressed in endocrine/solid tumor patient specimens and cell lines. Results: Differential PIK3CD-S/PIK3CD-L expression profiles were identified in a panel of endocrine/solid tumor cells. SiRNA knockdown of PIK3CD-L or PIK3CD-S differentially inhibits AKT/mTOR signaling in PCa, breast, colon and lung cancer cell lines. Moreover, siRNA knockdown of PTEN increased PI3Kδ levels and activated AKT/mTOR signaling, while overexpression of PTEN reduced PI3Kδ levels and inhibited AKT/mTOR signaling in cancer cells. Intriguingly, PI3Kδ-S levels remained unchanged upon either siRNA knockdown or overexpression of PTEN. Taken together, these results suggested that PTEN negatively regulates PI3Kδ-L and its downstream AKT/mTOR signaling, while PI3Kδ-S promotes AKT/mTOR signaling without regulation by PTEN. Lastly, PI3Kδ inhibitor Idelalisib and SRPK1/2 inhibitor SRPIN340 were employed to assess their efficacies on inhibiting the PI3Kδ-expressing endocrine/solid tumors. Our results have shown that Idelalisib effectively inhibited PI3Kδ-L (but not PI3Kδ-S) mediated AKT/mTOR signaling. In contrast, SRPIN340 reversed the aberrant mRNA splicing, thereby inhibiting AKT/mTOR signaling. In-vitro functional assays have further demonstrated that a combination of Idelalisib and SRPIN340 achieved a synergistic drug effect (with drastically reduced cell viabilities/growths of tumor spheroids) in inhibiting the advanced tumor cells. Conclusion: In summary, our study has suggested a promising potential of utilizing PI3Kδ-S (an oncogenic isoform conferring drug resistance and exempt from PTEN regulation) as a prognostic biomarker and drug target in advanced endocrine cancers.

Efficacy of cell-free DNA as a diagnostic biomarker in breast cancer patients.

Breast cancer is the most prevalent and leading cause of mortality worldwide among women. Cell-free DNA (cfDNA) analysis is an alternative quantitative approach to conventional methods for cancer diagnosis. The current research project aimed to determine the efficacy of cfDNA as a diagnostic biomarker in breast cancer patients in Pakistan. Eighty-four female breast cancer patients were selected as cases, and 152 healthy females as controls. Immunohistochemistry was performed to identify tumor biomarkers along with clinical profiling. cfDNA was extracted from serum using the phenol-chloroform method. The cfDNA level in the serum was estimated using Agarose Gel Electrophoresis and Nanodrop. SPPS version 25.0 was used to perform statistical analyses. The results showed that the cancer biomarkers were significantly associated with breast cancer. The changes in hematological parameters were insignificant, whereas the biochemical parameter variations between the cases and controls were statistically significant. A significant association of cfDNA level with breast cancer was observed. Further cfDNA levels and cancer biomarkers were not statistically significant. A significant correlation was observed between cfDNA and biochemical parameters, except for creatinine, whereas hematological parameters showed no significant correlation.ROC analysis declared cfDNA as an authentic diagnostic marker for breast cancer. It was concluded that the level of cfDNA is significantly increased in breast cancer patients and can be utilized as a diagnostic biomarker.

An all-in-one enzymatic DNA network based on catalytic hairpin assembly for label-free and highly sensitive detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), identified as a prospective cancer biomarker, plays a vital role in the occurrence and progression of cancer cell lines and impacts on genome stability. However, conventional approaches typically rely on the interactions between the antigen and antibody, limiting their utility for qualitative assessments of APE1 expression. Herein, an all-in-one enzymatic DNA network (EDN) assay with catalytic hairpin assembly for label-free and ultrasensitive detection of APE1 has been developed. In this work, the blocking strand can inhibit the initiator by obstructing the complementary region, preventing the hairpin from hybridizing in the absence of APE1 targets. While the presence of targets can activate the unlocking of the initiator, which can trigger the catalytic hairpin reaction, and increase the fluorescent signal. Under optimal conditions, the developed sensing method can detect the target APE1 down to 4.78 × 10-6 U mL-1 with a wide linear range from 5 × 10-6 U mL-1 to 30 U mL-1. This strategy has also been successfully applied to the analysis of complicated biological samples compared to ELISA, demonstrating its potential applications in biochemical and molecular biology research as well as clinical diagnostics. Overall, benefiting from the high amplification efficiency, this strategy has successfully and simply detected low-abundance APE1 without additional enzyme isolation steps, presenting great potential for clinical detection applications.