Cancer Samples Research Articles

EP.04C.09 Liquid Biopsy Assay to Detect Low Levels of ctDNA in Early-Stage Lung Cancer Samples

EP.04C.09 Liquid Biopsy Assay to Detect Low Levels of ctDNA in Early-Stage Lung Cancer Samples

The mechanism of L1 cell adhesion molecule interacting with protein tyrosine kinase 2 to regulate the focal adhesion kinase–growth factor receptor-bound protein 2–son of sevenless–rat sarcoma pathway in the identification and treatment of type I high-risk endometrial cancer

Objective: The objective of this study was to investigate how L1 cell adhesion molecule (L1CAM) interacting with protein tyrosine kinase 2 (PTK2) affects endometrial cancer (EC) progression and determine its association with the focal adhesion kinase (FAK)–growth factor receptor-bound protein 2 (GRB2)–son of sevenless (SOS)–rat sarcoma (RAS) pathway. EC is a female cancer of major concern in the world, and its incidence has increased rapidly in recent years. L1CAM is considered a reliable marker of poor prognosis in patients with EC. Material and Methods: A single-center and prospective study was conducted using data from the Cancer Genome Atlas and samples from normal and EC tissues to explore the differential expression of L1CAM. Additional experimental models included human immortalized endometrial epithelium cells (hEECs) and EC cell lines such as KLE, RL95-2, and Ishikawa. L1CAM expression was regulated using lentiviruses designed for either overexpression or interference, and PTK2/focal adhesion kinase (FAK) signaling was inhibited with PF431396. Transfected KLE cells were injected into mice, and tumor growth was monitored over 14 days. Cellular proliferation and survival were assessed using cell counting kit, colony formation, and terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate (dUTP) nick-end labeling assays. Metastatic behavior was evaluated through Transwell assays for cell migration and invasion. The expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were determined by Western blot. In addition, the activation of the FAK–GRB2–SOS–RAS pathway was examined by assessing the protein levels of FAK, GRB2, SOS, and RAS. Results: There was a significant difference in L1CAM expression between EC tumor tissues and normal tissues, and L1CAM messenger RNA (1.85-fold) and L1CAM protein (2.59-fold) were significantly more expressed in EC tissues (P < 0.01) than in normal tissues. The tumor growth of L1CAM overexpressing EC cells was faster than that of negative control EC cells (6.43 fold; P < 0.001). L1CAM promoted the expression of FAK (1.43-2.72-fold; P < 0.001); enhanced EC cell proliferation (P < 0.01), survival and motility (P < 0.001), migration (P < 0.001), and invasion (P < 0.001); and activated the FAK–GRB2–SOS–RAS pathway, all of which were reversed when FAK expression was not upregulated (P < 0.001). Conclusion: By upregulating PTK2 and its encoded protein FAK, L1CAM was found to promote tumor progression and increase the activation of the FAK–GRB2–SOS–RAS pathway. These findings establish L1CAM and PTK2 as reference genes for poor prognostic prediction in EC and as targets for EC therapy, providing a valuable basis for distinguishing between benign and malignant endometrial conditions and justifying the necessity of targeted therapeutic approaches.

Screening of Key Transcripts from Expression Data Using Applied Artificial Intelligence for Cancer Prediction

Research on the effects of artificial intelligence (AI)-driven solutions in the field of oncology is still being conducted all around the world. Applications of AI to identify the transcripts that cause cancer are being investigated, particularly when employing ensemble learning techniques. Ensemble feature fusion is the process of distributing the feature selection process and combining the local features that were chosen to create a smaller global feature set. This article addresses the use of ensemble feature fusion in the field of differential transcript expression analysis to screen for important transcripts linked to a disease. Owing to the necessity and significance of research in cancer diagnosis, an ensemble feature fusion approach experimental case study has been carried out using 109 liver cancer samples obtained from Mitranscriptome dataset. It was found that the expression data were used to filter the most pertinent transcripts, which allowed for the best possible differentiation between sample type. Accordingly, a set of 26 significant liver cancer causing transcripts has been screened using unanimous voting-scheme, giving an accuracy of percentage of 96. During generalization testing, cancer prediction classifiers constructed with this essential transcript collection shown excellent discriminating power and performed well in differentiating between normal and malignant cells. By resolving the “high dimension-low sample (High p Low n)” issue that is typically present in the expression data, this improves the predicting ability of cancer diagnostic systems. In the field of oncology, artificial intelligence-powered solutions will facilitate the development of applications that prioritize Sustainable Development Goal 3: Good Health and Well-Being.

Expression of claudin 18.2 in poorly cohesive carcinoma and its association with clinicopathologic parameters in East Asian patients

BackgroundPoorly cohesive carcinoma (PCC) is a distinct subtype of gastric cancer with limited therapeutic options. This study investigated claudin (CLDN) 18.2 expression status in PCCs using a 43–13 A clone. MethodsWe retrospectively collected 178 consecutive surgically resected stage Ⅱ–Ⅲ gastric cancer samples. Tissue microarray blocks were constructed for CLDN18.2 immunohistochemical staining. We studied CLDN18.2 expression and its association with clinicopathologic parameters. ResultsCLDN18.2 positivity (defined by ≥ 75 % of tumor cells showing moderate to strong membranous positivity) was found in 34.8 % of the PCC cases (62/178). Approximately half of the CLDN18.2 positive PCCs demonstrated heterogeneous expression (51.6 %, 32/62). CLDN18.2 positivity was not associated with any clinicopathologic parameters examined. However, CLDN18.2 positivity tended to be more frequent in E-cadherin-positive PCCs (no loss of expression) than in E-cadherin-negative PCCs (loss of expression) (50 % vs. 27.7 %). The CLDN18.2 expression level, represented by the H-score, gradually decreased as the paraffin block storage time increased (P = 0.046). Overall survival and disease-free survival analyses showed no significant difference between CLDN18.2-positive and negative PCCs. ConclusionsA significant portion of surgically resected PCC specimens showed CLDN18.2 positivity. Additionally, since the expression level of CLDN18.2 gradually decreases with increased paraffin block storage time, reflex testing can be considered at the time of the cancer diagnosis.

Identification of a PANoptosis-related prognostic model in triple-negative breast cancer, from risk assessment, immunotherapy, to personalized treatment

BackgroundTriple-negative breast cancer is a breast cancer subtype characterized by its challenging prognosis, and establishing prognostic models aids its clinical treatment. PANoptosis, a recently identified type of programmed cell death, influences tumor growth and patient outcomes. Nonetheless, the precise impact of PANoptosis-related genes on the prognosis of triple-negative breast cancer has yet to be determined. MethodsClinical information for the triple-negative breast cancer samples was collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases, while 19 PANoptosis-related genes were sourced from previous studies. We first categorized PANoptosis-related subtypes and determined the differentially expressed genes between them. Subsequently, we developed and validated a PANoptosis-associated predictive model using LASSO and Cox multivariate regression analyses. Statistical evaluations were conducted using R software, and the mRNA expression levels of the genes were quantified using real-time PCR. ResultsUsing consensus clustering analysis, we divided triple-negative breast cancer patients into two clusters based on PANoptosis-related genes and identified 1054 differentially expressed genes between these clusters. Prognostic-related genes were subsequently selected to re-cluster patients, validating their predictive ability. A prognostic model was then constructed based on four genes: BTN2A2, CACNA1H, PIGR, and S100B. The expression and enriched cell types of these genes were examined and the expression levels were validated in vitro. Furthermore, the model was validated, and a nomogram was created to enhance personalized risk assessment. The risk score, proven to be an independent prognostic indicator for triple-negative breast cancer, showed a positive correlation with both age and disease stage. Immune infiltration and drug sensitivity analyses suggested appropriate therapies for different risk groups. Mutation profiles and pathway enrichment were analyzed, providing insights into potential therapeutic targets. ConclusionA PANoptosis-related prognostic model was successfully developed for triple-negative breast cancer, offering a novel approach for predicting patient prognosis and guiding treatment strategies.

Characterization of Molecular Subtypes of Rat Mammary Cancer and Their Association With Environmental Exposures.

Breast cancer is a heterogeneous disease with many subtypes, and the association between these subtypes and exposure to environmental factors such as radiation remains controversial. Although the rat is used widely for research into human breast cancer, the heterogeneity and subtype definitions are unclear. Here, we leveraged an archive of rat mammary cancer samples and gene expression microarray data to classify tumors and examine their association with exposures. Eighty-four mammary cancer and 12 normal mammary tissue samples were obtained from previous experiments in which rats were exposed to different types of radiation, chemical carcinogens, and diets. Tumors were then subjected to immunohistochemical (IHC) analysis of conventional biomarkers, as well as gene expression profiling; they were then classified by three approaches based on IHC results, the PAM50 classifier algorithm, and unsupervised clustering of gene expression profiles. IHC identified four subtypes (luminal A-like, luminal B-like 1, luminal B-like 2, and triple-negative), while PAM50 identified six (luminal A, luminal B, basal-like, HER2-enriched, normal-like, and claudin-low). Unsupervised clustering divided the tumors into three large, statistically significant, groups (named "luminal A", "luminal B", and "non-luminal" clusters). The results of the three approaches were significantly associated with each other. Exposure to radiation and chemical carcinogens during post-pubertal development was significantly associated with an increased risk of developing luminal A tumors, whereas exposure to a high corn-oil diet was associated with a higher likelihood of luminal B tumors. Rat mammary cancer subtypes resemble those in humans and are related to environmental factors.

Long non-coding RNA FAM87A is associated with overall survival and promotes cell migration and invasion in gastric cancer.

The role of long non-coding RNAs (lncRNAs) in the invasion and metastasis of gastric cancer remains largely unclear. Integrating transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes were identified in gastric cancer. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) database-curated gene set, lncRNAs associated with invasion and metastasis were identified. The Cox analyses were performed to identify prognostic lncRNAs. The competing endogenous RNA (ceRNA) regulation network was constructed to identify hub lncRNAs in gastric cancer. Functional and pathway analyses were used to investigate the function of identified lncRNAs. RT-qPCR and Transwell assays were used to investigate the expression in gastric cancer tissues and functions in gastric cancer cell lines. Based on GEO and TCGA databases, 111 differentially expressed lncRNAs were identified between gastric cancer and normal samples. A total of 43 lncRNAs were significantly correlated with hallmark genes of cancer invasion and metastasis. Among them, as a hub lncRNA in the invasion-related ceRNA regulation network, FAM87A showed potential regulation on MAPK signaling and transforming growth factor (TGF) signaling cascade, such as TGFB2, TGFBR1, and TGFBR2. Furthermore, FAM87A also showed a significant correlation with cell adhesion molecules, such as Integrin alpha 6 (ITGA6) and Contactin-1 (CNTN1). RT-qPCR experiments showed that FAM87A expression was upregulated in gastric cancer tissues compared to normal samples (n = 30). Transwell assays showed that FAM87A knockdown inhibited the migration and invasion abilities of gastric cancer cells in vitro. Notably, clinical data analysis showed that lncRNA FAM87A could be an independent factor for the overall survival of patients with gastric cancer. LncRNA FAM87A may play a pivotal role in regulating migration and invasion of gastric cancer cells. FAM87A could be a potential biomarker for the overall survival of patients with gastric cancer.

A Machine Learning-Based Investigation of Integrin Expression Patterns in Cancer and Metastasis.

Integrins, a family of transmembrane receptor proteins, play complex roles in cancer development and metastasis. These roles could be better delineated through machine learning of transcriptomic data to reveal relationships between integrin expression patterns and cancer. We collected publicly available RNA-Seq integrin expression from 8 healthy tissues and their corresponding tumors, along with data from metastatic breast cancer. We then used machine learning methods, including t-SNE visualization and Random Forest classification, to investigate changes in integrin expression patterns. Integrin expression varied across tissues and cancers, and between healthy and cancer samples from the same tissue, enabling the creation of models that classify samples by tissue or disease status. The integrins whose expression was important to these classifiers were identified. For example, ITGA7 was key to classification of breast samples by disease status. Analysis in breast tissue revealed that cancer rewires co-expression for most integrins, but the co-expression relationships of some integrins remain unchanged in healthy and cancer samples. Integrin expression in primary breast tumors differed from their metastases, with liver metastasis notably having reduced expression. Integrin expression patterns vary widely across tissues and are greatly impacted by cancer. Machine learning of these patterns can effectively distinguish samples by tissue or disease status.

The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a key component of the exon junction complex (EJC) and is extensively involved in RNA splicing, inducing mRNA decay, and regulating the cell cycle and apoptosis. However, the potential role of EIF4A3 in EC has not been comprehensively investigated and remains unknown. Here, we report that the expression level of EIF4A3 is dramatically elevated in endometrial cancer (EC) samples compared with normal EC samples via bioinformatics analysis and immunohistochemistry analysis, and that high expression of EIF4A3 promotes the proliferation, migration, and invasion of EC cells. Mechanistically, we found that high EIF4A3 expression stabilized cell division cyclin 20 (CDC20) mRNA, and high EIF4A3 expression induced pro-carcinogenic effects in EC cells that were efficiently antagonized upon knockdown of CDC20, as well as Apcin, an inhibitor of CDC20. These findings reveal a novel mechanism by which high expression of EIF4A3 induces CDC20 upregulation, thus leading to EC tumorigenesis and metastasis, indicating a potential treatment strategy for EC patients with high EIF4A3 expression using Apcin. KEY MESSAGES: The expression level of EIF4A3 was dramatically elevated in endometrial cancer (EC) samples compared with normal endometrial cancer samples. High EIF4A3 expression stabilized CDC20 mRNA, and high EIF4A3 expression induced pro-carcinogenic effect in EC cells which was efficiently antagonized upon knockdown of CDC20. Apcin, an inhibitor of CDC20, could effectively counteract high expression of EIF4A3 inducing EC tumourigenesis and metastasis, indicating the potential treatment strategy for EC patients with EIF4A3 high expression by using Apcin.

Exploring the Role of Escherichia coli K-12 in Reducing MIR17HG Expression as a Poor Prognostic Biomarker in Colorectal Cancer

Background: Long noncoding RNAs (lncRNAs) play significant roles in various cellular processes, and alterations in their expression levels can contribute to the pathogenesis of colorectal cancer (CRC). Objectives: This study aims to identify lncRNAs highly associated with poor prognosis in CRC and determine those that exhibit significant expression changes under the influence of Escherichia coli K-12. Methods: Potentially susceptible lncRNAs to expression modulation in the presence of E. coli K-12 were identified by analyzing GSE50040 datasets. Data from the cancer genome Atlas (TCGA) were utilized to assess E. coli K-12-affected lncRNAs with the most significant impact on CRC pathogenesis. The association between the candidate lncRNA and patient prognosis was investigated using clinical data. The co-expression network was employed to identify pathways related to the identified lncRNA via the MsigDB database. To validate the in silico findings, CRC and adjacent normal samples were examined using the RT-qPCR method. Results: Cox regression analysis demonstrated that MIR17HG is a strong biomarker associated with poor prognosis in CRC patients. Increased expression of MIR17HG in cancer samples was correlated with key pathways involving cell proliferation, anti-apoptosis, and metastasis. RT-qPCR results showed that the expression level of MIR17HG in CRC samples was significantly higher than in normal samples. Further analysis revealed that MIR17HG expression is susceptible to suppression by E. coli K-12. Conclusions: High expression of MIR17HG in cancer samples is associated with an increased probability of mortality in CRC patients. Our study highlights the potential of E. coli K-12 to reduce CRC malignancy by downregulating MIR17HG expression.

Targeting CD47 and Angiogenesis Demonstrates Effective Anti-Tumor Effect in Bladder Cancer.

Background: Although immunotherapy has shown potential in cancer treatment, current immunotherapeutics for bladder cancer are limited by a low response rate. Therefore, it is necessary to investigate other suitable immunotherapeutic targets and strategies for bladder cancer. Methods: To evaluate whether CD47 could be a suitable target for bladder cancer immunotherapy, CD47 protein expression levels in 116 bladder cancer tissue samples were assessed by IHC staining. In vitro anti-tumor effect of blocking CD47 was examined by phagocytosis assays. In vivo anti-tumor effects of targeting CD47 and angiogenesis were experimented in the HSPCs-CDX model. Results: We find that CD47 is highly expressed in bladder cancer samples and is associated with poor prognosis. Blocking CD47 could enhance the human PBMC-derived macrophages' phagocytosis of T24 (from 10.40% to 29.70%) and 5637 (from 5.31% to 33.52%) human bladder cancer cells, as well as demonstrate anti-tumor effects in the HSPCs-CDX model (tumor growth inhibition rate, TGI: 33.05%). During CD47 treatment, we observed that the level of angiogenesis increased after CD47 blockade, and it might undermine the effect of CD47 immunotherapy. We then combined CD47 blockade with anti-angiogenic drugs to treat bladder cancer and discovered that inhibiting angiogenesis could further improve the anti-tumor effect of CD47 blockade (TGI: 76.39%). Finally, we tested the anti-tumor effect of co-targeting CD47 and angiogenesis using a bispecific fusion protein, SIRPα-VEGFR1, which successfully inhibited tumor growth to a similar extent as a combination therapy. Conclusions: Our study suggests that targeting CD47 could inhibit the growth of bladder cancer by promoting macrophage-mediated anti-tumor immunity. Moreover, blocking CD47 and angiogenesis could achieve a potent anti-tumor effect and could be an effective immunotherapy strategy for bladder cancer.

Dysbiosis in Human Urinary Microbiota May Differentiate Patients with a Bladder Cancer.

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter, Cutibacterium, Alloscardovia, Moryella, and Anaeroglobus, that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium, and Bifidobacterium, exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

High expression of PAX8-AS1 correlates with poor prognosis and response to fluorouracil-based chemotherapy in stage II colon cancer

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Gut mucosa alterations after kidney transplantation: a cross sectional study.

Kidney transplant recipients (KTRs) rely on immunosuppressants like mycophenolate to prevent organ rejection. However, mycophenolate often causes intestinal symptoms and inflammation in various organs, including the skin and the colon. While KTRs have an increased risk for skin cancer, the risk of colorectal cancer is not increased. Elucidating the histological alterations in the colon of KTRs and comparing these changes with known skin alterations would help understand how immunosuppressants influence cancer development and progression. Whole slide images from gut biopsies (Non-transplanted subjects n = 35, KTRs n = 49) were analyzed using the ImageJ and R programming environment. A total of 22,035 epithelial cells, 38,870 interstitial cells, 3465 epithelial cell mitoses, and 7477 endothelial cells, each characterized by multiple microscopy parameters, from a total of 1788 glands were analyzed. The large database was subsequently analyzed to verify the changes of inflammatory milieu in KTRs and in cancer. KTRs without colon-cancer showed a significantly higher density of interstitial cells in the colon compared to non-transplanted patients. Moreover, the increase in interstitial cell number was accompanied by subtle modifications in the architecture of the colon glands, without altering the epithelial cell density. We could not identify significant structural modifications in cancer samples between KTRs and non-transplanted patients. Our findings demonstrate an increased number of resident interstitial cells in the colon of KTRs, as in other patients treated with mycophenolate. These changes are associated with subtle alterations in the architecture of colon glands.

Zinc finger protein 263 promotes colorectal cancer cell progression by activating STAT3 and enhancing chemoradiotherapy resistance

Zinc finger protein 263 (ZNF263) is frequently upregulated in various tumor types; however, its function and regulatory mechanism in colorectal cancer (CRC) have not yet been elucidated. In this study, the expression of ZNF263 was systematically examined using data from The Cancer Genome Atlas database and samples from patients with CRC. The results indicated that high expression of ZNF263 in CRC tissues is significantly associated with tumor grade, lymph node metastasis and disant metastasis. Additionally, overexpression of ZNF263 significantly promoted the proliferation, invasion, migration, and epithelial-mesenchymal transition of CRC cells, while also increasing signal transducer and activator of transcription 3 (STAT3) expression and mRNA stability. Conversely, knockdown of ZNF263 inhibited the malignant behavior of CRC cells and decreased STAT3 expression and mRNA stability. Further mechanism studies using chromatin immunoprecipitation (CHIP) and luciferase assays verified that ZNF263 directly binds to the STAT3 promoter. Rescue experiments demonstrated that the knockdown or overexpression of STAT3 could significantly reverse the effects of ZNF263 on CRC cells. Additionally, our study found that overexpression of ZNF263 enhanced the resistance of CRC cells to the chemoradiotherapy. In summary, this study not only elucidated the significant role of ZNF263 in CRC but also proposed novel approaches and methodologies for the diagnosis and treatment of this malignancy.

Silencing EPHB2 diminished the malignant biological properties of esophagus cancer cells by blocking autophagy and Wnt/β-catenin pathway.

Eph receptor B2 (EPHB2) is overexpressed in some tumors and relevant to unfavorable outcomes of tumor patients. By searching Gene Expression Profiling Interactive Analysis and KM Plot websites, we discovered that EPHB2 was highly expressed in patients with esophageal cancer, leading to poor prognosis. However, the role and molecular mechanism of EPHB2 in esophagus cancer is unknown. Our study aims to unveil the underlying mechanism by which EPHB2 modulates the biological properties of esophagus cancer cells. After si-EPHB2 transfection, the malignant biological properties of esophagus cancer cells were determined by several biological experiments. IWP-4 was applied to block Wnt/β-catenin signaling pathway. The expressions of autophagy and Wnt/β-catenin signaling pathway relevant molecules were tested by western blot assay. An increased expression of EPHB2 was happened in esophagus cancer samples and loss of EPHB2 diminished esophagus cancer cells proliferation, migration, and invasion. Moreover, our data showed that depletion of EPHB2 blocked the autophagy and in-activated Wnt/β-catenin signaling pathway in esophagus cancer cells. While, IWP-4 treatment inhibited the autophagy and limited esophagus cancer cells proliferation, migration, and invasion. Moreover, EPHB2 knocked down strengthened the effect of IWP-4 treatment in regulating esophagus cancer cells proliferation, migration, and invasion. Finally, we illustrated that EPHB2 regulated the biological properties of esophagus cancer cells by modulating autophagy and Wnt/β-catenin signaling pathway. Our study illustrated that EPHB2 might be a worthwhile target considering for the treatment of esophagus cancer.

MiR-148 and miR-375 expression in oral squamous cell carcinoma patients with oral infection in comparison with OSCC patients without oral infection

Background: Oral squamous cell carcinoma is a multifactorial disease that is the sixth most common cancer worldwide. MicroRNAs have been confirmed to play a role in oral squamous cell carcinoma, acting as either oncogenes or tumor suppressor genes. This study examined the expression level and role of microR-148 and microR-375 in oral cancer. Methods: In this study, we used 30 cancer samples with infection and 30 cancer samples without infection. To analyze the expression of microRNA 375 and microRNA 148, we used real-time PCR. First, we extracted total RNA from the samples. Then, we generated cDNA from it. Finally, the obtained cDNA was used in the real-time PCR technique. Results: In cancer patients with oral infection, there was an increase in microRNA-148 expression and a decrease in microRNA-375 compared to cancer patients without oral infection. conclusion: The downregulation of microRNA-375 and upregulation of microRNA-148 can be utilized as diagnostic biomarkers and prognostic factors in oral cancer. Background: Oral squamous cell carcinoma is a multifactorial disease that is the sixth most common cancer worldwide. MicroRNAs have been confirmed to play a role in oral squamous cell carcinoma, acting as either oncogenes or tumor suppressor genes. This study examined the expression level and role of microR-148 and microR-375 in oral cancer. Methods: In this study, we used 30 cancer samples with infection and 30 cancer samples without infection. To analyze the expression of microRNA 375 and microRNA 148, we used real-time PCR. First, we extracted total RNA from the samples. Then, we generated cDNA from it. Finally, the obtained cDNA was used in the real-time PCR technique. Results: In cancer patients with oral infection, there was an increase in microRNA-148 expression and a decrease in microRNA-375 compared to cancer patients without oral infection. conclusion: The downregulation of microRNA-375 and upregulation of microRNA-148 can be utilized as diagnostic biomarkers and prognostic factors in oral cancer.

Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes

The immunophenoscore (IPS) is an important indicator for evaluating immunotherapy response. This work was designed to establish a prognostic model based on IPS-related genes in cervical cancer. Weighted correlation network analysis (WGCNA) was utilized to identify key modules related to IPS in cervical cancer data from The Cancer Genome Atlas (TCGA). The results show that the yellow module (158 genes) had a high correlation with both IPS_CTLA4_blocker and IPS_CTLA4_and PC1/PDL1/PDL2 blocker. Univariate cox regression analysis and LASSO regression analysis were performed based on 158 genes, and 9 characteristic genes were finally identified to construct the model. According to the differentially expressed genes, cervical cancer samples were divided into high-risk and low-risk groups and cluster 1.2.3. Higher risk scores associated with poorer prognosis. cluster2 and cluster3 were identified as cervical cancer subtypes with significant survival differences. cluster2 had higher immune cell infiltration levels and better prognosis, with greater sensitivity to Cyclopamine, Imatinib, MG-13, Paclitaxel, PHA-665752, Rapamycin, Sorafenib, Sunitinib, and VX-680. In contrast, cluster3 had higher TTN and PIK3CA mutations and greater sensitivity to AZ628, Dasatinib, Doxorubicin, HG-6-64-1, JQ12, Midostaurin, PF-562271, TAE684, and WH-4-023. In conclusion, we developed a feasible risk score model based on IPS-related genes for cervical cancer prognosis and identified potential drugs for different cervical cancer subtypes.

SNHG14 promotes triple-negative breast cancer cell proliferation, invasion, and chemoresistance by regulating the ERK/MAPK signaling pathway.

The functional role and molecular mechanisms of small-nucleolar RNA host gene 14 (SNHG14) in triple-negative breast cancer (TNBC) progression remain unclear. The expression levels of SNHG14 in breast cancer samples and cell lines were determined using real-time quantitative polymerase chain reaction. Cell proliferation, migration, and invasion abilities were detected using MTS and transwell assays. By RNA sequencing, differentially expressed genes were identified between the SNHG14 siRNA and the negative control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to predict the targets and pathways regulated by SNHG14. pRAF, pMEK, and pERK expression were measured by western blot. The xenograft model was constructed to access the biological function of SNHG14 in vivo. A minimal patient-derived xenograft model was established to evaluate the sensitivity to chemotherapy drugs. Our data indicated that SNHG14 expression was increased in TNBC tissues and cell lines. SNHG14 knockdown attenuated the proliferation, migration, and invasion abilities of TNBC cells both in vivo and in vitro. High SNHG14 expression was associated with lymph node metastasis and a high Ki67 index. The targets of SNHG14 were mainly enriched in the MAPK signaling pathway. pRAF, pMEK, and pERK expression were downregulated after being transfected with SNHG14 siRNA. Compared with the negative control group, the expression of CACNA1I, DUSP8, FGF17, FGFR4, FOS, PDGFRB, and DDIT3 was increased, and the expression of MKNK1 was decreased in the SNHG14 siRNA group. Minimal patient-derived xenograft model demonstrated that knockdown of SNHG14 enhanced the sensitivity to Docetaxel in vivo. Compared with the DMSO group, the proliferation of Docetaxel-resistant MDA-MB-231 cells was decreased in Dabrafenib, PD184352, and FR180204 treatment groups. SNHG14 knockdown inhibits TNBC progression by regulating the ERK/MAPK signaling pathway, which provides evidence for SNHG14 as a potential target for TNBC therapy.

Feasibility study of lncRNA DHRS4-AS1 sponge miR-222-3p in the diagnosis of thyroid cancer.

Thyroid cancer is a commonly occurring malignant tumour within the endocrine system, the incidence of which has been increasing steadily in our country. It has been the focus and direction of research in recent decades to continuously explore the diagnostic markers and molecular mechanisms of thyroid cancer and provide new possibilities for the healing of patients. In this study, lncRNA DHRS4-AS1 was identified as the research target, and the regulatory function of abnormal expression of DHRS4-AS1 on thyroid cancer was discussed. Thyroid cancer (116) and non-cancer normal (82) tissue samples were collected in this paper, and the expression of DHRS4-AS1 and miR-222-3p in tissues and cells were evaluated by RT-qPCR. CCK-8 and flow cytometry were used to detect cell survival status. The mechanism of DHRS4-AS1 sponge miR-222-3p was analysed by dual-luciferase reporter gene detection. In the present study, DHRS4-AS1 was down-regulated in both thyroid tissue and cell samples, while miR-222-3p expression was elevated. The ROC curve reflected the diagnostic value of DHRS4-AS1 in thyroid cancer [area under the curve (AUC) = 0.887, sensitivity = 76.7%, specificity = 95.1%]. DHRS4-AS1 regulates the development of thyroid cancer by targeting miR-222-3p. In addition, in vitro experiments demonstrated that overexpression of DHRS4-AS1 (pcDNA3.1-DHRS4-AS1) inhibited the proliferation of thyroid cancer cells and promoted cell apoptosis, while down-regulating the level of miR-222-3p. DHRS4-AS1 acts as a miR-222-3p sponge in thyroid cancer, and overexpression of DHRS4 AS1 down-regulates cell proliferation and promotes cell apoptosis. These findings demonstrate the potential of DHRS4-AS1 as a diagnostic factor for thyroid cancer.