Adjacent Tissues Research Articles

The Modified Caldwell-Luc Approach for Treating Odontogenic Maxillary Sinusitis Without Need for Functional Endoscopic Sinus Surgery: A Retrospective Study

BackgroundOdontogenic maxillary sinusitis is a common inflammatory condition resulting from the violation of the Schneiderian membrane by conditions arising from the dentoalveolar unit, which includes teeth, their supporting structures, and adjacent tissues. This study aims to evaluate a modified surgical approach for treating this condition. PurposeThe purpose of this study is to measure the frequency of re-treatment of maxillary sinusitis of odontogenic origin following treatment with a modified Caldwell-Luc approach, which involves accessing the maxillary sinus through the canine fossa without creating a counter-opening in the inferior nasal meatus. Study DesignThis retrospective cohort study included 82 cases (83 sinuses) with odontogenic sinusitis treated surgically with the modified Caldwell-Luc technique at the Department of Oral and Maxillofacial Surgery, Poriya Medical Center, between 2014 and 2021. Patients with non-odontogenic sinusitis were excluded. Predictor VariablesAnatomic findings defined as the presence or absence of ostiomeatal complex abnormalities and oroantral communication, as identified through clinical examination and CT imaging. Main Outcome VariablesThe need for retreatment, defined as the requirement for functional endoscopic sinus surgery (FESS) due to persistent signs and symptoms of maxillary sinusitis after the modified Caldwell-Luc procedure, including facial pain/pressure, nasal congestion, purulent nasal discharge, or radiographic evidence of persistent sinus opacification on CT scan, lasting more than 4 weeks despite appropriate medical management. CovariatesCovariates included demographic data (age, sex [male/female as identified at birth]), smoking status, etiologies of odontogenic sinusitis, and surgical conditions. AnalysesDescriptive statistics, Cox proportional hazards regression was used to compute hazard ratios. Kaplan-Meier survival analysis was performed to estimate the probability of remaining FESS-free over time. The level of statistical significance was set at p < 0.05. ResultsThe sample was composed of 82 patients (83 sinuses) with a mean age of 52.3 years (SD 13.5), and 47 (56.6%) were male. Dental implantation and sinus augmentation procedures were the most common etiologies of odontogenic sinusitis (50.6%). The median follow-up time was 6.03 months (IQR: 2.57 - 10.93 months). The incidence rate of FESS requirement was 2.64 per 100 person-months of follow-up. The FESS-free frequency was 89.2% (95% CI: 80.4% - 94.4%). The Kaplan-Meier analysis estimated the probability of remaining FESS-free at 12 months to be 89.1% (95% CI: 79.8% - 94.4%). Patients with OMC abnormalities had a hazard ratio of 2.25 (95% CI: 0.47-10.84, p = 0.31) for requiring FESS, while those with OAC had a hazard ratio of 1.85 (95% CI: 0.46-7.39, p = 0.38). Conclusions and RelevanceThe modified Caldwell-Luc procedure was effective in treating the majority of odontogenic sinusitis cases. FESS may be necessary in a small percentage of cases with persistent symptoms. Further research is needed to identify predictors for FESS requirement. Of note, we recommend that oral and maxillofacial surgery surgeons review sinusitis cases with a FESS surgeon before performing the modified Caldwell-Luc procedure creating the opportunity for simultaneous or closely timed procedures when necessary

Deubiquitinase OTUD7B Regulates Cell Proliferation in Breast Cancer

PurposeThe deubiquitylase OTUD7B plays a facilitates role in lung tumorigenesis through VEGF protein, but its role in breast cancer remains unclear. In the present study, we proposed to explore the role of deubiquitylase OTUD7B in breast cancer. MethodsThe expression of OTUD7B in breast cancer and adjacent tissues was detected. The role of OTUD7B in cell proliferation and invasion of breast cancer cell lines such as MCF-7 and MDA-MB-453 was explored. ResultsOTUD7B is highly expressed in human breast cancer tissues and its higher expression correlates with better survival of patients. Further mechanistic studies reveal that OTUD7B associates with RASGRF1 and PLCE1 to disrupt RAS signaling pathway. Knockdown of OTUD7B results in decreasing levels of RASGRF1 protein, suppression cell growth and invasion in breast cancer. Collectively, our results reveal a previously unappreciated anti-oncogentic role OTUD7B involved in RAS signaling pathway in breast cancer and indicate that deubiquitylases could induce tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent context.

Actin-related protein 2/3 complex subunit 1B promotes ovarian cancer progression by regulating the AKT/PI3K/mTOR signaling pathway.

Actin-related protein 2/3 complex subunit 1B (ARPC1B) is an essential subunit of the actin-related protein 2/3 (Arp2/3) complex. While there have been numerous research reports on Arp2/3 in relation to tumors, there needs to be more research on ARPC1B and its role in tumors, particularly at the pan-cancer level. Utilizing data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx) databases, we analyzed ARPC1B expression differences in normal, tumor, and adjacent tissues, investigating its correlation with prognosis and clinical stages in various cancers. We conducted gene enrichment analysis and explored ARPC1B's connection to the tumor immune microenvironment and its impact on anti-tumor drug resistance. In addition, in vivo and in vitro experiments have also been carried out to find the mechanism of ARPC1B on ovarian cancer (OV) proliferation and invasion. ARPC1B was highly expressed in 33 tumor types, suggesting its role as a tumor-promoting factor. Its expression correlated with poor prognosis and served as a clinical staging marker in over 10 tumor types. ARPC1B is implicated in various biological processes and signaling pathways, uniquely associated with tumor immunity, indicating immunosuppressive conditions in high-expression cases. High ARPC1B expression was linked to resistance to six anti-tumor drugs. Further experiments showed that ARPC1B can affect the proliferation, apoptosis, migration, and invasion of OV cells through the AKT/PI3K/mTOR pathway. ARPC1B is a biomarker for immune suppression, prognosis, clinical staging, and drug resistance, providing new insights for cancer therapeutics.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways “BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation” and “AMAN pathway”. In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Integrative transcriptome analysis identifies a crotonylation gene signature for predicting prognosis and drug sensitivity in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) stands as the most prevalent and treatment-resistant malignant tumour, characterized by a dismal prognosis. Croton acylation (CA) has recently gained attention as a critical factor in cancer pathogenesis. This study sought to rapidly identify prognostic features of HCC linked to CA. Differential analysis was conducted between tumour tissues and adjacent non-tumour tissues in the TCGA-LIHC and GSE76427 datasets to uncover differentially expressed genes (DEG1 and DEG2). The intersection of DEG1 and DEG2 highlighted DEGs with consistent expression patterns. Single-sample gene set enrichment analysis scores were calculated for 18 lysine crotonylation-related genes (LCRGs) identified in prior research, showing significant differences between tumour and normal groups. Subsequently, weighted gene co-expression network analysis was employed to identify key module genes correlated with the LCRG score. Candidate genes were identified by overlapping consistently expressed DEGs with key module genes. Prognostic features were identified, and risk scores were determined via regression analysis. Patients were categorized into risk groups based on the optimal cutoff value. Gene set enrichment analysis (GSEA) and immunoassays were also performed. The prognostic features were further validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 88 candidate genes were identified from 1179 consistently expressed DEGs and 4200 key module genes. Seven prognostic features were subsequently identified: TMCO3, RAP2A, ITGAV, ZFYVE26, CHST9, HMGN4, and KLHL21. GSEA revealed that DEGs between risk groups were primarily associated with chylomicron metabolism, among other pathways. Additionally, activated CD4+ T cells demonstrated the strongest positive correlation with risk scores, and most immune checkpoints showed significant differences between risk groups, with ASXL1 exhibiting the strongest correlation with risk scores. The Tumour Immune Dysfunction and Exclusion score was notably higher in the high-risk group. Moreover, in both the TCGA-LIHC and ICGC-LIRI-JP datasets, the expression of other prognostic features was elevated in tumour tissues, with the exception of CHST9. RT-qPCR confirmed the increased expression of TMCO3, RAP2A, ITGAV, ZFYVE26, and HMGN4. This study establishes a risk model for HCC based on seven crotonylation-associated prognostic features, offering a theoretical framework for the diagnosis and treatment of HCC.

Investigating SNHG3 as a potential therapeutic approach for HCC stem cells

IntroductionHepatocellular Carcinoma (HCC) is a common malignant tumor worldwide. Long Non-Coding RNA (lncRNA) has gained attention in tumor biology, and this study aims to investigate the role of lncRNA SNHG3 in HCC, specifically in the self-renewal and maintenance of liver cancer stem cells. MethodsThe expression of lncRNA SNHG3 was analyzed in HCC and adjacent normal tissue using the TCGA database. The expression levels of SNHG3 in HCC cell lines (Hep3B, HepG2, Huh7) were detected using qRT-PCR and Western blot techniques. Functional assays, including CCK-8, soft agar colony formation, and tumor sphere formation, were performed to evaluate the impact of SNHG3 on HCC stem cell functionality. MeRIP-qPCR was also used to investigate the regulatory role of SNHG3 in m6A modification of ITGA6 mRNA mediated by METTL3. ResultsThe study found that SNHG3 was significantly upregulated in HCC tissue and cell lines compared to normal liver tissue. SNHG3 expression correlated with the pathological stage, metastasis status, and tumor size of liver cancer. Inhibiting SNHG3 reduced proliferation, colony formation, and tumor sphere formation ability in HCC stem cells. SNHG3 also played a role in regulating the m6A modification and expression of ITGA6 through METTL3. ConclusionThis study emphasizes the upregulation of lncRNA SNHG3 and its role in HCC stem cell self-renewal. SNHG3 may regulate the m6A modification of ITGA6 mRNA through its interaction with METTL3, impacting the function of liver cancer stem cells. These findings support the potential of targeting SNHG3 as a therapeutic approach for HCC.

Potential use of SCAT1, SCAT2, and SCAT8 as diagnostic and prognosis markers in colorectal cancer

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Despite advancements, the underlying mechanisms controlling CRC's etiology remain unclear, and reliable biomarkers for diagnosis and treatment are still lacking. Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression, though many remain unidentified and their functions poorly understood. In this study, we investigated the expression of SCAT1, SCAT2, and SCAT8 lncRNAs in both cancerous and adjacent non-cancerous tissues from CRC patients. Using cDNA synthesized from total RNA extracted from 100 tissue samples, we performed Real-Time PCR to measure the expression levels of these lncRNAs. In addition, their diagnostic potential was evaluated through ROC curve analysis. Our results demonstrate that SCAT1, SCAT2, and SCAT8 are significantly upregulated in CRC tissues, with ROC analysis suggesting SCAT1 as a moderate biomarker and SCAT2 and SCAT8 as promising biomarkers for CRC diagnosis. Moreover, we found strong correlations between SCAT1 and SCAT8, as well as SCAT2 and SCAT8. Collectively, our findings indicate that SCAT1, SCAT2, and SCAT8 may act as oncogenes in CRC, offering potential as novel biomarkers for diagnosis and prognosis.

Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects on patients' FOXP1 and GGT levels

ObjectiveTo investigate the effect of capecitabine on the sensitivity of oxaliplatin and on the level of transcription factor forkhead box P1 (FOXP1) and gamma-glutamyl transpeptidase (GGT) in patients with intermediate and advanced gastric cancer. MethodsA total of 152 patients with intermediate and advanced gastric cancer diagnosed and treated in our hospital from April 2018 to May 2019 was selected as the research objects, and their clinical data were retrospectively analyzed. According to the different treatment methods, they were divided into the study group and the control group, with 76 cases in each group. The patients in the control group received with oxaliplatin, while the patients in the study group received with capecitabine on the basis of the control group. The therapeutic effect was evaluated according to the therapeutic effect evaluation criteria of solid tumors. The FOXP1 expression level in gastric cancer tissues was detected using immunohistochemistry. Serum levels of GGT were measured by chemiluminescence. The prognostic factors were analyzed by COX regression model, and the Kaplan-Meier survival curve was used to analyze the relationship between the influencing factors and the survival of gastric cancer. ResultsThe effective rate of capecitabine combined with oxaliplatin and oxaliplatin alone in the treatment of patients with intermediate and advanced gastric cancer were 94.74% and 76.32% respectively. Capecitabine enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin (P<0.05). Compared with adjacent normal tissues, the expression level of FOXP1 in gastric cancer tissues was lower (P<0.05). Before treatment, the expression of FOXP1 was low, and no significant difference was observed in the GGT level between the two groups (P>0.05). After treatment, the low expression rate of FOXP1 and serum GGT level were both significantly decreased, and those in the study group were lower than those in the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups (P>0.05). The 1-year survival rates of the study group and the control group were 90.79% and 78.95%, while the 3-year survival rates of the study group and the control group were 75.00% and 51.32%, respectively. Both the 1-year and 3-year survival rate of the study group was higher than that in the control group (P<0.05). The 1-year survival rate of 152 patients with gastric cancer was 84.87% (129/152) and the 3-year survival rate was 63.17% (96/152). Age, tumor diameter, tumor-node-metastasis (TNM) stage, lymph node metastasis, chemotherapy regimen and the expression of FOXP1 and GGT had significant effects on the survival rate (P<0.05). Gastric cancer patients with age < 60 years, TNM stage of Ⅰ ∼ Ⅱ, lymph node metastasis N0 ∼ N1, high expression of FOXP1, GGT < 387.2, and combined with drug chemotherapy had higher survival rate. ConclusionCapecitabine effectively enhanced the sensitivity of intermediate and advanced gastric cancer to oxaliplatin, improved the therapeutic effect, reduced the proportion of patients with low FOXP1 expression rate and serum GGT level, decreased the recurrence rate and ameliorated the prognosis of patients.This is a retrospective study, all data were analyzed retrospectively. This research was approved by the Ethics Review Committees of Fuwai Central China Cardiovascular Hospital (approval number: 2023-EC-015).

O-GlcNAcylation promotes malignancy and cisplatin resistance of lung cancer by stabilising NRF2.

The transcription factor NRF2 plays a significant role in regulating genes that protect cells from oxidative damage. O-GlcNAc modification, a type of posttranslational modification, is crucial for cellular response to stress. Although the involvement of both NRF2 and O-GlcNAc in maintaining cellular redox balance and promoting cancer malignancy has been demonstrated, the potential mechanisms remain elusive. The immunoblotting, luciferase reporter, ROS assay, co-immunoprecipitation, and immunofluorescence was used to detect the effects of global cellular O-GlcNAcylation on NRF2. Mass spectrometry was utilised to map the O-GlcNAcylation sites on NRF2, which was validated by site-specific mutagenesis and O-GlcNAc enzymatic labelling. Human lung cancer samples were employed to verify the association between O-GlcNAc and NRF2. Subsequently, the impact of NRF2 O-GlcNAcylation in lung cancer malignancy and cisplatin resistance were evaluated in vitro and in vivo. NRF2 is O-GlcNAcylated at Ser103 residue, which hinders its binding to KEAP1 and thus enhances its stability, nuclear localisation, and transcription activity. Oxidative stress and cisplatin can elevate the phosphorylation of OGT at Thr444 through the activation of AMPK kinase, leading to enhanced binding of OGT to NRF2 and subsequent elevation of NRF2 O-GlcNAcylation. Both in cellular and xenograft mouse models, O-GlcNAcylation of NRF2 at Ser103 promotes the malignancy of lung cancer. In human lung cancer tissue samples, there was a significant increase in global O-GlcNAcylation, and elevated levels of NRF2 and its O-GlcNAcylation compared to paired adjacent normal tissues. Chemotherapy promotes NRF2 O-GlcNAcylation, which in turn decreases cellular ROS levels and drives lung cancer cell survival. Our findings indicate that OGT O-GlcNAcylates NRF2 at Ser103, and this modification plays a role in cellular antioxidant, lung cancer malignancy, and cisplatin resistance.

Blood culture bottles meet the operating room: enhancing the diagnostic accuracy of infectious spondylitis through open microsurgical biopsy and intraoperative inoculation.

Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis.

The immunomodulatory role of the MAFB gene in hepatocellular carcinoma and its impact on biological activities

ObjectiveThe transcription factor MAFB is part of the MAF family and is known to promote hepatocellular carcinoma (HCC) by upregulating cyclin D1. However, its role in HCC immunity and prognosis remains unclear. This study explores the biological function, prognostic significance, and immune impact of MAFB in HCC. MethodsImmunohistochemistry was used to analyze MAFB expression in HCC and adjacent non-tumor tissues. RT-qPCR and Western blotting measured MAFB levels in HCC cell lines. Specific siRNA was used to knockdown MAFB in HCCLM3 and MHCC97H cells, followed by assays to evaluate cell proliferation, migration, and colony formation. Data from the TCGA database and online tools TIMER and TISDB were used to assess the relationship between MAFB and immune responses. A prognostic model based on MAFB-related immune genes was established, and drug sensitivity analysis was performed. ResultsMAFB was significantly overexpressed in HCC tissues. Knockdown of MAFB in HCC cell lines reduced their proliferation and migration abilities. The risk model based on MAFB-related immune genes effectively predicted patient prognosis, supported by ROC curves. Gene set enrichment analysis indicated that MAFB is involved in immune-related pathways. Several drugs were identified as potentially sensitive to MAFB expression levels. ConclusionMAFB plays a significant role in HCC development and immune regulation. The prognostic model combining MAFB-related immune genes provides valuable insights for predicting patient outcomes and identifying potential therapeutic targets.

EP.07F.04 Differences in High-Order, Three-Dimensional Chromatin Structure Between Tumor and Adjacent Normal Tissues in Lung Adenocarcinoma

EP.07F.04 Differences in High-Order, Three-Dimensional Chromatin Structure Between Tumor and Adjacent Normal Tissues in Lung Adenocarcinoma

Study on the expression of lncRNA PRKCA-AS1 in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most malignant tumors in the oral and maxillofacial region, with a poor prognosis. Previous studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in tumor development by regulating the biological behavior of various cancer cells. The aim of this study is to explore the role and potential mechanisms of lncRNA PRKCA-AS1 in OSCC. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of lncRNA PRKCA-AS1 in OSCC tissues and cell lines. Cell proliferation, migration and invasion were conducted to assess the biological functions of OSCC cell lines. The expression of lncRNA PRKCA-AS1 in OSCC tissues was higher compared to that of adjacent non-cancerous tissues, and its expression level was associated with the depth of tumor infiltration, lymph node metastasis, and tumor node metastasis (TNM) staging. Compared to the control group of normal human oral keratinocytes (HOK), the expression of lncRNA PRKCA-AS1 was also elevated in OSCC cell lines. Knockdown of lncRNA PRKCA-AS1 significantly affected the proliferation, migration, and invasion ability of OSCC cells. However, when lncRNA PRKCA-AS1 was further overexpressed, changes in cell proliferation and migration ability did not show statistical differences. LncRNA PRKCA-AS1 is highly expressed in OSCC, and its expression level is positively correlated with the depth of tumor infiltration, lymph node metastasis, and TNM staging. LncRNA PRKCA-AS1 is involved in regulating the proliferation, migration, and invasion of OSCC cells.

Bladder cancer associated with elevated heavy metals: Investigation of probable carcinogenic pathways through mitochondrial dysfunction, oxidative stress and mitogen-activated protein kinase

ObjectiveCarcinogenic mechanisms of heavy metals/ trace elements (HMTE) in bladder cancer (BC) are exactly unknown. Mitochondrial dysfunction (MD), oxidative stress (OS), and mitogen-activated protein kinases (MAPK) are probable carcinogenic mechanisms. The purpose is to investigate probable carcinogenic pathways of HMTE in BC using six MD genes, seven OS markers, and p38-MAPK. MethodsStudy included 125 BC/radical cystectomy (RC) patients between October 2020 and October 2022, and 72 controls. Exclusion criteria included previous neoplasm, chemo- or radiotherapy. Two samples (cancer/noncancer) were taken from RC specimens. Tissues/plasma/urine cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), strontium (Sr), aluminium (Al), zinc (Zn), boron (B) were measured by ICP-OES. Tissue MD genes (mt-CO3, mt-CYB, mt-ATP 6, mt-ATP8, mt-CO1, mt-ND1), and serum OS markers (8-OHdG, MDA, 3-NT, AGEs, AOPP, ROS, SOD2), p38-MAPK were assessed by RT-PCR, and ELISA, respectively. ResultsBC and adjacent tissue showed higher (Al, Co, Pb, Ni, Zn, Cd,Sr), lower B concentrations, compared to controls. High tissue concentrations (Cd, Co, Pb, Ni, Sr) were associated with higher MD genes, OS, MAPK and lower SOD2 levels. The same differences were greater in 41 patients with concomitant elevation of two or more HMTE. Noninclusion of BC-related oncogenes (e.g. RAS) is a limitation. ConclusionsEvidence suggests that high BC tissue (Cd, Co, Pb, Ni, Si) concentrations are associated with over-expressed MD genes, OS, p38-MAPK and low SOD2. These findings provide important understanding keys of probable carcinogenic pathways in BC associated with HMTE. So, efforts should be performed to minimize and counteract exposure to toxic HMTE.

Dissecting the Single-Cell Diversity and Heterogeneity Underlying Cervical Precancerous Lesions and Cancer Tissues.

The underlying cellular diversity and heterogeneity from cervix precancerous lesions to cervical squamous cell carcinoma (CSCC) is investigated. Four single-cell datasets including normal tissues, normal adjacent tissues, precancerous lesions, and cervical tumors were integrated to perform disease stage analysis. Single-cell compositional data analysis (scCODA) was utilized to reveal the compositional changes of each cell type. Differentially expressed genes (DEGs) among cell types were annotated using BioCarta. An assay for transposase-accessible chromatin sequencing (ATAC-seq) analysis was performed to correlate epigenetic alterations with gene expression profiles. Lastly, a logistic regression model was used to assess the similarity between the original and new cohort data (HRA001742). After global annotation, seven distinct cell types were categorized. Eight consensus-upregulated DEGs were identified in B cells among different disease statuses, which could be utilized to predict the overall survival of CSCC patients. Inferred copy number variation (CNV) analysis of epithelial cells guided disease progression classification. Trajectory and ATAC-seq integration analysis identified 95 key transcription factors (TF) and one immunohistochemistry (IHC) testified key-node TF (YY1) involved in epithelial cells from CSCC initiation to progression. The consistency of epithelial cell subpopulation markers was revealed with single-cell sequencing, bulk sequencing, and RT-qPCR detection. KRT8 and KRT15, markers of Epi6, showed progressively higher expression with disease progression as revealed by IHC detection. The logistic regression model testified the robustness of the resemblance of clusters among the various datasets utilized in this study. Valuable insights into CSCC cellular diversity and heterogeneity provide a foundation for future targeted therapy.

Resveratrol Inhibits Nasopharyngeal Carcinoma (NPC) by Targeting the MAPK Signaling Pathway.

With conventional cancer treatments facing limitations, interest in plant-derived natural products as potential alternatives is increasing. Although resveratrol has demonstrated antitumor effects in various cancers, its impact and mechanism on nasopharyngeal carcinoma remain unclear. This study aimed to systematically investigate the anti-cancer effects of resveratrol on nasopharyngeal carcinoma using a combination of experimental pharmacology, network pharmacology, and molecular docking approaches. CCK-8, scratch wound, and transwell assays were employed to confirm the inhibitory effect of resveratrol on the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. H&E and TUNEL stainings were used to observe the morphological changes and apoptosis status of resveratrol-treated cells. The underlying mechanisms were elucidated using a network pharmacology approach. Immunohistochemistry and Western blotting were utilized to validate key signaling pathways. Resveratrol inhibited the proliferation, invasion, and migration of nasopharyngeal carcinoma cells, ultimately inducing apoptosis in a time- and dose-dependent manner. Network pharmacology analysis revealed that resveratrol may exert its anti-nasopharyngeal carcinoma effect mainly through the MAPK pathway. Immunohistochemistry results from clinical cases showed MAPK signaling activation in nasopharyngeal carcinoma tissues compared to adjacent tissues. Western blotting validated the targeting effect of resveratrol, demonstrating significant inhibition of the MAPK signaling pathway. Furthermore, molecular docking supported its multi-target role with MAPK, TP53, PIK3CA, SRC, etc. Conclusion: Resveratrol has shown promising potential in inhibiting human nasopharyngeal carcinoma cells by primarily targeting the MAPK pathway. These findings position resveratrol as a potential therapeutic agent for nasopharyngeal carcinoma.

Role of inter- and extra-lesion tissue, transfer learning, and fine-tuning in the robust classification of breast lesions

Accurate and unbiased classification of breast lesions is pivotal for early diagnosis and treatment, and a deep learning approach can effectively represent and utilize the digital content of images for more precise medical image analysis. Breast ultrasound imaging is useful for detecting and distinguishing benign masses from malignant masses. Based on the different ways in which benign and malignant tumors affect neighboring tissues, i.e., the pattern of growth and border irregularities, the penetration degree of the adjacent tissue, and tissue-level changes, we investigated the relationship between breast cancer imaging features and the roles of inter- and extra-lesional tissues and their impact on refining the performance of deep learning classification. The novelty of the proposed approach lies in considering the features extracted from the tissue inside the tumor (by performing an erosion operation) and from the lesion and surrounding tissue (by performing a dilation operation) for classification. This study uses these new features and three pre-trained deep neuronal networks to address the challenge of breast lesion classification in ultrasound images. To improve the classification accuracy and interpretability of the model, the proposed model leverages transfer learning to accelerate the training process. Three modern pre-trained CNN architectures (MobileNetV2, VGG16, and EfficientNetB7) are used for transfer learning and fine-tuning for optimization. There are concerns related to the neuronal networks producing erroneous outputs in the presence of noisy images, variations in input data, or adversarial attacks; thus, the proposed system uses the BUS-BRA database (two classes/benign and malignant) for training and testing and the unseen BUSI database (two classes/benign and malignant) for testing. Extensive experiments have recorded accuracy and AUC as performance parameters. The results indicate that the proposed system outperforms the existing breast cancer detection algorithms reported in the literature. AUC values of 1.00 are calculated for VGG16 and EfficientNet-B7 in the dilation cases. The proposed approach will facilitate this challenging and time-consuming classification task.

The Prognostic Significance of CTSV Expression in Patients with Hepatocellular Carcinoma.

Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker. This study collected tumor and peritumoral archived specimens from 180HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV. In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC. CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.

Prognostic value of PLEKHA4 and its correlation with tumor-infiltrating immune cells in breast cancer: a comprehensive study based on bioinformatics and clinical analysis validation.

Pleckstrin homology containing family A, number 4 (PLEKHA4) plays a role in a number of biological processes in human cells, including cell polarization, growth, and proliferation. However, the relationship between PLEKHA4 expression and survival in breast cancer (BC) remains unclear. The aim of this study is to investigate the potential of PLEKHA4 as a prognostic indicator in BC. We obtained gene expression profiles of BC and normal tissues from the Tumor Immune Estimation Resource (TIMER), UALCAN web. Immunohistochemistry (IHC) staining was performed to investigate the protein expression and prognostic value of PLEKHA4 in BC patients. The prognostic value was analyzed using Kaplan-Meier curve analysis and Cox regression analysis in R software after downloading The Cancer Genome Atlas (TCGA) databases. The correlations between PLEKHA4 and tumor immune infiltrates were investigated via gene set variation analysis (GSVA). Signaling pathways related to PLEKHA4 expression were identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Both bioinformatics and IHC results showed that PLEKHA4 was expressed at low levels in BC tissues compared with the adjacent tissues. Furthermore, the expression of PLEKHA4 was negatively correlated with ages (χ2=6.394, P=0.01), molecular subtype (χ2=15.606, P=0.001), lymph node metastasis (χ2=13.753, P=0.004), tumor-node-metastasis (TNM) stage (χ2=22.616, P<0.001). Kaplan-Meier curves implicated low expression of PLEKHA4 was associated with worse survival of BC patients [hazard ratio (HR) =0.46, P=0.01]. Cox regression models showed that low PLEKHA4 expression could be an independent risk factor for BC (HR =0.911, P=0.006). The results of gene set enrichment analysis (GSEA) showed that cell cycle, Notch signaling pathway, nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, and Rho GTPases were highly enriched in the low PLEKHA4 expression group, as identified by GO and KEGG. Additionally, in BC, PLEKHA4 expression displayed a positive correlation with the infiltration of natural killer (NK) cells (P<0.001), CD8+ T cells (P<0.001), B cells (P<0.001), neutrophils (P<0.001), and dendritic cells (DCs) (P<0.001). The findings indicate that PLEKHA4 is an independent prognostic biomarker associated with key signaling pathways and immune infiltration in BC. Targeting PLEKHA4 may contribute to improving immunotherapy for BC.

Deciphering the PI3K-Akt pathway in lung cancer

This computational study explores the immune landscape of early-stage lung adenocarcinoma through single-cell RNA sequencing data analysis. By leveraging paired single-cell data, key insights were gained into the gene expression profiles of tumor samples, focusing on potential therapeutic targets and pathway interactions involved in cancer progression.Single-cell RNA sequencing data from non-lymphocytic immune cells isolated from stage IA lung adenocarcinoma and adjacent normal tissue were computationally processed. Data quality was assessed using sequence quality control tools, and reads were aligned to the hg38 reference genome. Differential gene expression analysis was conducted to identify upregulated and downregulated features. Reactome pathway analysis complemented with literature review was employed to scrutinize potential relationships and pathway interactions. Correlation analysis highlighted key genes involved in tumor progression, including Thrombospondin, HTR6 (5-hydroxytryptamine receptor 6), and LCK.Distinct gene expression patterns were identified in tumor samples, with strong positive correlations between Thrombospondin, HTR6, and LCK. These genes were found to interact within the PI3K-Akt pathway, suggesting their involvement in tumor proliferation and survival. Pathway analysis further revealed molecular crosstalk between these genes and other metabolic processes, offering potential avenues for therapeutic intervention.This computational analysis of single-cell RNA sequencing data identified key gene expression signatures and pathway interactions in early-stage lung adenocarcinoma. The findings, particularly the roles of Thrombospondin, HTR6, and LCK in the PI3K-Akt pathway, provide new insights into potential therapeutic targets for lung cancer treatment.