Clinicopathological Stage Research Articles

High expression of COX6B2 in gastric cancer is associated with poor long-term prognosis and promotes cell proliferation and cell cycle progression by inhibiting p53 signaling

To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients' long-term prognosis and its underlying mechanism. Based on the public databases and the medical records of patients, we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients. Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer. The effects of lentivirusmediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay, flow cytometry, and Western blotting. TCGA database and the results of immunohistochemistry, Western blotting and realtime PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues (P < 0.05). Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival (P < 0.05). A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage, CEA and CA19-9 (P < 0.05). A high expression of COX6B2, CEA level≥5 μg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients (P < 0.05), and COX6B2 expression level had a predictive value for long-term prognosis of the patients (P < 0.05). GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle. In the in vitro cell experiment, COX6B2 overexpression significantly promoted gastric cancer cell proliferation, increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21 (P < 0.05). s COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.

Role of exhaled hydrogen sulfide in the diagnosis of colorectal cancer

BackgroundColorectal cancer (CRC) is often accompanied by increased excretion of hydrogen sulfide (H2S). This study aimed to explore the value of exhaled H2S in the diagnosis of CRC.MethodsA total of...

Identification of potential biomarkers in follicular thyroid carcinoma: bioinformatics and immunohistochemical analyses

Abstract Objectives The prevalence of thyroid cancer has shown a progressive rise over time. This study aimed to explore the expression and underlying mechanisms of decorin (DCN) in follicular thyroid carcinoma (FTC), employing bioinformatics analysis and immunohistochemistry techniques. Methods The GSE27155 dataset was obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and core DEGs were identified through data mining and analysis using the R language and online databases. The expression of core DEGs was validated using The Cancer Genome Atlas database. Additionally, the correlation between DCN and clinicopathological stage, tumor-infiltrating lymphocytes, and hotspot molecules in thyroid cancer was assessed using the Gene Expression Profiling Interactive Analysis and TIMER databases. Immunohistochemical (IHC) analysis was then conducted to verify the differential expression of core DCN in FTC and adjacent tissues. Results We confirmed the downregulation of three DEGs (DCN, GPC3, and PDGFRA). Furthermore, the analysis revealed a significant association between DCN expression and the clinical stage of patients with thyroid cancer (p&lt;0.0001). DCN expression and the infiltration of several immune cells were positively correlated (p&lt;0.01). A significant positive correlation was also noted between DCN and the NRAS and KRAS genes (partial cor&gt;0, p&lt;0.05). Immunohistochemical analyses revealed a significantly lower staining score (3.071 ± 2.493) for DCN protein in cancer tissues than that in adjacent tissues (8.643 ± 2.094) (p&lt;0.0001). Conclusions DCN is underexpressed and contributes to tumor progression in FTC. Thus, DCN serves as a tumor suppressor gene in FTC and a promising therapeutic target.

Incorporating the 40-Gene Expression Profile (40-GEP) Test within Each Clinicopathologic Staging System Improves Metastatic Risk-Stratification in Patients Diagnosed with Cutaneous Squamous Cell Carcinoma (cSCC) and One or More High Risk Factors

Purpose: Three clinicopathologic-based risk assessment systems (Brigham and Women’s Hospital (BWH) staging, American Joint Committee on Cancer 8th Edition (AJCC8) staging or National Comprehensive Cancer Network (NCCN)) are used to guide treatment pathway decisions, including nodal assessment and adjuvant radiation therapy. Each of these systems suffers from accuracy limitations. The 40-GEP test was developed to use tumor biology to predict regional/distant metastasis and has previously been validated as an independent risk stratification test for cSCC patients who are diagnosed with one or more clinicopathologic risk factors. The purpose of this study was to evaluate the performance of the 40-GEP test in the prognostication of metastasis when results are used in the context of each of the clinicopathologic risk assessment system. Study: Under an IRB-approved protocol, centralized pathology review, and sample analysis were performed in a CAP-accredited, CLIA-certified laboratory using formalin-fixed paraffin-embedded archival primary SCC tumor specimens with one or more risk factors (n=897). Verified clinicopathologic information and outcomes data were collected from 58 contributing centers. Three-year risk stratification for regional and distant metastasis was assessed using Kaplan-Meier analysis for metastasis-free survival (MFS) for Class 1 (low risk), Class 2A (moderate risk), and Class 2B (high risk) groups. Nested Cox regression models and accuracy metrics were used to compare risk prediction of clinicopathologic risk assessment vs. clinicopathologic risk assessment in combination with 40-GEP. Results: The overall cohort had a metastasis rate of 13.2%, substantiating the high-risk status of this population. For the overall cohort, the 40-GEP test showed clinically and statistically significant differences in MFS rates between Class 1 (94.1%), Class 2A (81.1%), and Class 2B (56.8%) (p&lt;0.001, log-rank). Combining the results of the 40-GEP test with staging systems or NCCN risk categories led to increases in both NPV and PPV, indicating that a 40-GEP result improves the prediction of metastatic risk over the use of staging alone Table 1. Inclusion of 40-GEP with different clinicopathologic risk assessment methods (BWH and AJCC8, or NCCN risk subgroups) yielded significant improvements in prediction of metastatic events compared to each risk assessment method that did not include 40-GEP (ANOVA for deviance, p&lt;0.0001 for each comparison). Conclusions: Incorporating the 40-gene expression profile (40-GEP) test within each clinicopathologic risk assessment system improves risk-stratification, enabling more accurate treatment pathway decisions.

High Expression of THY1 in Intestinal Gastric Cancer as a Key Factor in Tumor Biology: A Poor Prognosis-Independent Marker Related to the Epithelial-Mesenchymal Transition Profile.

Gastric cancer (GC) is an important cancer-related death worldwide. Among its histological subtypes, intestinal gastric cancer (IGC) is the most common. A previous work showed that increased expression of the THY1 gene was associated with poor overall survival in IGC. Furthermore, it was shown that IGC tumor cells with high expression of THY1 have a greater capacity for tumorigenesis and metastasis in vitro. This study aimed to identify molecular differences between IGC with high and low expression of THY1. Using a feature selection method, a group of 35 genes were found to be the most informative gene set for THY1high IGC tumors. Through a classification model, these genes differentiate THY1high from THY1low tumors with 100% of accuracy both in the test subset and the independent test set. Additionally, this group of 35 genes correctly clustered 100% of the samples. An extensive validation of this potential molecular signature in multiple cohorts successfully segregated between THY1high and THY1low IGC tumors (>95%), proving to be independent of the gene expression quantification methodology. These genes are involved in central processes to tumor biology, such as the epithelial-mesenchymal transition (EMT) and remodeling of the tumor tissue composition. Moreover, patients with THY1high IGC demonstrated poor survival and a more advanced clinicopathological staging. Our findings revealed a molecular signature for IGC with high THY1 expression. This signature showed EMT and remodeling of the tumor tissue composition potentially related to the biology of IGC. Altogether, our results indicate that THY1high IGC tumors are a particular subset of tumors with a specific molecular and prognosis profile.

Management of melanoma: can we use gene expression profiling to help guide treatment and surveillance?

Although the incidence of cutaneous melanoma (CM) has been increasing annually, the mortality rate has been decreasing, likely due to better prevention, earlier detection, improved surveillance, and the development of new therapies. Current clinical management guidelines by the National Comprehensive Cancer Network (NCCN) are based on patient risk assignment using staging criteria established by the American Joint Committee on Cancer (AJCC). However, some patients with localized disease (stage I-II), generally considered to have a good prognosis, will develop metastatic disease and die, whereas some patients with later stage disease (stage III-IV) will be cured by surgery, adjuvant therapy, and/or systemic therapy. These results emphasize the importance of identifying patients whose risk may be over or underestimated with standard staging. Gene expression profile (GEP) tests are noninvasive molecular tests that assess the expression levels of a panel of validated genes, providing information about tumor prognosis, including the risk of recurrence, metastasis, and cancer-specific death. GEP tests can provide prognostic information beyond standard staging that may aid clinicians and patients in treatment and surveillance management decisions. This review describes how combining clinicopathologic staging with a robust assessment of tumor biology may provide information that will allow more refined intervention and long-term management.

FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression

BackgroundInvasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear.MethodsIn this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model.ResultsFAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs.ConclusionsIn this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.

Mir-21-5p and Mir-455-5p as Markers for Diagnosis and Prognosis of Rectal Adenocarcinoma may Reduce Local CD4+ and CD8+ Lymphocyte Infiltration.

This study aimed to verify miRNAs and the molecular mechanisms of diagnostic and prognostic biomarkers for rectal adenocarcinoma. Two miRNA datasets of rectal adenocarcinoma were obtained from GEO and TCGA. GEO2R tool, Venn diagram, Kaplan-Meier survival analysis, KEGG pathway analyses, DIANA TOOLS, and Wilcoxon rank-sum test were used for biological information analysis. The diagnostic utility of miRNAs and immune infiltration of tumors in Chinese patients were validated by RTqPCR and immunofluorescence analysis. MiR-21-5P and miR-455-5p were both found to have a significant correlation with poor prognosis and higher expression in rectal adenocarcinoma. Besides, the ability to prognosis was independent of the clinicopathological stage. MiR-21-5P and miR-455-5p were enriched in the TGF-beta, Wnt, MAKP, and PI3K-AKT signaling pathways. Meanwhile, the high expression phenotype of miR-21-5P and miR-455-5p decreased CD4+ and CD8+ T cells. In summary, we found two significant diagnostic and prognostic miRNAs of rectal adenocarcinoma via integrated bioinformatics approach and clinical trials, which might decrease CD4+ and CD8+ T cells.

A Cost-Effective, Machine Learning-Based New Unified Risk-Classification Score (NU-CATS) for Patients with Endometrial Cancer

Treatment for endometrial cancer (EC) with radiotherapy is increasingly guided by molecular risk classifications. Derived from genomic profiling of The Cancer Genome Atlas (TCGA) project, several EC risk classification systems, including ProMisE and Leiden/TransPORTEC, have been developed. However, the current systems were developed on a relatively homogeneous population. Black or African American (BOAA) patients have consistently been demonstrated to have worse stage-adjusted prognosis than Caucasians. Given this, we intended to develop a new unified risk classification system (NU-CATS) for EC patients using machine learning (ML) utilizing datasets with demographically diverse populations. TCGA-Uterine Corpus Endometrial Carcinoma (n = 596), Memorial Sloan Kettering-Metastatic Events and Tropisms (MSK-MET, n = 1,315) and the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (AACR-GENIE, n = 4,561) were used to identify genetic alterations and clinicopathological features, including age, race, stage, histologic grade and features, and distribution of metastatic disease. Software packages including Keras, Pytorch, and Scikit Learn were tested to build artificial neural networks (ANNs) with a binary output as either intra-abdominal metastatic lesions vs. non-metastatic. A 5-layered ANN (5-6-4-2-1) using 5 inputs ('age at surgery', 'histology', 'race', 'mismatch repair status' and 'TP53'). The optimal performing ANN was selected and cross validated. The weights and biases of the trained ANN were used to reconstruct the algorithm. BOAA patients with EC have worse prognosis than Caucasians, adjusting for TP53 or POLE mutation status. TP53 is the most common gene differentially altered by race in EC. Over 75% of BOAA patients carry TP53 mutations as compared to approximately 40% of Caucasians. Older age is associated with an increasing likelihood of TP53 mutations, high risk histology, and distant metastasis. For patients above age 70, 91% of BOAA and 60% of Caucasian EC patients carry TP53 mutations. The NU-CATS that incorporates age, race, histology, mismatch repair (MMR) status, and TP53 mutation status showed 75% accuracy in prognosticating intra-abdominal metastasis. A higher NU-CATS (>50) is associated with about 2-fold increased risk of having positive pelvic or para-aortic lymph nodes (LNs) and distant. NU-CATS was shown to outperformed TransPORTEC model for estimating risk of FIGO Stage I/II disease progression and survival in BOAA EC patients. Despite adjusting for molecular classification, race and age retain prognostic importance in EC. NU-CATS, a ML-based, cost-effective algorithm, incorporates diverse clinicopathologic and molecular variables of EC, and yields superior prognostication of the risk of nodal involvement, distant metastasis, disease progression, and overall survival as compared to other classification systems.

Skin cancer characteristics during the first year of the COVID-19 pandemic at a tertiary hospital in Latin America.

The influence of the novel human coronavirus disease (COVID-19) pandemic on skin cancer characteristics in Latin America is still poorly elucidated. This was a cross-sectional study which included patients diagnosed with skin cancer (basal cell carcinoma [BCC], cutaneous squamous cell carcinoma [cSCC], and primary cutaneous melanoma [cMM]) during the first year of the COVID-19 pandemic (from March 1, 2020, to February 28, 2021) and the preceding year at our institution. The total number of skin cancer diagnoses and surgeries, as well as their topography, clinicopathological staging at diagnosis, and treatment delay were compared between the two periods. There was a 31.8% reduction in skin cancer diagnoses during the first year of the COVID-19 pandemic at our institution. There was an increase in the proportion of low-risk cancers according to the NCCN guidelines for BCCs (40.8-49%, P < 0.001) and cSCCs (41.7-49.6%, P = 0.03), but there was no difference in the distribution of other staging systems for the three types of cancer. We also found a significant reduction in surgeries for BCCs (-57.6%, P < 0.001) and cSCCs (-44.7%, P < 0.001) but not for cMM. The first year of the COVID-19 pandemic was associated with reduced numbers of skin cancer diagnoses and surgeries at our institution. This study provides an assessment of skin cancer characteristics during the first year of the pandemic in the Latin American population.

Safety and efficacy of tislelizumab plus chemotherapy as preoperative treatment in potentially resectable locally advanced non-small-cell lung cancer patients.

Locally advanced non-small-cell lung cancer (LA-NSCLC) requires more preoperative regiments in the era of immunotherapy. Tislelizumab was approved for first-line treatment for advanced lung cancer, bringing hope for preoperative therapy in LA-NSCLC. The aim of this study was to investigate the safety and efficacy of preoperative tislelizumab plus chemotherapy in LA-NSCLC. The medical records at the First Affiliated Hospital of Zhejiang University were examined retrospectively from September 2019 to June 2022 for this descriptive single-arm cohort study. Patients with LA-NSCLC were treated with tislelizumab plus platinum-based dual-drug regimens for 2-6 cycles and regular imaging assessments were performed every 1-2 cycles. Data including demographic characteristics, clinicopathological staging, adverse events and surgery-related details were recorded in specifically designed forms. Forty patients met the inclusion criteria of the study and 23 patients underwent curative intent surgeries. Significantly clinical and pathological downstaging was observed, with the objective response rate being 65.00%, leading to a major pathological remission (MPR) rate of 56.52% and a pathological complete remission (pCR) rate of 34.78%. Grade 3-4 treatment-related adverse events occurred in 4 patients and no perioperative death occurred. The 1-year progress-free survival rate and the 1-year overall survival rate were 85.0% and 90.0%, respectively. Tislelizumab plus chemotherapy as preoperative therapy demonstrates promising antitumour activity for potentially resectable LA-NSCLC with high MPR, pCR and acceptable toxicity and survival.

Comprehensive pan-cancer analysis of expression profiles and prognostic significance for NUMB and NUMBL in human tumors.

NUMB has been initially identified as a critical cell fate determinant that modulates cell differentiation via asymmetrical partitioning during mitosis, including tumor cells. However, it remains absent that a systematic assessment of the mechanisms underlying NUMB and its homologous protein NUMBLIKE (NUMBL) involvement in cancer. This study aimed to investigate the prognostic significance for NUMB and NUMBL in pan-cancer. In this study, using the online databases TIMER2.0, gene expression profiling interactive analysis, cBioPortal, the University of ALabama at Birmingham CANcer data analysis Portal, SearchTool for the Retrieval of Interacting Genes/Proteins, and R software, we focused on the relevance between NUMB/NUMBL and oncogenesis, progression, mutation, phosphorylation, function and prognosis. This study demonstrated that abnormal expression of NUMB and NUMBL were found to be significantly associated with clinicopathologic stages and the prognosis of survival. Besides, genetic alternations of NUMB and NUMBL focused on uterine corpus endometrial carcinoma, and higher genetic mutations of NUMBL were correlated with more prolonged overall survival and disease-free survival in different cancers. Moreover, S438 locus of NUMB peptide fragment was frequently phosphorylated in 4 cancer types and relevant to its phosphorylation sites. Furthermore, endocytosis processing and neurogenesis regulation were involved in the functional mechanisms of NUMB and NUMBL separately. Additionally, the pathway enrichment suggested that NUMB was implicated in Hippo, Neurotrophin, Thyroid hormone, and FoxO pathways, while MAPK, Hippo, Rap1, mTOR, and Notch pathways were related to the functions of NUMBL. This study highlights the predictive roles of NUMB and NUMBL in pan-cancer, suggesting NUMB and NUMBL might be served as potential biomarkers for diagnosis and prognosis in various malignant tumors.

Circular RNA hsa_circ_0049657 as a Potential Biomarker in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.

Results of robot-assisted minimally invasive esophagectomy in 111 consecutive patients: an Asia cohort study

BackgroundRobot-assisted minimally invasive esophagectomy (RAMIE) is becoming increasingly popular as a treatment for esophageal cancer. The purpose of this study was to use the da Vinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA) to perform 111 consecutive cases of radical esophageal cancer and report the perioperative data of surgery and postoperative complications and short-term oncological outcomes.MethodsWe retrospectively analyzed 111 patients who underwent RAMIE conducted at Fujian Medical University Union Hospital from August 2016 to January 2021. Each patient’s characteristics, clinicopathological stage, postoperative pathological stage, surgery outcome, postoperative recovery, and short-term oncological outcomes were analyzed.ResultsOf the 111 patients who underwent RAMIE, 77 were male and 34 were female, and the mean age was 62.1 ± 8.8 years. Twenty-seven patients (24.3%) received preoperative neoadjuvant therapies, the most popular of which was preoperative induction chemotherapy in 16 cases (14.4%), followed by preoperative induction radiotherapy in 8 cases (7.2%) and preoperative induction chemotherapy plus immunization in 3 cases (2.7%). The vast majority of patients (110/111, 99.1%) underwent radical resection, with a mean intraoperative bleeding amount of 99.9 ± 68.4 mL and a mean operative time of 271.9 ± 70.0 min. The mean total number of lymph nodes removed was 40.9 ± 16.7, including 21.8 ± 9.0 thoracic lymph nodes. Fifty-five (49.6%) patients had lymph node metastases, including 17 (15.3%) with lymph node metastases in the left recurrent laryngeal nerve, 24 (21.6%) with lymph node metastases in the right recurrent laryngeal nerve, and 7 (6.3%) with lymph node metastases in the bilateral recurrent laryngeal nerve. The positive rate of left recurrent nerve lymph nodes was 4.77%, and he positive rate of right recurrent nerve lymph nodes was 8.38%. The main postoperative complications included pulmonary infection in 24 cases (21.6%), celiac disease in 3 cases (2.7%), tracheoesophageal fistula in 1 case (0.9%), anastomotic fistula in 3 cases (2.7%), postoperative cardiac arrhythmias in 11 cases (9.9%), VTE in 3 cases (2.7%), and pleural effusion (requiring postoperative tube drainage) in 13 cases (11.7%). Additionally, 2 cases of postoperative pneumothorax (1.8%), 1 case of poor incision healing (0.9%), 1 case of incomplete bowel obstruction (0.9%), 1 case of neck hematoma (0.9%), and 1 case of postoperative admission to the intensive care unit (0.9%) occurred. The median length of stay was 10.9 ± 6.1 days, and there were no cases of perioperative death.ConclusionsRobotic esophageal cancer radical surgery is safe and feasible. The surgeon can be proficient in thoracic robotic surgery and mediastinal lymph node dissection and achieve high levels of perioperative safety and short-term efficacy.

CLEC11A expression as a prognostic biomarker in correlation to immune cells of gastric cancer.

Gastric cancer (GC) is a prevalent malignant cancer characterized by a poor survival rate. The C-type lectin domain family 11 member A (CLEC11A) is part of the C-type lectin superfamily, and its dysregulation has been implicated in the progression of several cancers. The specific role of CLEC11A and its association with immune infiltration in GC, however, remains unclear. In this study, we employed The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, Tumor IMmune Estimation Resource (TIMER) database, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier plotter databases, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and the CIBERSORT algorithm to investigate CLEC11A expression, its prognostic significance, its association with tumor immune infiltration, and gene function enrichment in GC. We conducted western blotting, Cell Counting Kit-8 (CCK-8), wound healing, and transwell assays to validate CLEC11A's function. We found that CLEC11A expression was significantly elevated in GC when compared to adjacent non-tumor tissues. Elevated CLEC11A expression was strongly associated with poor survival outcomes and advanced clinicopathological stages. Moreover, heightened CLEC11A expression positively correlated with immunomodulators, chemokines, and the infiltration of immune cells, especially M2 macrophages, in GC. Additionally, CLEC11A silencing suppressed GC cells proliferation, migration and invasion in vitro. Our results elucidate the functions of CLEC11A in GC, suggesting its potential as a valuable prognostic biomarker and therapeutic target for GC immunotherapy.

The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer

PurposeAs a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms.MethodsBioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts.ResultsHere, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance.ConclusionThese findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

Presymptomatic and early pathological features of MAPT-associated frontotemporal lobar degeneration

Early pathological features of frontotemporal lobar degeneration (FTLD) due to MAPT pathogenic variants (FTLD-MAPT) are understudied, since early-stage tissue is rarely available. Here, we report unique pathological data from three presymptomatic/early-stage MAPT variant carriers (FTLD Clinical Dementia Rating [FTLD-CDR] = 0–1). We examined neuronal degeneration semi-quantitatively and digitally quantified tau burden in 18 grey matter (9 cortical, 9 subcortical) and 13 white matter (9 cortical, 4 subcortical) regions. We compared presymptomatic/early-stage pathology to an intermediate/end-stage cohort (FTLD-CDR = 2–3) with the same variants (2 L315R, 10 P301L, 6 G272V), and developed a clinicopathological staging model for P301L and G272V variants. The 68-year-old presymptomatic L315R carrier (FTLD-CDR = 0) had limited tau burden morphologically similar to L315R end-stage carriers in middle frontal, antero-inferior temporal, amygdala, (para-)hippocampus and striatum, along with age-related Alzheimer’s disease neuropathological change. The 59-year-old prodromal P301L carrier (FTLD-CDR = 0.5) had highest tau burden in anterior cingulate, anterior temporal, middle/superior frontal, and fronto-insular cortex, and amygdala. The 45-year-old early-stage G272V carrier (FTLD-CDR = 1) had highest tau burden in superior frontal and anterior cingulate cortex, subiculum and CA1. The severity and distribution of tau burden showed some regional variability between variants at presymptomatic/early-stage, while neuronal degeneration, mild-to-moderate, was similarly distributed in frontotemporal regions. Early-stage tau burden and neuronal degeneration were both less severe than in intermediate-/end-stage cases. In a subset of regions (10 GM, 8 WM) used for clinicopathological staging, clinical severity correlated strongly with neuronal degeneration (rho = 0.72, p < 0.001), less strongly with GM tau burden (rho = 0.57, p = 0.006), and did not with WM tau burden (p = 0.9). Clinicopathological staging showed variant-specific patterns of early tau pathology and progression across stages. These unique data demonstrate that tau pathology and neuronal degeneration are present already at the presymptomatic/early-stage of FTLD-MAPT, though less severely compared to intermediate/end-stage disease. Moreover, early pathological patterns, especially of tau burden, differ partly between specific MAPT variants.

Nomogram based on clinical characteristics for predicting overall survival in gastric cancer patients with preoperative anemia.

Preoperative anemia is associated with increased postoperative morbidity and mortality and increased perioperative transfusion risk. For surgical patients, this affects physical and cognitive ability and quality of life, but it is an important and modifiable risk factor. To determine the effect of preoperative anemia on the prognosis of gastric cancer (GC) patients and generate a prognostic nomogram to predict the postoperative overall survival (OS) of GC patients with preoperative anemia. Clinicopathological and follow-up data of GC patients treated at Zhejiang Provincial People's Hospital (China) from 2010 to 2015 were collected. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. Then, these factors were used to construct a nomogram to predict 1-, 3-, and 5-year postoperative OS in preoperative anemic GC patients. The nomogram was assessed by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Nine hundred and sixty GC patients were divided into two groups (preoperatively anemic and nonanemic), and postoperative survival analysis was performed on both groups, yielding a shorter postoperative survival for preoperatively anemic patients than for nonanemic patients. A total of 347 GC patients with preoperative anemia were included. Age, preoperative alpha-fetoprotein level, monocyte count, lymphocyte count, clinicopathological stage, liver metastasis, and GC type were identified as independent prognostic factors for OS. The area under the ROC curve (AUC) of the nomogram for predicting 1-, 3-, and 5-year OS was 0.831, 0.845, and 0.840, respectively, for the training cohort, and the corresponding AUC values in the validation cohort were 0.827, 0.829, and 0.812, respectively. Calibration curves and DCA indicated good performance of the nomogram. In all, we have successfully produced and verified a useful nomogram for predicting OS in GC patients with preoperative anemia. This nomogram based on a variety of clinicopathological indices can provide an effective prognostic assessment and help clinicians choose an appropriate treatment strategy for GC patients with preoperative anemia.

Systematic analysis of the prognosis and immune infiltration of E2Fs in thyroid carcinoma.

Purpose: To evaluate the diagnostic and prognostic utility of E2F transcription factors (E2Fs) in thyroid carcinoma (THCA) and their association with immune infiltration. Methods: The transcription and protein levels of E2Fs in THCA tissues were examined using the R language and the Human Protein Atlas (HPA) database in this research. We utilized the UALCAN and GEPIA2 databases to analyze the association between the level of E2Fs and the clinicopathological features of THCA. The prognostic utility of E2F expression in THCA was studied using the R language and the Gene Set Cancer Analysis (GSCA) database. Over-representation analysis (ORA) and gene set enrichment analysis (GSEA) were employed to analyze the effect of E2F family members. The TISIDB database and Tumor Immune Estimation Resource (TIMER) database were utilized to investigate the relationship between E2F expression and the level of immune infiltration in thyroid cancer. Results: E2Fs are highly conserved in thyroid carcinoma and rarely mutated. E2Fs are strongly expressed in THCA and are highly related with the clinicopathological stage of THCA. Patients with THCA have a poor prognosis when E2Fs are highly expressed. The function of E2Fs in THCA may be closely related to the renin-angiotensin system (Ras) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, apoptosis, and immune response. With regard to the immune infiltration, E2F expression and tumor-infiltrating lymphocytes exhibited a positive connection. Conclusion: The level of E2Fs is connected with the prognosis and immune infiltration level in THCA, revealing that E2Fs may be a prognostic and immune infiltration cell marker in THCA patients.

Clinicopathological characteristics and postoperative prognosis of patients with nuclear pedigree of esophageal squamous cell carcinoma.

The aim of this work is to analyze the clinicopathological characteristics and prognostic factors of patients with nuclear pedigree of esophageal cancer. The clinicopathological data and follow-up information of 3,260 patients from different nuclear pedigree of esophageal cancer who underwent radical resection of esophageal cancer were collected, and the clinicopathological characteristics and prognostic factors of the patients were analyzed. The male to female ratio of 3,260 patients with esophageal cancer was 1.7:1. The diagnosis age was ranged from 32 to 85 (60.2 ± 8.1) years old. About 53.8% of the patients were ≥ 60 years old; About 88.8% of the patients came from the high incidence area of esophageal cancer; About 82.5% of the tumors were located in the middle and lower segments of esophagus; Poor, moderate and well differentiation accounted for 26.6%, 61.9% and 11.5% respectively; The surgical margin accounted for 94.3%; 47.6% of the tumors were shorter than 4cm in length; Clinicopathological TNM stage (0+I) accounted for 15.2%, and stage II, III and IV accounted for 54.5%, 29.9% and 0.4%, respectively. Cox analysis showed that male, diagnosed age ≥ 60 years, tumor located in neck and upper esophageal segments, poor differentiation, tumor length ≥ 4cm, and advanced TNM were independent risk factors for the prognosis of patients in nuclear pedigree with esophageal cancer. Gender, diagnosis age, tumor location, degree of differentiation, tumor length and TNM stage are the influencing factors for the prognosis of patients with nuclear pedigree of esophageal cancer, which will provide important data for the future study of esophageal cancer family aggregation.