International journal of clinical and experimental pathology最新文献

Objective: Mutations or aberrant expression of genes in an organism tend not to be completely random and this cumulative effect predisposes to the development of malignant tumours. This study aims to reveal the possible aberrant expression of high frequency mutated genes, and then to investigate their role in development, prognosis, signalling pathway function and drug resistance in breast cancer.

Methods: The mutated genes in breast cancer (BRCA) clinical samples were identified and detected by high-throughput sequencing. High-frequency mutant genes were counted. Gene expression profiles and the relationship with prognosis were analysed throughout TCGA database. qRT-PCR was used to analyse the mRNA levels of the six high-frequency mutant genes in BRCA tissues and cell lines. IHC was used to analyse the protein levels of the six high-frequency mutant genes in BRCA tissues. The linear interaction, single-cell layer clustering status and the influence in immune cell infiltration degree among these six high-frequency mutant genes were analysed by bioinformatics analysis. The STITCH and cMAP datasets were used for high-frequency mutant gene interaction networks, association signalling pathway enrichment and drug-transcriptome analyses. The effects of trastuzumab on the proliferative capacity of breast cancer cells, as well as on the expression of six high-frequency mutated genes were determined by CCK8 assay.

Results: The genes that were statistically found to have high-frequency mutations in the samples recruited in the present study by high-throughput sequencing analysis included TP53, PIK3CA, NF1, TBX3, BRCA1 and BRCA2. The expression profiles of these genes and the correlation with prognosis were further demonstrated using the TCGA database: the trend in this study was similar to that of BRCA in TCGA. The mRNA and protein expression of these genes showed that the expression of TP53, NF1, TBX3, BRCA1 and BRCA2 was higher in tumor samples than that in normal samples, with an opposite trend for PIK3CA, a similar trend was observed in BRCA cell lines. The protein expressions of TP53, NF1, TBX3, BRCA1 and BRCA2 displayed the same trend by IHC. Other correlation results include 1) the single cell layer clustering of these six genes resulted in significant clustering with few overlapping regions; 2) these six genes showed different degrees of influence on BRCA immune cell infiltration; 3) these six genes showed a significant correlation between each other; 4) the network of each gene had partially overlapping molecules; and 5) the PI3K pathway was a key association pathway in BRCA. Finally, the cell proliferation ability results confirmed the optimal concentration of trastuzumab and its effect on mRNA expression of these six genes.

Non-invasive papillary urothelial carcinomas present as cytoarchitectural disorders without invasion through the basement membrane. They are divided into low-grade and high-grade categories on the basis of the extent of cytologic atypia and architectural disarray. Notably, divergent differentiation (such as squamous and glandular differentiation) and variants (such as nested, micropapillary, plasmacytoid, and sarcomatoid) are reported primarily in invasive and high-grade urothelial carcinomas. We present two cases of low-grade non-invasive papillary urothelial carcinoma with recently described whorled features (urothelial eddies). Both patients were 77-year-old males with small papillary lesions in the bladder. Histopathologic examination revealed low-grade non-invasive papillary urothelial carcinoma with a sporadic whorled pattern. Patient number 1's tumor exhibited cytokeratin (CK) 20 immunopositivity, up to 5% Ki-67 labeling, and wild-type p53 staining. Patient number 2's tumor was negative for CK20 with wild type p53 staining in portions with whorls, but demonstrated diffuse CK20 and extensive p53 staining (possible mutation) in tumor portions lacking whorls. Patient number 1 experienced a 14-month recurrence and a second possible recurrence 43 months after the initial diagnosis. Patient number 2 experienced recurrence of low-grade papillary urothelial carcinoma with focal whorls in one location and subsequently a distinct low-grade papillary urothelial carcinoma with whorled features in a different part of the bladder. Our limited study supports the reported association of rare whorled features with non-invasive low-grade papillary urothelial carcinoma, albeit with a diverse immunophenotype. Evaluation of both whorled and non-whorled areas in the histology along with CK20 and p53 staining may be helpful for complete diagnostic and prognostic evaluation of these cases.

Objective: To explore the characteristics of the ploidy status of Small Cell Lung Cancer (SCLC) cells and assesses its efficacy in cytopathological diagnosis of SCLC.

Methods: A retrospective analysis was performed on patients who agreed to DNA image cytometry (DNA ICM) and serum tumor biomarker testing. Samples for ploidy assessment, all from bronchial procedures, were analyzed using DNA ICM. Data on demographic features, pathological characteristics, staging results, biomarkers such as neuron specific enolase (NSE) and Pro-gastrin-releasing peptide (ProGRP) data, and ploidy status across different groups were collected. Corresponding statistical analyses were conducted to examine differences in aneuploid status among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of DNA ICM and tumor markers for diagnosing SCLC.

Results: A total of 74 patients with SCLC, 108 patients with NSCLC, and 74 patients with benign lesions were included. The age range of all patients was 26 to 85 years, with 69% being male and 31% female. In terms of ploidy status, single aneuploid cell peaks and double aneuploid peaks were observed in both SCLC and NSCLC groups. The proportions of two types of aneuploid cell peaks differed significantly between the two groups (P=0.008). The aneuploid cell ratio showed a high accuracy for small-cell lung cancer, with a sensitivity of 91.2% and a specificity of 88.1%. There was no statistical difference in ploidy status between limited and extensive stages of SCLC. As for biomarkers, the AUC (area under the curve) values were 0.921 for NSE and 0.928 for ProGRP, with a significant difference in NSE between two stages of SCLC (P=0.015), while no significant difference was observed in ProGRP.

Conclusion: Aneuploid cell peaks in SCLC patients are mostly distributed in the near triploid range, possibly serving as a specific cytological marker for SCLC. DNA ICM is a highly sensitive tool that may be an adjunct for SCLC diagnosis.

Introduction: Ischemic Stroke (IS) is characterized by complex molecular alterations involving disruptions in lipid metabolism and immune interactions. However, the roles of lipid metabolism-associated genes in the pathogenesis of IS through immune regulation interaction are rarely explored. In this study, we aimed to explore the intricate correlation between lipid metabolism-associated immune changes and IS through a machine-learning algorithm.

Materials and methods: We downloaded the GSE16561, GSE22255, and GSE37587 datasets from NCBI. Using the GSE16561 dataset, we analyzed differential gene expression profiles related to lipid metabolism with the "Limma" R package. We constructed a diagnostic model employing techniques such as Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression and Random Forest (RF), which was further validated using the independent GSE22255 and GSE37587 datasets. Correlations between model genes and immune cell percentages were examined by Spearman analysis. We further validated the diagnostic value of these model genes in 28 clinical samples using RT-qPCR.

Results: We identified 26 lipid metabolism genes with significant expression disparities between normal and diseased groups, closely linked to immune cell populations. Seven signature genes (ACSS1, ADSL, CYP27A1, MTF1, SOAT1, STAT3, and SUMF2) were identified using LASSO and RF algorithms for a potential diagnostic model, effectively distinguishing healthy and IS samples in both training and validation (AUC = 0.725) datasets. The mRNA expression levels of these model genes were further validated as a blood biomarker for IS patients in our clinical samples. Single-cell analysis further revealed high expression of Cyp27a1 in dendritic cells and macrophages, and decreasing expression of Soat in progenitor cells as the disease progressed. The expression of Stat3 in most immune cells was upregulated in progenitor cells as the disease progressed. Additionally, a regulatory network identified transcription factors regulating genes such as STAT3.

Conclusion: This study identified novel lipid metabolism biomarkers for IS, enhancing our understanding of IS by shedding light on lipid metabolism and immune interactions. This may facilitate innovative diagnostic approaches to IS.

Targeted therapies are effective in non-small cell lung cancer (NSCLC) patients with driver gene mutations. Chemotherapy combined with immunotherapy is also a common treatment strategy in lung cancer. However, in previous studies, patients with ALK (Anaplastic Lymphoma Kinase) rearranged had a low response to immune checkpoint inhibitor (ICI) and the role of immunotherapy in ALK-positive NSCLC patients is unclear. Here, we report a case of a young man with ALK rearranged who demonstrated a complete response to anti-PD1 combination with chemotherapy, which suggests some ALK-rearranged patients with high expression of PD-L1 may permanently benefit from immunotherapy.

Objective: Ischemic stroke (IS) is a major public health concern worldwide. In this study, we aimed to investigate the relationship between ABCB1 gene polymorphisms and antiplatelet resistance in patients with IS.

Methods: We performed a comprehensive search of the PubMed, China National Knowledge Infrastructure, Web of Science, and WANFANG databases for articles published until February 2024. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the association between ABCB1 polymorphisms and antiplatelet resistance in patients with IS. All the statistical analyses were performed using STATA version 11.0.

Results: Eleven studies containing 2,228 cases and 2,556 controls met the inclusion criteria. Our results showed that aspirin resistance in patients with IS was significantly correlated with the polymorphism of ABCB1 rs1045642 (Allele model: OR=1.5, 95% CI [1.10, 2.05], P=0.010; Homozygote model: OR=2.02, 95% CI [1.01, 4.05], P=0.047; Heterozygote model: OR=1.37, 95% CI [0.91, 2.08], P=0.132; Dominant model: OR=1.75, 95% CI [1.09, 2.81], P=0.021; Recessive model: OR=1.61, 95% CI [1.01, 2.57], P=0.045). Meanwhile, we found that ABCB1 rs1045642 polymorphism might be significantly associated with clopidogrel resistance in IS (A. Homozygote model: OR=3.35, 95% CI [1.99, 5.63], P=0.000; B. Heterozygote model: OR=0.81, 95% CI [0.54, 1.21], P=0.895; C. Dominant model: OR=1.41, 95% CI [0.59, 3.36], P=0.435; D. Recessive model: OR=3.43, 95% CI [2.14, 5.51], P=0.000).

Conclusion: This meta-analysis suggests a potential link between ABCB1 rs1045642 polymorphism and resistance to clopidogrel or aspirin in patients with IS.

[This corrects the article on p. 1453 in vol. 11, PMID: 31938243.].

Female adnexal tumor of probable Wolffian origin (FATWO) is a rare gynecologic tumor. We describe a case of 53-year-old female patient in whom an adnexal mass was found. Microscopic examination revealed that the tumor arose in the adnexal soft tissue, composed of bland cells with an admixture of solid and sieve-like patterning, while presenting a high mitotic activity. Tumor cells were positive for Vimentin, CD10, and hormone receptors, while showing variable expression for sex cord-stromal markers, and was negative for GATA binding protein 3 (GATA-3), and thyroid transcription factor 1 (TTF1). The definitive diagnosis was FATWO. Subsequently, we conducted next-generation sequencing (NGS) in this case, and a CTNNB1 (c.98C>G, p.S33C) mutation was detected. The patient underwent tumor resection, hysterectomy, and bilateral adnexectomy, followed by annual computed tomography scans for monitoring. No evidence of recurrence or metastasis was observed at the 2-year postoperative follow-up. To the best of our knowledge, this is the fourth study having performed NGS on a FATWO. To further elucidate this rare neoplasm and improve the accuracy of diagnosis, we conducted a comparative analysis of the clinicopathological, immunohistochemical, and molecular features of our case with those previously reported in the literature, subsequently discussing the differential diagnosis.

[This corrects the article on p. 2818 in vol. 7, PMID: 25031701.].

Objective: Gastric cancer (GC) is a highly prevalent malignancy, yet its early diagnosis rate is generally low. Therefore, we have established a serum-based combined detection method based on tumor autoantibodies aimed at improving the diagnostic rate of gastric cancer.

Methods: Through clinical studies, we selected a series of proteins aberrantly expressed in gastric cancer patients, including RalA, Survivin, NY-ESO-1, p53, Cyclin B1, and Koc, and expressed and purified them using prokaryotic expression and nickel column chromatography.

Results: The levels of autoantibodies in the serum of gastric cancer patients and healthy individuals were measured using enzyme-linked immunosorbent assay (ELISA), and the diagnostic value of the combined detection of tumor autoantibodies for gastric cancer was evaluated through receiver operating characteristic (ROC) curve analysis. The levels of autoantibodies against RalA, Survivin, NY-ESO-1, p53, and Cyclin B1 in the serum of gastric cancer patients were significantly higher than those in healthy individuals (P < 0.05), while the level of Koc showed no significant difference between the two groups (P > 0.05), suggesting that Koc may not be suitable for serological diagnosis of gastric cancer. ROC analysis of the combined levels of autoantibodies against RalA, Survivin, NY-ESO-1, p53, and Cyclin B1 for gastric cancer diagnosis achieved a sensitivity of 73.68% and specificity of 78.13%, with an AUC value of 0.8767.

Conclusion: The combined tumor autoantibody detection established in this study may have promising potential applications in early screening and diagnosis of gastric cancer.