Objective: To investigate the clinical value of dynamic monitoring of plasma circulating tumor DNA (ctDNA) in evaluating the efficacy of immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods: Plasma samples were collected at baseline and after every 2-3 treatment cycles from 94 patients with advanced ESCC receiving second-line sintilimab monotherapy in the ORIENT-2 study. Targeted sequencing was performed to analyze somatic variants in ctDNA, and the molecular tumor burden index (mTBI) was calculated to assess dynamic changes in ctDNA. Imaging examinations were conducted synchronously with plasma sample collection, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: A total of 614 somatic mutations were detected in 93 eligible baseline plasma samples, with a median of 6 mutations per sample. Missense mutations were the most frequent mutation type. The baseline mutational profile revealed frequently mutated genes including TP53 (82%), CDKN2B (23%), and NOTCH1 (22%). In the 68 patients with both baseline and post-2-cycle plasma samples, no significant changes were observed in the variant allele frequencies (VAFs) of core driver genes before and after treatment (all P＞0.05), and no newly emerged core driver gene mutations were identified. CCND1 copy number variation was associated with shorter progression-free survival (PFS) (HR=1.88, 95% CI: 1.08-3.27), while mutations in other genes, including TP53 and NOTCH1, showed no association with PFS (all P＞0.05). None of the frequently mutated genes were associated with overall survival (OS) (all P＞0.05). Among the 68 patients, 11 (15.9%) achieved ctDNA clearance, none of whom showed tumor progression on concurrent imaging evaluation. The remaining 57 patients had ctDNA that became positive or remained persistently positive, of whom 30 (52.6%) showed tumor progression on imaging, with a statistically significant difference between groups (P=0.002). Compared with patients whose ctDNA became or remained positive, those with ctDNA clearance exhibited significantly delayed tumor progression (HR=2.05, 95% CI: 1.06-3.96), but ctDNA status after 2 cycles did not significantly affect OS (HR=1.38, 95% CI: 0.62-3.09). After 2 cycles of treatment, patients in the low mTBI group had a higher disease control rate (DCR) than those in the high mTBI group [73.5% (25/34) vs. 38.2% (13/34), P=0.007], as well as superior PFS (HR=2.80, 95% CI: 1.65-4.75) and OS (HR=3.54, 95% CI: 1.95-6.42). Dynamic changes in mTBI were highly consistent with concurrent imaging response assessments. The molecular response group had a significantly higher DCR than the non-response group [87.5% (21/24) vs. 42.2% (19/45), P＜0.001], as well as superior PFS (HR=2.39, 95% CI: 1.41-4.06) and OS (HR=2.77, 95% CI: 1.46-5.22). Among 32 patients with stable disease (SD) at the first imaging evaluation after 2 cycles, those in the molecular response group had comparable PFS with the non-response group (HR=1.03, 95% CI: 0.51-2.08, P=0.942), but significantly longer OS (HR=3.12, 95% CI: 1.20-8.06). Conclusion: Dynamic monitoring of the ctDNA-based molecular tumor burden index (mTBI) provides real-time and sensitive molecular information for evaluating the efficacy of immunotherapy in advanced ESCC, demonstrating definite clinical value for personalized treatment management.

Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic significance, and assess its involvement in immune regulation. Methods: The expression, prognostic value, and correlation with tumor immunogenicity of CENPN in BRCA tissues were analyzed based on The Cancer Genome Atlas (TCGA) database. Verification was conducted using cancerous and adjacent normal tissues from BRCA patients who underwent surgical treatment at Yantai Mountain Hospital between January 2022 and April 2023. CENPN expression in various immune cells in the blood was examined using the Human Protein Atlas (HPA) database. Genetic alterations of CENPN in breast cancer tissues were analyzed via the cBioPortal database. CENPN-related genes were screened using the GEPIA 2.0 database, and the interaction network between CENPN and similar genes was visualized with the STRING database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the potential biological functions of CENPN. The correlation between CENPN expression and immune cell infiltration, as well as immune cell markers in BRCA tissues, was assessed using the TIMER 2.0 database. The effect of CENPN on the proliferation ability of breast cancer MCF-7 cells was detected by the CCK-8 assay, and its impact on the migration ability of MCF-7 cells was evaluated by a wound healing assay. Results: Analysis of TCGA database data revealed that CENPN expression was significantly higher in BRCA tissues compared to adjacent normal tissues (P＜0.05). Validation in our institutional cohort demonstrated a significantly higher positivity rate for CENPN in the 17 breast cancer tissues (82.4%) than in the paired paracancerous tissues (5.9%, P＜0.001). According to the HPA database, elevated CENPN expression was observed in T-reg cells, naïve B cells, and myeloid dendritic cells. Kaplan-Meier survival analysis indicated that patients with high CENPN expression had poorer overall survival (HR=1.39, P＜0.001), recurrence-free survival (HR=1.31, P＜0.001), post-progression survival (HR=1.28, P=0.036), and distant metastasis-free survival (HR=1.6, P＜0.001). Correlation analysis revealed a negative association between CENPN expression and tumor mutational burden in BRCA patients (r=-0.196, P＜0.001). Furthermore, CENPN expression was positively correlated with 5 out of 20 common immune checkpoint genes and negatively correlated with the remaining 15, suggesting its potential for predicting immunotherapy response. Analysis via the cBioPortal database showed that invasive lobular breast carcinoma had the highest CENPN alteration frequency, with amplification being the most common alteration in BRCA. Invasive mixed mucinous breast carcinoma exhibited the highest mutation frequency, and a key missense mutation (K329N) was identified as a potential driver in BRCA.GO enrichment analysis demonstrated that CENPN-related genes were primarily involved in cell cycle, DNA metabolic processes, cell division, nuclear lumen, chromosomes, nucleoplasm, and functions related to ATP, nucleotide, and small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in BRCA. Positive correlations were also found with markers for CD8+ T cells, B cells, T cells, and T-cell exhaustion.CCK-8 assay and wound healing experiments confirmed that CENPN knockdown significantly suppressed malignant phenotypes, including proliferation and migration, in MCF-7 cells. Additionally, CENPN knockdown was found to enhance the chemosensitivity of MCF-7 cells to the anti-tumor agents 5-fluorouracil and gemcitabine. Conclusion: CENPN serves as a potential prognostic biomarker and a novel target for immunotherapy in BRCA.

Objective: This study aims to investigate the expression characteristics of GLUT10 in breast cancer and its role in mediating cisplatin resistance, with the goal of providing a new molecular target for personalized breast cancer treatment. Methods: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were analyzed using the GEPIA2 platform to assess pan-cancer expression, while the UALCAN platform was used to analyze expression differences between breast cancer and normal breast tissues. In vitro, SK-BR-3 cells were divided into three groups: shScr (transfected with non-targeting scrambled shRNA), shSLC2A10#1, and shSLC2A10#2. MDA-MB-231 cells were divided into a vector control group and an SLC2A10 overexpression group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect SLC2A10 mRNA expression. Western blotting was used to detect GLUT10 and cleaved caspase-3 protein expression. The CM-H2DCFDA probe was used to measure intracellular reactive oxygen species (ROS) levels. Drug sensitivity and colony formation assays were performed to evaluate cisplatin sensitivity, and flow cytometry was used to detect apoptosis rates. Results: GEPIA2 analysis showed that GLUT10 expression was downregulated in adrenocortical carcinoma, cervical squamous cell carcinoma and adenocarcinoma, and kidney chromophobe tumor tissues compared to normal tissues, whereas it was upregulated in invasive breast cancer, glioma, skin melanoma, and thymoma. UALCAN analysis revealed that SLC2A10 mRNA levels in breast cancer tissues were 1.85-fold higher than in normal breast tissues (P＜0.001). RT-qPCR results showed that SLC2A10 mRNA expression levels in breast cancer cell lines, ranked from high to low, were Hs 578T (160.5±12.3), SK-BR-3 (115.2±10.5), MDA-MB-468 (50.1±5.2), T-47D (35.4±4.1), and MCF7 (25.6±3.8), all significantly higher than in normal breast epithelial cells (P＜0.001). In SK-BR-3 cells, compared with the shScr group, the shSLC2A10#1 and shSLC2A10#2 groups exhibited increased intracellular ROS levels (relative fluorescence intensity: 1.78±0.12 and 2.05±0.15, respectively; P＜0.05), increased cisplatin sensitivity, reduced colony numbers, and promoted cisplatin-induced ROS accumulation and apoptosis. In MDA-MB-231 cells, compared with the vector control group, the SLC2A10 overexpression group showed decreased intracellular ROS levels (relative fluorescence intensity: 0.58±0.09, P＜0.05), decreased cisplatin sensitivity, and inhibited cisplatin-induced ROS accumulation and apoptosis. Conclusion: GLUT10 is highly expressed in breast cancer and mediates cisplatin resistance by regulating ROS levels, suggesting it may serve as a novel therapeutic target for reversing drug resistance in breast cancer.

This study aims to integrate network pharmacology, machine learning, and survival analysis to preliminarily explore the molecular mechanisms underlying the inhibitory effects of thalidomide on the malignant transformation of oral leukoplakia (OLK).

To investigate the effects of miR-183-5p overexpression on proliferation, invasion, migration, and ferroptosis of triple-negative breast cancer (TNBC) cells and the role of Kelch-like protein 24 (KLHL24) in mediating these effects.

Colorectal cancer is a common gastrointestinal malignancy worldwide. KRAS gene mutation is an important molecular feature of colorectal cancer, but the clinical significance of different mutation sites remains unclear. This study aims to investigate the distribution characteristics of specific KRAS gene mutation sites and analyze their associations with clinicopathological parameters and survival outcomes in patients with colorectal cancer, thereby providing a basis for precise stratified diagnosis and treatment.

We reported a rare case in which acute pulmonary thromboembolism (APTE) was the initial clinical manifestation of multiple endocrine neoplasia type 1 (MEN1). A 44-year-old male presented with chest tightness and dyspnea, and was subsequently diagnosed with acute pulmonary embolism on computed tomography pulmonary angiography (CTPA). Medical history revealed a long-standing pituitary adenoma. During the etiologic evaluation, the patient was found to have a hypercalcemic crisis, hyperparathyroidism, and a pancreatic neuroendocrine tumor. Genetic testing confirmed a pathogenic MEN1 mutation (c.1664G>A), which established the diagnosis of MEN1. Along with regular anticoagulation therapy, the patient underwent multidisciplinary evaluation. Oral bromocriptine was continued for the pituitary adenoma, and parathyroidectomy was performed after correction of the hypercalcemic crisis. The pancreatic neuroendocrine tumor is being closely monitored, with elective surgery or somatostatin analogue therapy planned as appropriate to eliminate the underlying cause of pulmonary embolism. Through a brief literature review, we explored how MEN1 may contribute to a hypercoagulable state. The case highlighted the importance of endocrine and genetic screening in patients with unexplained pulmonary embolism.

Objective: To investigate the clinicopathological and molecular features of atypical spindle cell/pleomorphic lipomatous tumor (ASPLT). Methods: A retrospective analysis was conducted on nine cases of ASPLT diagnosed at the Fourth Affiliated Hospital of Soochow University and the First Hospital of Jilin University from February 2023 to September 2025. The clinical, histopathologic, immunohistochemical, and molecular genetic features were analyzed, supplemented by a comprehensive literature review. Results: The cohort comprised seven males and two females with an age of 59.0 (54.0, 63.0) years. Tumor arose in the neck, buttock, abdominal wall, face, and axilla. Histologically, the tumors exhibited a variable mixture of atypical spindle cells, adipocytes, pleomorphic/multinucleated cells, and lipoblasts embedded within a collagenous-to-myxoid stroma. Distinctive ropy collagen bundles were identified in seven cases. Mitotic activity was negligible, and tumor necrosis or dedifferentiation was consistently absent. Immunohistochemically, all cases showed diffuse CD34 expression and loss of nuclear RB1 expression. The Ki-67 proliferative index was 1%-2%, and p53 immunostaining demonstrated a wild-type expression pattern in all eight tested cases. Fluorescence in situ hybridization confirmed RB1 gene deletion in all five tested cases. Conclusions: ASPLT is a rare adipocytic neoplasm characterized by a broad morphologic spectrum, distinctive genetic alterations, and an indolent clinical course. Due to substantial morphological overlap with other lipomatous tumors, diagnosis can be challenging. Accurate identification relies on meticulous microscopic evaluation combined with ancillary testing, specifically, CD34 positivity, immunohistochemical loss of RB1 expression, and/or molecular detection of RB1 gene deletion, to ensure correct classification and prevent overtreatment.

Objective: To investigate the molecular mechanisms by which secretory carrier membrane protein 2 (SCAMP2) contributes to colorectal cancer cell proliferation via regulating early growth response factor 1 (EGR1). Methods: Ten pairs of pathologically confirmed colorectal cancer tissues and adjacent non-tumor tissues were collected at the Affiliated Hospital of Qingdao University between January 2022 and March 2023. The expression of SCAMP2 was examined using Western blot and immunohistochemistry. SW480 and HT29 cell lines were transfected with small interfering RNA (siRNA), short hairpin RNA (shRNA) and SCAMP2/EGR1 overexpression plasmids to establish cell models with SCAMP2 or EGR1 overexpression and knockdown. Cell counting kit-8 (CCK8) assay, flow cytometry and nude mouse subcutaneous tumorigenesis assay were performed to evaluate the effects of SCAMP2 expression on the proliferation and apoptosis of colorectal cancer cells. Transcriptome sequencing was performed to identify early growth response factor 1 (EGR1) as the downstream regulatory factor of SCAMP2. Rescue experiments were used to confirm the interaction between SCAMP2 and EGR. Results: Western blot demonstrated that the expression level of SCAMP2 in 7 pairs of colorectal cancer tissues was lower than that in adjacent normal intestinal tissues. Immunohistochemistry revealed that SCAMP2 showed strongly positive staining (3+) in normal intestinal epithelium, but negative/weakly positive staining (1+) in colorectal cancer. Consistently, EGR1 exhibited strongly positive immunoreactivity (3+) in normal intestinal epithelium, but negative/weak positive staining (1+) in colorectal cancer. In vitro cellular experiments confirmed that overexpression of SCAMP2 or EGR1 significantly suppressed the proliferation of colorectal cancer cells (all P<0.05). Furthermore, the nude mouse xenograft tumor model showed that SCAMP2 overexpression remarkably inhibited tumor growth in vivo (P<0.05). Transcriptome sequencing showed that the mRNA expression level of EGR1 was significantly up-regulated in SCAMP2-overexpressing colorectal cancer cells (P<0.05). Rescue experiments illustrated that knockdown of EGR1 partially reversed the inhibitory effects on cell proliferation and pro-apoptotic effects induced by SCAMP2 overexpression. Conversely, overexpression of EGR1 partially abrogated the enhanced proliferation and reduced apoptosis triggered by SCAMP2 knockdown. Conclusions: SCAMP2 expression is downregulated in colorectal cancer. Low SCAMP2 expression may impair EGR1 signaling, thereby suppressing apoptosis and promoting colorectal cancer cell proliferation. The SCAMP2/EGR1 signaling axis plays a crucial role in colorectal cancer progression.

Objective: To investigate the associations of aberrant CD10 expression with clinicopathological features and prognosis of marginal zone lymphoma (MZL). Methods: A retrospective analysis was conducted on 13 cases of MZL with aberrant CD10 expression, diagnosed at the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China between April 2015 and July 2024. Clinical features, morphological findings, immunohistochemical profiles, and molecular testing results were analyzed. The patients were also assessed via telephone follow-up. Results: There were 7 male and 6 female patients, aged 55.0 (51.5,70.0) years on average. Subtypes comprised 10 extranodal MZLs of mucosa-associated lymphoid tissue (EMZL), 2 splenic MZLs (SMZL), and 1 nodal MZL (NMZL). Histologically, tumor cells exhibited diffuse (10 cases) or nodular (3 cases) growth patterns. In all three nodular cases, the proportion of CD10-positive cells was 50% or higher. Under high-power magnification, most cases (12 of 13 cases) were dominated by proliferation of small lymphocyte-like cells. One case was characterized by a mixed proliferation of monocytoid B cells and small lymphocyte-like cells. Histological features included follicular colonization (8 cases) and lymphoepithelial lesions (2 gastric cases and 2 pulmonary cases). Plasma cell differentiation was observed in 10 cases (9 EMZLs and 1 NMZL) and scattered interstitial hemosiderin deposits were seen in 7 cases (5 EMZLs and 2 SMZLs). Immunophenotypically, tumor cells expressed CD20 (13/13 cases), CD79α (11/13 cases), and bcl-2 (12/13 cases), whereas CD3, bcl-6, and Cyclin D1 were all negative. All 13 cases were positive for CD10, with the proportion of positive cells ranging from 5% to 80%. Among them, 6 cases exhibited CD10 positivity in less than 50% of tumor cells, and 7 cases showed CD10 positivity in 50% or more of tumor cells. The Ki-67 proliferation index ranged from approximately 5% to 30%. Molecular testing revealed monoclonal immunoglobulin gene rearrangement in 2 cases, MALT-1 gene break in one EMZL case, and no bcl-2 gene break in 10 MZL cases. Follow-up durations ranged from 11 to 122 months. Favorable post-treatment outcomes were observed in all 13 patients. Conclusions: MZL with aberrant CD10 expression is a rare variant, demonstrating clinicopathological features similar to conventional MZL and a generally favorable prognosis. Its immunophenotype may mimic other CD10-positive small B-cell lymphomas, particularly follicular lymphoma. An accurate diagnosis appears to require integration of histologic, immunophenotypic, and molecular findings to avoid misdiagnosis.

Objective: To investigate the clinicopathological features, immunophenotype, and molecular characteristics of sweat gland carcinoma with neuroendocrine differentiation (SCAND). Methods: Three cases of SCAND diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from June 2022 to June 2025 were collected. Hematoxylin-eosin (HE) staining and immunohistochemistry (EnVision method) were performed to characterize morphologic and immunophenotypic features. Next-generation sequencing (NGS) was utilized to explore their molecular pathological characteristics. Results: All three patients were male, aged 67, 63, and 48 years, respectively. The primary tumors presented as solitary nodules or masses located in the lower abdomen, anterior chest wall, or inguinal region, with a maximum diameter of 2.0, 1.3, and 1.8 cm, respectively. Histologically, the tumors were situated primarily within the dermis, invading the epidermis and subcutaneous tissue, with focal mucin production. The tumor cells were arranged in nests, cords, and sieve-like patterns, exhibiting mild to moderate atypia. The nuclei were round to oval with coarsely granular chromatin and relatively inconspicuous nucleoli, accompanied by eosinophilic cytoplasm. Mitotic figures were scarce. All cases were positive for CK7, GATA3, TRPS1, Ber-EP4, epithelial membrane antigen, estrogen receptor, progesterone receptor, and the neuroendocrine markers of synaptophysin and chromogranin A. The tumors were negative for p40 and HER2. The Ki-67 proliferation index ranged from 2% to 30%. Multiple class Ⅲ and Ⅳ variants were identified by NGS analysis in cases 1 and 2. In case 3, a class Ⅱ variant, specifically an SF3B1 missense mutation, was identified along with multiple class Ⅲ and Ⅳ variants. Additionally, multiple germline variants were detected in all three cases, while none of them were classified as pathogenic or likely pathogenic. The patients were followed up for 13, 37 and 155 months, respectively. Metastases were detected 6, 36, and 96 months after diagnosis. Case 2 showed local metastasis, while cases 1 and 3 developed multiple nodal and bone metastases. Conclusions: SCAND is a rare cutaneous adnexal neoplasm characterized by co-expression of sweat gland and neuroendocrine markers. Despite low-grade morphology, it follows a non-indolent clinical course warranting close clinical attention.

To explore the correlation between CD269 expression patterns in multiple myeloma (MM) cells and the expression of other antigens and molecular cytogenetics.

To investigate the relationship between TP53 and MYD88 mutations and treatment efficacy in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based standard chemoimmunotherapy.

To investigate the gene mutations in tumor tissues of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL), and analyze its relationship with clinical features and prognosis.