The microenvironment of mitochondria, which is the core organelle of cellular energy metabolism and apoptosis regulation, has undergone tremendous changes during cellular carcinogenesis. Mitochondrial-targeted O-CDs were synthesized by one-step hydrothermal method using polyvinyl alcohol and phenylenediamine as raw materials. The O-CDs with largest Stokes shift of 160 nm were screened out by changing the symmetry of phenylenediamine. O-CDs as a fluorescent probe presented good responsiveness and specificity to the polarity (0.23-0.32) and viscosity (1.8-950 cP). Based on the low polarity and high viscosity of tumour environment, high contrast images of different tumour/normal cell lines and tissue sections were achieved by using O-CDs as a dye, and the contrast ratios were enhanced by different multiples compared to M-CDs. The large Stokes shift and dual sensitivity of O-CDs are expected to be used to improve imaging quality and diagnostic efficiency.

The optimal number of examined lymph nodes (ELNs) for colon cancer (CC) remains controversial. This study aims to identify patient-specific factors associated with the number of ELNs retrieved in CC patients undergoing hemicolectomy and to explore the potential for establishing a minimum ELNs threshold based on patient characteristics. We retrospectively analyzed data on patients with stage I-III CC from two sources: the Chinese Multi-Institutional Registry (CMIR, N = 10,367; 2010–2018) and the Surveillance, Epidemiology, and End. Results (SEER) database (N = 121,216; 2010–2018). Logistic regression modeling was used to identify patient-specific factors associated with ELN counts. Eight distinct patient cohorts were constructed, and the relationship between ELNs and overall survival (OS) was assessed using restricted cubic spline (RCS) curves and Kaplan-Meier curves. This study was registered with the ChiCT Registry (ChiCTR2400084767). The median ELN count was 16 (IQR 12–22) in the SEER cohort and 15 (IQR 12–20) in the Chinese cohort. Age, tumor size, and location emerged as key factors influencing ELN numbers. Notably, the optimal ELN thresholds for optimal survival across all eight cohorts ranged from 14 to 17, exceeding the current recommendation of 12. Exceeding these cohort-specific thresholds was associated with significantly improved OS in both databases (all P < 0.001). The detailed comparison of ELN-related statistics between the two databases is shown in Supplementary Table X. The present study reveals heterogeneity in the minimum ELN requirements across different patient cohorts with CC. Further prospective studies and randomized controlled trials are warranted to validate these tailored thresholds and inform guideline updates.

Pleomorphic adenoma (PA) of the breast and its malignant transformation represent extremely rare clinical entities, and the molecular alterations underlying this tumor type remain largely uninvestigated to date. Herein, we report a diagnostic challenge posed by a case of mammary pleomorphic adenoma, which was initially misdiagnosed as mucinous carcinoma during frozen section examination; the definitive diagnosis was ultimately confirmed based on a comprehensive analysis of the surgical resection specimen. As implied by the term “pleomorphic,” this tumor exhibits remarkable phenotypic heterogeneity. Therefore, a thorough understanding of the morphological features of rare breast PA is crucial for mitigating the risk of misdiagnosis in clinical practice. To explore the genetic characteristics of this tumor, we employed High-throughput Chromosome Conformation Capture (Hi-C) and RNA sequencing (RNA-Seq) to detect potential gene rearrangements. Importantly, a novel PLAG1::FTO gene fusion was identified in this case. Our findings not only highlight the diagnostic complexity of this rare breast neoplasm, which is prone to misclassification, but also expand the known genetic landscape of PA through the discovery of the novel PLAG1::FTO fusion. This study thus provides valuable new insights for future molecular research on pleomorphic adenoma.

Esophageal squamous cell carcinoma (ESCC) lacks a standardized classification system, resulting in inconsistent clinical management and a suboptimal prognosis. This study addresses the urgent need for a robust consensus taxonomy to facilitate precision treatment for ESCC. We employed a network-based approach to elucidate the interconnections among eight existing classification systems, leading to the identification of four distinct consensus molecular subtypes (ECMSs): ECMS1-MET (metabolic), characterized by dysregulated metabolic pathways and NFE2L2 activation; ECMS2-CLS (classical), featuring upregulated cell cycle and canonical signaling pathways; ECMS3-IM (immunomodulatory), marked by robust immune activation and elevated PD-1 expression; and ECMS4-MES (mesenchymal), associated with mesenchymal transition, stromal activation, and VEGF signaling. To improve clinical applicability, we developed an image-based framework (imECMS) that utilizes spatial organization features (SOFs) quantified from autodelineated hematoxylin‒eosin (H&E)-stained whole-slide images through deep learning algorithms. The imECMS classifier assigns patients to one of the four ECMS subtypes, which correlate with distinct molecular characteristics, prognoses, and responses to neoadjuvant chemotherapy and immunotherapy. Validation across multiple independent cohorts confirmed that the imECMS accurately classifies ESCC subtypes from histopathological images, offering a robust and effective tool for precision medicine. In summary, the ECMS/imECMS subtyping systems we developed are the most robust frameworks for ESCC to date, providing clear biological insights and a foundation for clinical stratification and targeted therapies.

This study aims to investigate the relationship between immune cell levels, tumor markers, and metastatic colorectal cancer (mCRC), evaluate their predictive efficacy, and construct a predictive model. Retrospectively selected patients diagnosed with colorectal cancer (CRC) through pathological examination at Shanxi Cancer Hospital between January 2016 and December 2018. T-tests and chi-square tests were used to identify clinical and pathological characteristics associated with mCRC. Evaluate predictive performance using the ROC curve. A risk factor scoring system is constructed based on immune cell levels and tumor markers, categorizing patients into low-risk and high-risk groups according to their scores. Single-factor and multi-factor logistic regression analyses were employed to identify independent predictors and construct a nomogram. A total of 270 patients with CRC were included, including 45 cases of mCRC. Statistical analysis results indicate that peripheral blood laboratory indicators associated with mCRC include immune cell levels (Th, Tc, Th/Tc) and tumor markers (CEA, CA199, CA242, CA724, CA50). The risk factor scoring system revealed that the incidence of distant metastasis was significantly higher in the high-risk group than in the low-risk group (P < 0.001). Furthermore, logistic regression analysis results indicate that the risk factor score is an independent predictor of distant metastasis in CRC. A risk factor scoring system based on immune cell levels (Th, Tc, Th/Tc) and tumor markers (CEA, CA199, CA242, CA724, CA50) effectively predicts the occurrence of mCRC. This approach holds promise as a non-invasive tool for dynamic monitoring of distant metastasis risk in clinical practice.

Colorectal adenosquamous carcinoma (ASC) is an extremely rare and aggressive subtype accounting for merely 0.06% of all colorectal malignancies, with its genomic features and clinical therapeutic targets remaining largely unelucidated. This study aimed to characterize the unique genomic mutational landscape of ASC and identify clinically actionable therapeutic targets via whole-exome sequencing (WES). Tumor tissues and matched adjacent normal tissues from 3 patients with pathologically confirmed ASC were collected with ethical approval and written informed consent. Comprehensive WES and bioinformatics analyses, including strict data quality control, accurate variant detection and systematic annotation, were performed to compare the genomic profiles between ASC and conventional colorectal cancer (CRC). Key findings revealed distinct genomic characteristics of ASC that are markedly different from conventional CRC: 1.No mutations in NRAS/KRAS/BRAF, the most common driver genes in conventional CRC, were detected; instead, recurrent mutations in DNA damage repair genes (e.g., BRCA1, FANCA, WRN) and unique high-frequency mutations in MUC16 and SMYD4 were identified. 2.All ASC samples exhibited a high tumor mutational burden (TMB > 10), a clinically recognized threshold predictive of responsiveness to immune checkpoint inhibitors such as PD-1 monoclonal antibodies. 3.A panel of significantly mutated genes (SMGs) (e.g., AHNAK2, KRT40, ZNF568) and functionally enriched pathways (e.g., ABC Transporter Pathway, Adherens Junction Pathway) closely associated with tumor aggressiveness and metastasis were identified. This study concludes that ASC harbors unique genomic features that render conventional CRC therapeutic regimens ineffective. Immune checkpoint inhibitors and PARP inhibitors targeting DNA repair gene mutations represent promising first-line therapeutic options for ASC patients, while KRT40 may serve as a novel diagnostic biomarker for this rare subtype. These findings fill the critical gap in genomic research on ASC, providing a direct molecular basis for improving clinical diagnosis and formulating personalized precision therapy, though validation in larger multicenter cohort studies is warranted.

Human epidermal growth factor receptor 2 (HER2) is a key biomarker and therapeutic target in several malignancies, including breast, gastric, and other solid tumors. Recent advancements in cancer molecular profiling and the Food and Drug Administration's approval of trastuzumab deruxtecan for HER2u2010positive panu2010tumor indications have highlighted the broader relevance of HER2 alterations across diverse cancers. However, the lack of standardized guidelines for HER2 testing in a panu2010tumor context creates variability in clinical practice, hindering the optimal implementation of HER2u2010targeted therapies beyond traditional indications. To address this gap, a multidisciplinary panel of Chinese experts has developed a consensus providing comprehensive recommendations on diagnostic strategies, testing methodologies, and clinical applications of HER2 overexpression detection. By establishing a unified framework for HER2 overexpression assessment, this consensus aims to enhance the precision of HER2 testing, optimize patient selection for targeted therapies, and improve clinical outcomes across a wide spectrum of HER2 overexpression malignancies.

Human epidermal growth factor receptor 2 (HER2) is a key biomarker and therapeutic target in several malignancies, including breast, gastric, and other solid tumors. Recent advancements in cancer molecular profiling and the Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive pan-tumor indications have highlighted the broader relevance of HER2 alterations across diverse cancers. However, the lack of standardized guidelines for HER2 testing in a pan-tumor context creates variability in clinical practice, hindering the optimal implementation of HER2-targeted therapies beyond traditional indications. To address this gap, a multidisciplinary panel of Chinese experts has developed a consensus providing comprehensive recommendations on diagnostic strategies, testing methodologies, and clinical applications of HER2 overexpression detection. By establishing a unified framework for HER2 overexpression assessment, this consensus aims to enhance the precision of HER2 testing, optimize patient selection for targeted therapies, and improve clinical outcomes across a wide spectrum of HER2 overexpression malignancies.

The cellular origin and molecular mechanisms underlying therapeutic resistance in colorectal cancer remain largely unclear.This study integrates single-cell transcriptomics, spatial transcriptomics, molecular docking, and multi-cohort public databases to systematically elucidate the epithelial cell-driven drug resistance mechanism, and combines clinical pathological paraffin samples to evaluate the clinical significance and prognosis of the key protein TMEM184A. Integrated single-cell datasets underwent quality control and PCA/UMAP clustering, followed by annotation verified through spatial transcriptomic mapping. CellChat, CopyKat, inferCNV, Monocle3 and AUCell analyses were applied to assess cell–cell communication, CNV heterogeneity and pseudotime differentiation. Integrate the TCGA, GEO data, as well as the drug sensitivity data from GSCA and CTR-DB 2.0, and combine with the AutoDock molecular docking results to explore the correlation between genes and prognosis, as well as immune infiltration, and their pharmacological effects. Use the tissue microarray technique to detect the protein expression of TMEM184A in cancer tissues and adjacent tissues, and analyze its association with clinical pathological features and patient prognosis. The study identified a subset of epithelial cells associated with drug resistance, characterized by the enrichment of interferon, TNF-α/NF-κB, TGF-β, hypoxia, and p53 signaling pathways.By combining machine learning and clinical prognosis analysis, the key drug-resistant driving gene TMEM184A was finally determined. The genes related to TMEM184A were significantly enriched in the lipid metabolism pathway. Moreover, TMEM184A were highly expressed in microsatellite stable colorectal cancer, positively correlated with regulatory T cell (Treg) infiltration, and associated with the “low immune - low stroma” microenvironment. The analysis of immunohistochemical staining on tissue microarrays showed that the high expression of TMEM184A protein was related to lymph node metastasis, and was more prevalent in the rectal region. Additionally, the high expression of TMEM184A was associated with poor prognosis in patients. Drug sensitivity and molecular docking analysis indicated that TMEM184A had strong binding affinity with lapatinib and various EGFR tyrosine kinase inhibitors. TMEM184A promotes the occurrence of drug resistance in colorectal cancer by regulating lipid metabolism. The high expression of this protein in the rectum is more common and is associated with lymph node metastasis and poor prognosis in patients with colorectal cancer. This study provides a theoretical basis for TMEM184A to be used as a prognostic marker and a therapeutic target for drug resistance in colorectal cancer.

Aim:To investigate the clinicopathological features and prognostic factors of intrahepatic and extrahepatic cholangiocarcinoma. Methods:Clinicopathological and follow-up data of 328 cholangiocarcinoma patients treated at Shanxi Cancer Hospital from November 7, 2016, to August 11, 2021, were retrospectively reviewed. All samples were tested for Fibroblast growth factor receptor 2 (FGFR2) fusion by FISH. The expression of the proliferative marker Ki67 in patients with intrahepatic cholangiocarcinomas (iCCA) was evaluated by immunohistochemistry. All patients were followed up from the date of surgery to the time of death or August 31, 2023. Pathological specimens from patients with recurrence were collected and FGFR2 was tested again. Results:The positivity rates for FGFR2 fusion in intrahepatic, perihilar, and distal cholangiocarcinomas were 15%, 2.73%, and 1.69%, respectively. The chi-square test showed that tumor diameter, perineural invasion, complications, and FGFR2 fusion were statistically significant. Immunohistochemistry showed that patients with low expression of Ki67 accounted for 30% of iCCA, low expression of Ki67 and FGFR2 fusion was statistically significant. Relapse specimens were collected from 13 patients, and FISH showed that the expression of FGFR2 was consistent with that of the primary lesion. Multivariate analysis showed that lymph node metastasis was an independent factor for the prognosis of cholangiocarcinoma (P<0.05). Conclusion:CCA is an aggressive tumor with high mortality and low survival rates, especially for perihilar cholangiocarcinoma (pCCA). Therefore, it is necessary to understand the clinicopathological features and prognostic factors of iCCA, pCCA and distal cholangiocarcinoma (dCCA). In addition, lymph node status is likely to be an independent and important prognostic factor.

Although sonodynamic therapy (SDT) is a promising cancer treatment that induces DNA and macromolecular damage through the generation of reactive oxygen species (ROS), its therapeutic efficacy is limited by local hypoxia and ROS defense mechanisms in tumors. This study proposed a novel tumor treatment approach, focusing on ROS-mediated therapy by targeting the nucleus and depleting glutathione (GSH) levels, which was achieved through a nanoplatform (Pt2+-CDs@PpIX) with integrated functions including GSH detection and depletion, pH-responsive drug release, and nuclear targeting. The Pt2+-CDs@PpIX nanoplatform effectively differentiated normal and cancer cells and also exhibited excellent biocompatibility. Depletion of GSH levels and increased ROS sensitivity of cells significantly improved the effectiveness of SDT, as demonstrated in vitro using Pt2+-CDs@PpIX, which also exhibited significant cellular uptake. Pt2+-CDs@PpIX exerted potent antitumor effects in both two-dimensional and three-dimensional tumor microenvironment models (3DM-7721). Moreover, in 3DM-7721 models, hepatoma cells (SMMC-7721) demonstrated significant inhibition of motility, invasion, and colony formation after exposure to Pt2+-CDs@PpIX. Furthermore, intravenous administration of the Pt2+-CDs@PpIX nanoplatform enabled precise and rapid tumor-targeting, followed by ultrasound-triggered therapy, without adverse effects in nude mice. Hence, this nanoplatform provides a promising strategy for designing cancer therapies and delivering nuclear-targeted drugs.

This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling. We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM. Pathological evaluations were used to assess immune cell infiltration and histological features. The CRLM patients with LNM had significantly shorter CSS than patients without LNM in two large cohorts. Our results showed that nonmetastatic TDLNs exhibited a greater abundance of immune cells, including CD4+ T cells, CD8+ T cells, and CD19+ B cells, whereas metastatic TDLNs were enriched with fibroblasts, endothelial cells, and macrophages. Immunohistochemical analysis confirmed elevated levels of CD3+ T cells, CD8+ T cells, and CD19+ B cells in nonmetastatic TDLNs. The presence of nonmetastatic TDLNs was associated with enhanced antitumor immune responses in primary tumors, characterized by a higher Klintrup–Makinen (KM) grade and the presence of tertiary lymphoid structures. Furthermore, liver metastasis in patients with nonmetastatic TDLNs were predominantly of the desmoplastic growth pattern (dHGP), while those with metastatic TDLNs were predominantly of the replacement growth pattern (rHGP). This research highlights the adverse prognostic impact of LNM on patients with CRLM and reveals potential related mechanisms through multiomics analysis. Our research paves the way for further refinement of the AJCC TNM staging system for CRLM in clinical practice.

BackgroundBrentuximab vedotin (BV) has demonstrated high remission rates in clinical trials for systemic anaplastic large cell lymphoma (sALCL), yet its real-world effectiveness in China remains unconfirmed. This retrospective observational study evaluates BV-based regimens in patients with sALCL, treated from 2020 to 2023.MethodsA multi-center observational retrospective study was conducted on patients with sALCL received BV plus cyclophosphamide, doxorubicin, and prednisone (CHP) upfront or BV plus gemcitabine, oxaliplatin(GemOx), gemcitabine, cisplatin, dexamethasone(GDP), or isocyclophosphamide, carboplatin, etoposide (ICE)for later lines. Primary endpoints were complete response rate (CRR) and overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and the incidence of adverse events (AEs).ResultsAmong the 38 patients (28 newly diagnosed and 10 with refractory/relapsed disease), the ORR were 100% (with 89.3% CR) for newly diagnosed patients and 70% (with 50% CR) for refractory/relapsed patients. The median duration of response was 14 months for newly diagnosed patients and 23.8 months for those with refractory/relapsed disease. 2-year Survival rates were 100% for newly diagnosed patients and 80% for refractory/relapsed patients, with 2-year PFS rates of 92.8% and 70%, respectively. Neurological toxicities were commonly observed but resolved following the completion of treatment.ConclusionBV has proven to be effective and well-tolerated in real-world settings for the treatment of sALCL, reinforcing its potential as a promising option for first-line or subsequent therapy. The sustained efficacy observed post-CR suggests that these patients may have a prolonged disease control.

In this article, we report the first case of a 61-year-old woman who was diagnosed with both nodules and cystic lesions in her lungs. The lung nodules were diagnosed as ALK-positive histiocytosis (APH) carrying an EML4::ALK gene fusion, which microscopically displayed a mixed morphology of foamy cells, spindle cells, and Touton’s giant cells. Immunohistochemistry showed expression of CD163, CD68, and ALK, while fluorescence in situ hybridization (FISH) with second-generation sequencing (NGS) showed the ALK gene fusion with the FLCN gene variant. The patient also had bilateral multiple cystic lesions in the lungs, which were morphologically consistent with pulmonary bullae. The FLCN gene variant, in combination with the results of NGS, led to the diagnosis of Birt-Hogg-Dubé syndrome (BHD). APH and BHD are very rare, and it is easy to misdiagnose or miss the diagnosis altogether if one is not familiar with the associated histology and immunohistochemistry. It is essential for pathologists to recognize the presence of these two diseases and understand the associated histomorphologic, immunohistochemical, and cytogenetic features to enable an accurate diagnosis and differential diagnosis.

Mucosal melanoma (MM) is an uncommon and aggressive malignant tumor, characterized by a scarcity of effective treatment options and novel biomarkers. To develop novel biomarkers, a total of 89 MM tumor samples (including 50 cases in the discovery cohort and 39 cases in the validation cohort) were collected from three medical centers. Targeted bisulfite sequencing and RNA sequencing were conducted in the discovery cohort, and Cox regression analysis was employed to evaluate DNA methylation (methyDNA) and RNA expression data. Our results revealed that, compared to control samples, MM tumor samples exhibited a hypomethylated status of the Carnosine dipeptidase 1 (CNDP1) promoter (p < 0.001), which significantly up-regulated its gene expression (R = -0.815, p < 0.001) and indicated a worse prognosis (p = 0.002, hazard ratio (HR) (95% confidence interval, CI) = 0.01 (6.78E-04 ~ 0.20)). Using immunohistochemical staining, we found that CNDP1 protein was expressed in 81.8% of MM cases (36/44, including 1+/2+/3+), and high expression (2+/3+) was associated with significantly decreased overall survival (p = 0.0120, HR (95% CI) = 2.693 (1.223-5.931)). This pattern is consistent across both discovery and validation cohorts. Moreover, among the 21 patients who received immunotherapy, those with hypomethylated CNDP1 were associated with a 'cold' tumor immune microenvironment and suboptimal therapeutic outcomes (Objective Response Rate: 38% vs. 60%; Disease Control Rate: 75% vs. 100%). In conclusion, the overexpression of CNDP1, driven by promoter hypomethylation, may serve as a potential predictor of poor prognosis and diminished response to immunotherapy in MM.

Oxidative stress is a "double-edged sword" in mediating cellular activities. Here, we report that Mist1+ cells are resistant to oxidative-stress-induced cell death and that persistent oxidative stress and Kras mutation act in Knudson's "two-hit" paradigm to promote gastric cancer initiation. Reactive oxygen species (ROS) accumulation causes metaplastic lineage expansion of Mist1+ cells, licensing them as a cellular origin of gastric cancer. Mechanistically, the transcription factor Mist1 upregulates its downstream target genes Bnip3 and Tmed6, enhancing ROS resistance. Persistent ROS induce R-loop accumulation and activate YAP signaling in Mist1+ cells for proliferation and tumorigenesis. Importantly, ROS and Kras mutation synergistically drive the malignant transformation of Mist1+ cells, while ROS or Kras mutation alone could not do so. Collectively, our study offers insights into the two-hit theory by demonstrating that oxidative stress and oncogenic mutation cooperatively drive Mist1+ cell expansion and transcriptional reprogramming-critical events during early tumor initiation.

Background:Ovarian cancer is the gynecological malignancy with the highest mortality rate. Due to late detection and easy recurrence, the 5-year survival rate of advanced ovarian cancer patients is less than 30%. The current standard treatment for ovarian cancer includes platinum-based combination therapy. Most ovarian cancer patients achieve clinical remission; however, the short-term recurrence rate is still high. For patients with recurrent ovarian cancer, who are unwilling to receive chemotherapy or cannot tolerate chemotherapy after multiple lines of chemotherapy, "chemotherapy-free" treatment may be appropriate. This study aimed to investigate the preliminary mechanism of action of the antiangiogenic drug apatinib combined with poly ADP ribose polymerase (PARP) inhibitor fluzoparib as a "chemotherapy-free" regimen in the treatment of ovarian cancer patients with homologous recombination proficiency (HRP). Methods:The HRP cell line SKOV3 was used for the experiments. The cells were treated with apatinib, fluzoparib, and apatinib combined with fluzoparib, respectively. The cell proliferation rate and migration rate were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and scratch assays. Western blot was used to detect the expression of phosphorylated mitogen-activated protein kinase kinase (p-MEK), recombination activating gene 51 (RAD51), and phosphorylated histone cluster 2 H2A family member X (γH2AX). Animal experiments were performed to evaluate the effects of the combined therapy on tumor growth and drug toxicity by constructing a cell-line transplanted tumor model. Western blot was used to detect the expression of p-MEK, RAD51, and γH2AX. Immunohistochemistry (IHC) was used to detect the expression of γH2AX, phosphorylated extracellular signal-regulated kinase (p-ERK), and breast cancer 1 (BRCA1). Results:In vitro, apatinib combined with fluzoparib significantly inhibited the growth and migration of the SKOV3 cells. Western blot showed that apatinib combined with fluzoparib induced the down-regulation of p-MEK and homologous recombination (HR) pathway-related protein RAD51 expression, and increased DNA damage-related protein γH2AX expression in the SKOV3 cells. The animal experiment results showed that apatinib combined with fluzoparib had a better antitumor effect than single-drug therapy without obvious in vivo toxicity. The western blot results showed that γH2AX protein expression was increased, and p-MEK protein expression was decreased in the apatinib combined with fluzoparib group. The IHC results showed that γH2AX protein expression was increased and p-MEK protein expression was decreased in the apatinib combined with fluzoparib group. Conclusions:The combination of apatinib and fluzoparib may cause changes in the HR pathway by down-regulating MEK signaling in ovarian cancer, leading to the down-regulation of RAD51. This eventually leads to the increased expression of DNA damage-related protein γH2AX, which plays a therapeutic role in ovarian cancer in vitro and in vivo.

Lymph nodes (LNs) play a pivotal role in colorectal cancer (CRC) progression and immunity, yet their molecular and functional diversity remains poorly understood. By analyzing 630 LNs and 88 primary tumors from 200 CRC patients across four independent cohorts using bulk and single-cell RNA sequencing, we identify four non-metastatic negative LNs (NLN) subtypes (NLN_C1-C4) exhibiting obviously different immune function and stromal expansion. NLN_C3/C4 are characterized by diminished T and B cell activity and fibroblast-driven fibrosis, with follicular dendritic cell loss contributing to B cell dysfunction. Immune checkpoint inhibitors partially reverse these effects, restoring FDC and B cell activity. LNs subtypes demonstrate heterogeneity across patients and within individuals, with higher NLN_C3/C4 proportions associated with advanced tumor stages, poorer survival, and recurrence. Here, we report LNs subtypes as critical manifestations of LN heterogeneity in CRC, providing a basis for improved clinical stratification and LN-targeted therapeutic strategies.

Alpha-fetoprotein-producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer (GC). A comprehensive analysis of clinicopathological features, immunophenotypes, molecular characteristics, and survival in AFPGC contributes to identifying potential therapeutic targets and developing new strategies to manage this disease. A retrospective cohort study was conducted at Shanxi Cancer Hospital from January 2018 to December 2020, involving patients diagnosed with GC and elevated AFP serum levels. Among these, 91 patients underwent immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to reveal the immunophenotypic and molecular characteristics of AFPGC. We found that AFPGC is more common in males and primarily occurs in the cardia and antrum of the stomach. A panel of IHC markers including AFP, GPC3, SALL4, CD10, CDX-2, and ATBF1 can be used for the diagnosis and differentiating AFPGC. NGS analysis revealed that TP53 hypermutation was the most frequent molecular event associated with AFPGC. The altered signaling pathways included disease signal transduction, receptor tyrosine kinase signaling and intracellular second messenger signaling pathways. The cumulative incidence of 21 genes, based on the evidence of clinical actionability in the OncoKB, was found to be 59.34%. Among these genes, CCNE1, ERBB2, and EGFR were the most frequently observed. This underscores the potential benefit of targeted therapy for patients with AFPGC. Furthermore, LRP1B and ARID1A have been identified as prognostic factors associated with overall survival (OS) and disease-free survival (DFS), respectively. Our results aim to improve AFPGC diagnosis by identifying potential therapeutic targets and prognostic factors, which could help facilitate the development of new treatment strategies.