Objective: To investigate FGFR1 mRNA expression and gene characteristics in breast cancer tissue. Methods: Breast cancer samples from 45 female patients (10 HER2-positive, 15 triple-negative and 20 HR-positive/HER2-negative cases) were collected from Peking Union Medical College Hospital between December 2022 and January 2024. FGFR1 mRNA expression was identified using reverse transcription droplet digital PCR, and the FGFR1 gene characteristics was analyzed from 30 samples by fluorescence in situ hybridization. Results: In the group of HER2-positive, 2 cases (2/10) of high FGFR1 mRNA expression and one case (1/7) of high FGFR1 gene amplification were found. Five tumors (5/15) with high FGFR1 mRNA expression, one (1/10) with gene amplification and one (1/10) with low-level amplification of FGFR gene were identified in triple-negative breast cancer. Among HR-positive/HER2-negative samples, high FGFR1 mRNA expressions were confirmed in 4 cases (4/20), with no FGFR1 gene amplification (0/13). Additionally, 3 cases (3/10) showed high FGFR1 mRNA expression in HER2-low expression (IHC 1+and IHC 2+/FISH-) samples. Conclusions: High FGFR1 mRNA expression is observed across different molecular subtypes of breast cancer. High-level FGFR1 gene amplification is uncommonly detected; therefore, further studies with large amount samples are required.

Molecular subtyping and detection of other molecular characteristics of endometrial cancer have been widely carried out and applied in clinical diagnosis and treatment. However, there are still many issues, including inconsistent molecular testing methods and the lack of high-quality evidence to guide standardized clinical diagnosis and treatment based on molecular characteristics. For molecular subtyping detection, it is recommended to conduct a comprehensive molecular subtyping assessment by combining immunohistochemistry (IHC) and next-generation sequencing (NGS). Clinically, the molecular subtyping of endometrial cancer, traditional pathological classification, and surgical pathological staging should be considered holistically, and individualized treatment plans should be formulated based on the latest available clinical evidence. POLE-mutant (POLEmut) endometrial cancer generally has a favorable prognosis, and immune checkpoint inhibitors (ICIs) may be an effective adjuvant treatment option for advanced POLEmut endometrial cancer. For stage Ⅲ and above mismatch repair-deficient (MMRd) endometrial cancer, postoperative paclitaxel plus carboplatin chemotherapy combined with ICIs and maintenance therapy are recommended. No specific molecular profile (NSMP) endometrial cancer should undergo risk stratification based on estrogen receptor (ER) expression level and pathological type, and high-risk NSMP should be treated with reference to p53-abnormal (p53abn) endometrial cancer. Precision diagnosis and treatment of endometrial cancer based on molecular characteristics are still in the stage of in-depth exploration and verification. Many issues remain to be resolved, such as whether MMRd endometrial cancer caused by MLH-1 methylation or mutations in MMR-encoding genes has consistent responses to ICIs, and how to predict treatment efficacy. The reduced cost and rapid popularization of high-throughput technologies, as well as the continuous expansion and improvement of evidence from prospective cohorts, will provide high-quality evidence for further refinement of molecular characteristics and risk stratification of endometrial cancer, and guide the implementation of precision treatment for this disease.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare and highly aggressive mesenchymal neoplasm that is frequently associated with anaplastic lymphoma kinase (ALK) gene fusion. Surgical resection remains the cornerstone of treatment for patients with early- and intermediate-stage EIMS; however, a standardized therapeutic approach for advanced-stage EIMS has yet to be established. Primary pulmonary EIMS is exceedingly rare, with only a limited number of cases reported in the literature. While treatment with ALK-tyrosine kinase inhibitors (TKIs) is considered a viable therapeutic option, and clinical outcomes with monotherapy using ALK-TKIs have frequently been suboptimal. This study presents a case of advanced primary pulmonary EIMS with a TPM3-ALK fusion. The patient received first-line targeted therapy with the second-generation ALK-TKI Ensartinib, in conjunction with radiotherapy for residual and metastatic lesions. This treatment regimen resulted in significant tumor reduction and sustained disease control. The progression-free survival (PFS) exceeded 32 months, with no significant treatment-related adverse events observed. This study investigates the feasibility of combining targeted therapy with local radiotherapy, guided by genetic testing, to offer novel treatment strategies for patients with advanced primary pulmonary EIMS.
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Cancer treatment is a significant challenge facing global medicine, with complex molecular mechanisms and drug resistance being key factors limiting treatment outcomes. Abnormal lipid metabolism is one of the important characteristics of tumors, providing metabolic support for the growth, proliferation, migration, and invasion of tumor cells. Tumor suppressor p53 protein and sterol O-acyltransferase 1 (SOAT1) play an important role in regulating cellular lipid metabolism and are closely related to the occurrence, development, and prognosis of various tumors. p53 protein regulates tumor lipid metabolism through multiple signaling pathways, while SOAT1, as a key enzyme in cholesterol esterification, is highly expressed in many tumors and accelerates tumor progression. Recent studies have shown that there may be a functional association between p53 protein and SOAT1, coordinating the regulation of lipid homeostasis in tumor cells. This article reviews the research progress on p53 protein and SOAT1 in tumor lipid metabolism, focusing on the potential mechanisms of action of the p53-SOAT1 axis in tumor development, and prospects its application prospects as a target for cancer treatment.
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Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), and epidermal growth factor receptor (EGFR) mutation is its primary molecular driver event. Although the third-generation tyrosine kinase inhibitors (TKIs) Osimertinib has become the standard first-line therapy for such patients, the development of drug resistance severely limits long-term survival benefits. However, increasing evidence suggests that epigenetic remodeling is a crucial non-genetic mechanism contributing to resistance. Specifically, hypermethylation of DNA promoter regions can assist tumor cells in evading drug cytotoxicity by silencing key tumor suppressor genes or metabolic regulatory genes. This study aims to identify key genes regulating Osimertinib sensitivity through machine learning and high-throughput screening, and to dissect the role of methylation modifications in regulating primary resistance to Osimertinib.

Leptomeningeal metastasis (LM) is a devastating complication of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), with a poor prognosis. While high-dose third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can enhance drug concentrations in the central nervous system, their efficacy as monotherapy remains limited. Intrathecal Pemetrexed (IP) offers a promising local treatment approach by bypassing the blood-brain barrier and acting directly within the cerebrospinal fluid. However, clinical data on the efficacy and safety of combining high-dose third-generation EGFR-TKIs Furmonertinib (160 mg/d) with IP in EGFR-mutant NSCLC-LM patients are still scarce. Therefore, this study aims to evaluate the efficacy and safety of this combination regimen in this population to provide real-world data support for clinical practice.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a newly defined type of epithelial tumor in the 2021 World Health Organization (WHO) fifth edition classification of thoracic tumors, with a low incidence. Currently, its treatment and prognosis remain unclear. Pathologically, it can be distinguished from SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) based on histological morphology and immunohistochemistry, yet whether there are differences in their clinical features, sensitivity to radiotherapy, and prognosis remains unknown. This study aimed to analyze the clinical characteristics of patients with SMARCA4-UT and SMARCA4-dNSCLC and to identify prognostic factors.

To evaluate the associations of serum methotrexate (MTX) concentrations and MTHFR gene polymorphisms with delayed metabolism of high-dose MTX and adverse reactions in children with acute lymphoblastic leukemia (ALL).

Objective: To investigate the effects of visceral fat and subcutaneous fat distribution and the expression level of serum Takeda G protein-coupled receptor 5 (TGR5) on the clinicopathologic features and postoperative recurrence and metastasis of patients with endometrial cancer (EC). Methods: This was a retrospective cohort study. A total of 146 EC patients who underwent laparoscopic radical resection of EC at Northwest Women and Children's Hospital from March 2020 to March 2024 were enrolled as the EC group, and 153 concurrent patients with benign endometrial lesions were enrolled as the control group. The EC group was followed up for 1 year after the surgery to analyze the prognosis. Depending on whether recurrence and metastasis occurred, the EC group was further divided into the recurrence or metastasis subgroup (n=45) and the non-recurrence or metastasis subgroup (n=101). Age, obstetric history, body mass index (BMI), serum TGR5 level, visceral fat area (VFA) and subcutaneous fat area (SFA) were collected and compared between the recurrence or metastasis subgroup, non-recurrence or metastasis subgroup and the control group. The area under curve, sensitivity, specificity and the Youden index of the predictive value of TGR5 expression level, VFA level, SFA level, and BMI in patients in the EC group were analyzed using receiver operating characteristic (ROC) curves. Based on the cut-off value determined by the Youden index, the patients in the EC group were further classified into high-expression/high-level and low-expression/low-level groups. Univariate and multivariate Cox proportional hazards regression models were used to identify the risk factors for recurrence and metastasis of patients in the EC group in 1 year. The one-year recurrence and metastasis of EC patients with different serum TGR5 expression levels, VFA levels, SFA levels and BMI were analyzed, survival curves were plotted and data of recurrence-free survival (RFS) were obtained using the Kaplan-Meier method. ROC curves were constructed to evaluate the diagnostic efficacy of serum TGR5 expression level, VFA level, SFA level, BMI and their combined indicators. Results: The serum TGR5 expression level, VFA level, SFA level and BMI were significantly higher in the recurrence or metastasis subgroup compared to the non-recurrence or metastasis subgroup (all P<0.05). Furthermore, all four indicators in both the recurrence or metastasis subgroup and the non-recurrence or metastasis subgroup were significantly higher than those in the control group (all P<0.05). When the serum TGR5 expression level was 7.7 μg/L, the VFA level was 90.4 cm², the SFA level was 221.6 cm², and the BMI was 23.9 kg/m², the Youden index reached its maximum value for each respective parameter. Cox regression analyses revealed that serum TGR5≥7.7 μg/L (HR=6.382, 95%CI:2.151-18.939, P=0.001), VFA≥90.4 cm² (HR=6.914, 95%CI:2.279-20.979, P=0.001), SFA≥221.6 cm² (HR=7.520, 95%CI:2.414-23.421, P=0.001) and BMI≥23.9 kg/m² (HR=9.434, 95%CI:3.019-29.473, P<0.001) were risk factors for recurrence and metastasis within 1 year after surgery. The incidence of postoperative recurrence and metastasis in the high TGR5 expression group, high VFA level group and high SFA level group were significantly higher, while the RFS times were significantly shorter than those in the low TGR5 expression group, low VFA level group and low SFA level group (all P<0.05). ROC curve analysis showed that the above independent factors had good evaluation efficacy, and the combined detection was superior to single indicator detection. Conclusions: EC patients with high serum TGR5 expression level, VFA level and SFA level have a higher recurrence and metastasis rate. High serum TGR5 expression level, high VFA level, high SFA level and high BMI are risk factors for recurrence and metastasis within 1 year after radical resection of EC, and the diagnostic value of combined detection is superior to single indicator detection.

Objective: To investigate the mutation status of breast cancer susceptibility genes (BRCA) in colorectal cancer and the relationship between BRCA and the clinical-pathological characteristics and prognosis of colorectal cancer. Methods: A total of 132 colorectal cancer tissue specimens surgically resected at Shanxi Cancer Hospital from 2018 to 2021 were collected. Second-generation sequencing was used to detect BRCA mutations. Immunohistochemical staining assessed the infiltration density of CD3+, CD4+, and CD8+ T cells, and CD20+ B cells. The association between BRCA mutations and clinical-pathological features, immune cell infiltration density, and prognosis of colorectal cancer was analyzed. Results: Among 132 colorectal cancer cases, the overall BRCA mutation rate was 9.09% (12/132), with BRCA1 mutation rate at 3.03% (4/132) and BRCA2 mutation rate at 6.06% (8/132). Compared with the BRCA wild-type group, the BRCA mutation group exhibited smaller tumors (P=0.036), less vascular or nerve invasion (P=0.041), and lower tumor budding grades (P=0.013). Tumor microenvironment analysis revealed that the infiltration densities of CD3+, CD4+, and CD8+ T cells in the BRCA mutation group were 1 729.66 (652.91, 3 065.98)/mm², 438.36 (97.37, 718.43)/mm², and 1 017.86 (506.19, 2 257.35)/mm², respectively, all higher than those in the BRCA wild-type group [555.72 (304.58, 933.26)/mm², 89.34 (58.15, 178.35)/mm², and 354.23 (157.78, 752.37)/mm², respectively, all P＜0.05]. Molecular feature analysis revealed five cases of TMB-H in the BRCA-mutant group and three cases in the BRCA-wild group, with a statistically significant difference between the two groups (P＜0.001). Survival analysis revealed no association between BRCA mutation status and overall survival in colorectal cancer patients (P＞0.05). Multivariate Cox regression analysis identified clinical stage as an independent predictor of overall survival, with patients at stages Ⅲ-Ⅳ exhibiting poorer prognosis (HR=5.359, 95% CI: 1.124-25.546). Conclusion: BRCA-mutated colorectal tumors exhibit lower invasiveness, higher TMB-H rates, and abundant immune cell infiltration in the tumor microenvironment, suggesting that patients with BRCA-mutated colorectal cancer are more likely to benefit from immunotherapy.

To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene.

We retrospectively analyzed the clinical data and clonal architecture of two multiple myeloma (MM) patients harboring concurrent IGH::FGFR3 and IGH::CCND1 fusions, with a review of relevant literature. Fluorescence in situ hybridization (FISH) confirmed biallelic IGH translocations in both cases. Case 1, diagnosed with smoldering MM (SMM), exhibited co-positivity for both IGH translocations in 91% of bone marrow plasma cells. Case 2, with active MM, showed predominant IGH::FGFR3 positivity (93% of cells), with a minor subclone (5%) co-expressing IGH::CCND1. This study demonstrates that primary biallelic IGH translocations can lead to the coexistence of IGH::FGFR3 and IGH::CCND1, revealing a novel genetic mechanism driven by biallelic IGH translocations in the founding clone. Furthermore, it elucidates the clonal heterogeneity in biallelic IGH translocation events.

We retrospectively analyzed the RUNX1 mutation status and clinical characteristics of 323 newly diagnosed acute myeloid leukemia (AML) patients treated in the Second Affiliated Hospital of Anhui Medical University from February 2018 to May 2023. The mutation rate of RUNX1 in AML patients was 11.5% with a median mutation frequency of 40.4%. RUNX1 mutations often coexisted with other mutations, such as ASXL1, but were mutually exclusive with NPM1 mutations. AML patients with RUNX1 mutations were older (median age: 65 vs 55 years, P<0.01), had a lower complete remission rate (39.4% vs 79.8% P<0.01), higher relapse (75.0% vs 48.8%, P<0.05) and mortality (91.4% vs 59.5%, P<0.01) rates, shorter median overall survival (OS) (5.9 vs 20.1 months, P<0.01) and relapse-free survival (RFS) (9.5 vs 46.5 months, P<0.01). A high RUNX1 mutation frequency was associated with increased mortality (100.0% vs 76.5%, P<0.05) and shorter RFS (7.2 vs 12.2 months, P<0.05). Different induction therapies (chemotherapy/low-intensity treatment) showed no significant impact on the efficacy or prognosis of patients with RUNX1 mutations (P>0.05). Patients with concurrent RUNX1 and DNMT3A or ASXL1 mutations portend a poorer prognosis, and the cooccurrence of FLT3-ITD mutation further leads to inferior therapeutic outcomes.

Objective: To explore the characteristics and auxiliary diagnostic value of T-cell receptor (TCR) gene rearrangement in T-cell abnormal clonal diseases, including T-cell large granular lymphocytic leukemia (T-LGLL) . Methods: Altogether, 103 newly diagnosed patients with T-LGLL, 18 with aplastic anemia (AA), 3 with pure red cell aplasia, 111 with systemic lupus erythematosus (SLE), and 30 healthy controls admitted at Jiangsu Province Hospital from September 2011 to November 2023 were enrolled. TCR gene rearrangement was detected by polymerase chain reaction and capillary electrophoresis, and TCRβ chain variable region (TCRVβ) subfamily and TCRβ chain constant region 1 (TRBC1) were detected by flow cytometry. The auxiliary diagnostic value of these three detection methods for T-LGLL was compared. Meanwhile, Sanger sequencing was used to detect STAT3 gene mutations in T-LGLL patients, and the mutation characteristics and clinical features of these patients were analyzed. Results: In T-LGLL patients, 57 were men and 46 were women, and the patients' median age was 61 (28-81) years. Altogether, 97.1% (100/103) of the patients were positive for TCR gene rearrangement, and TCRβ gene rearrangement showed the highest incidence (95.1%, 98/103). TCRβ gene rearrangements were further classified into TCRβ (V-J) (42.9%, 42/98), TCRβ (D-J) (15.3%, 15/98), and copositive for two TCRβ gene rearrangements (41.8%, 41/98). This was followed by TCRγ (47.6%, 49/103) and TCRδ (4.9%, 5/103) gene rearrangements. The detection rates of TCRVβ and TRBC1 were 89.5% (51/57) and 73.5% (25/34), respectively. The detection rate of TRBC1 was significantly lower than that of TCR gene rearrangement (P=0.004). The detection rates of TCR gene rearrangement in the AA, SLE, and healthy control groups were 19.0%, 6.3%, and 3.3%, respectively. Compared with healthy controls and SLE patients, the T-LGLL patients had significantly lower HGB, RBC, and ANC but significantly higher absolute lymphocyte count (ALC) (all P<0.01). Compared with the AA group, the white blood cell count, ALC, and platelet counts of the T-LGLL patients were significantly higher (all P<0.001). Compared with the AA, SLE, and healthy control groups, the T-LGLL patients were older and had a significantly higher detection rate of TCR gene rearrangement (all P<0.05). Within the T-LGLL cohort, patients with positive TCRβ (D-J) gene rearrangement had significantly lower incidence of autoimmune diseases (3.6% vs 19.1%, P=0.011) and HGB of ≥100 g/L (33.9%vs 63.8%, P=0.002), but a significantly higher incidence of B symptoms (64.3% vs 38.3%, P=0.009), than those patients without this rearrangement. Meanwhile, patients with positive TCRγ gene rearrangement had significantly higher incidence of STAT3 gene mutations (58.3% vs 30.2%, P=0.012). The median follow-up time and overall survival (OS) rate of T-LGLL patients were 43 (3-178) months and 95.1% (98/103), respectively. No significant difference in the OS was observed among the patients with different types of TCR gene clonal rearrangements (all P>0.05) . Conclusion: The detection rate of TCR gene rearrangement for T-cell clones is higher than that of TCRVβ and TRBC1. Patients with positive TCRβ (D-J) gene rearrangement have a higher incidence of B symptoms, lower incidence of autoimmune diseases, and lower HGB levels. Patients with positive TCRγ gene rearrangement are more likely to develop STAT3 gene mutation. These characteristics may be helpful in the differential diagnosis of T-LGLL.

Genetic abnormalities are a cornerstone for prognostic assessment in multiple myeloma (MM) and form the basis of contemporary risk-stratification systems. In routine clinical practice, cytogenetic karyotyping, fluorescence in situ hybridization, and next-generation sequencing should be performed in a standardized manner to identify high-risk patients and guide individualized therapy. With recent advances in genomic technologies, such as whole-genome sequencing and single-cell sequencing, our understanding of clonal evolution and genetic heterogeneity in MM has deepened. Meanwhile, the use of triplet and quadruplet combination regimens has altered the prognostic impact of certain genetic lesions, highlighting the need to update the existing risk frameworks. To standardize genetic testing for MM in China, the Multiple Myeloma Expert Committee of the Chinese Society of Clinical Oncology (CSCO) and Myeloma & Plasma Cell Disease Group, Hematology Oncology Committee of the China Anti-Cancer Association (CACA) have revised the 2019 consensus based on the latest evidence. This updated consensus focuses on refining the testing workflows, harmonizing the interpretation and reporting of high-risk genetic abnormalities, and discussing the incorporation of emerging molecular markers into risk stratification. This new consensus aims to promote standardized and precision-based MM care in China and improve the identification and management of high-risk patients.

Ultraviolet (UV) radiation, one of the critical environmental carcinogenic factors, promotes skin photoaging and carcinogenesis by inducing DNA damage, oxidative stress, and chronic inflammatory cascades. N6-methyladenosine (m6A)-modifying enzymes (writers, erasers, and readers) play bidirectional regulatory roles in UV-mediated skin pathology. In photoaging, the reactive oxygen species (ROS)-m6A axis accelerates collagen degradation and epithelial-mesenchymal transition (EMT) through modulation of matrix metalloproteinases (MMPs), inflammatory mediators, DNA damage repair, apoptosis, and collagen metabolism. In skin cancers, m6A regulators promote tumor progression by influencing oncogenic signaling, proliferation, invasion, metastasis, and immune evasion. Bioactive monomeric compounds derived from traditional Chinese medicine, including polyphenols, saponins, and alkaloids, can regulate the activity of m6A enzymes to interfere with photoaging and UV-induced skin carcinogenesis. This study integrates current evidence to establish an m6A-targeted epigenetic intervention framework for UV-induced skin injury and highlights the potential of synergistic multi-component m6A-modulating therapeutic strategies as a future research priority.

Given the high incidence, poor prognosis, and scarcity of high-quality multimodal research data for acral melanoma in the Chinese population, this study aims to build a representative multimodal disease-specific cohort to provide a high-quality data foundation for characterizing disease features and exploring mechanisms of prognosis.

The occurrence, metastasis, and drug resistance of melanoma pose major challenges to patient prognosis, and predictive models capable of accurately forecasting patient outcomes and guiding treatment are still lacking. This study aims to develop predictive models for melanoma prognosis and drug sensitivity based on mechanisms of programmed cell death (PCD).

Breast cancer is one of the most common malignant tumors in women worldwide, and its high incidence and mortality rate seriously threaten women's health. Studies show that the forkhead box O3a (FoxO3a) plays a key role in the occurrence and progression of breast cancer, particularly in the regulation of apoptosis. As a major member of the FoxO family, FoxO3a exerts tumor-suppressive functions by participating in apoptosis regulation and cell-cycle control. In breast cancer cells, FoxO3a acts as a downstream signaling hub of multiple upstream pathways including phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), mitogen-activated protein kinase (MAPK), and serum- and glucocorticoid-regulated kinase 1 (SGK1). Through nucleocytoplasmic shuttling and alterations in transcriptional activity, FoxO3a precisely modulates the expression of apoptosis-related target genes such as Bcl-2-interacting mediator of cell death (Bim) and p53-upregulated modulator of apoptosis (PUMA), thereby influencing cell survival or death. In addition, multiple natural compounds and combination therapies can induce apoptosis in breast cancer cells by restoring or enhancing FoxO3a activity, and may partially overcome treatment resistance. Systematic elucidation of the complexity of the FoxO3a signaling network and its dual roles in breast cancer therapy may provide theoretical support for understanding tumor-drug resistance mechanisms and for developing precision therapeutic strategies targeting FoxO3a nodes. Future research should further clarify the functional differences among FoxO3a splice variants and FoxO family members, reveal the molecular basis of FoxO3a functional switching in the tumor microenvironment, and promote the clinical translation of biomarkers and targeted drugs.