1.Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonisticallymodulating CCL18.
Qianyu BI ; Mengran WANG ; Li LUO ; Beiying ZHANG ; Siyuan LV ; Zengna WANG ; Xuming JI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):838-847
Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects*
;
Carcinoma, Non-Small-Cell Lung/metabolism*
;
Humans
;
Animals
;
Lung Neoplasms/metabolism*
;
Chemokines, CC/antagonists & inhibitors*
;
Mice
;
Mice, Nude
;
Drugs, Chinese Herbal/administration & dosage*
;
Cell Line, Tumor
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Neoplasm Metastasis
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Tumor-Associated Macrophages/drug effects*
;
Mice, Inbred BALB C
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Signal Transduction/drug effects*
2.TSZAF monomer combination downregulates the Wnt/β-catenin signaling pathway and inhibits neutrophil recruitment to prevent lung cancer metastasis.
Pan YU ; Jialiang YAO ; Long ZHANG ; Yanhong WANG ; Xinyi LU ; Jiajun LIU ; Zujun QUE ; Yao LIU ; Qian BA ; Jiwei LIU ; Yan WU ; Jianhui TIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1069-1079
Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics*
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Wnt Signaling Pathway/drug effects*
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Animals
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Humans
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Drugs, Chinese Herbal/pharmacology*
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Mice
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Neoplasm Metastasis/prevention & control*
;
Cell Proliferation/drug effects*
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Cell Line, Tumor
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Neutrophil Infiltration/drug effects*
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Down-Regulation/drug effects*
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Cell Movement/drug effects*
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beta Catenin/genetics*
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Apoptosis/drug effects*
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Mice, Inbred C57BL
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Male
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Neoplastic Cells, Circulating/drug effects*
3.Multidisciplinary expert consensus on thermal ablation for benign thyroid diseases, low-risk thyroid carcinoma, and metastatic cervical lymph nodes (2025 edition).
Chinese Journal of Internal Medicine 2025;64(7):614-624
Thermal ablation has proven an effective treatment modality for certain thyroid diseases. However, its indications remain the subject of significant debate both domestically and internationally. Over recent years, several international academic organizations have issued consensus statements, position papers, and guidelines concerning thyroid thermal ablation. In China, the Chinese College of Interventionalists (CCI), in collaboration with other relevant academic organizations, released the "Expert consensus on thermal ablation for thyroid benign nodes, microcarcinoma and metastatic cervical lymph nodes (2018 edition)". This consensus statement received widespread recognition within the field and contributed significantly to the standardization of thyroid thermal ablation therapy in China. With the continuous accumulation of evidence-based medical data, the need for a more stringent and standardized approach to thyroid thermal ablation has become evident. Accordingly, the Interventional Ultrasound Committee of the CCI, in collaboration with multiple academic organizations and experts, conducted extensive discussions and multiple revisions before finalizing the "Multidisciplinary expert consensus on thermal ablation for benign thyroid diseases, low-risk thyroid carcinoma, and metastatic cervical lymph nodes (2025 edition)". This updated consensus builds on the framework of the 2018 edition, refining indications and contraindications, emphasizing standardized treatment, and outlining future directions for research and clinical applications of thyroid thermal ablation technology.
Humans
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Thyroid Neoplasms/surgery*
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Consensus
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Lymphatic Metastasis
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Lymph Nodes/pathology*
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Thyroid Diseases/surgery*
4.miR-302a-3p targeting lysosomal-associated membrane protein 5 inhibits the invasion and metastasis of oral squamous cell carcinoma.
Li YU ; Tiejun ZHOU ; Xiao WU ; Xinhong LIN ; Xiaoyan ZHANG ; Yongxian LAI ; Xinyue LIAO ; Hang SI ; Yun FENG ; Jie JIAN ; Yan FENG
West China Journal of Stomatology 2025;43(4):547-558
OBJECTIVES:
This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC.
METHODS:
The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model.
RESULTS:
LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor.
CONCLUSIONS
LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism*
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Mouth Neoplasms/metabolism*
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Humans
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Animals
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Carcinoma, Squamous Cell/genetics*
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Neoplasm Invasiveness
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Cell Proliferation
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Mice, Nude
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Cell Movement
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Lysosomal Membrane Proteins/genetics*
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Mice
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Cell Line, Tumor
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Neoplasm Metastasis
5.Lymphatic and Venous Contrast-Enhanced Ultrasound Imaging for Differential Diagnosis of Cervical Lymph Node Metastasis in Thyroid Cancer.
Li XU ; Wen-Bo WAN ; Tian GAO ; Tao-Hua GOU ; Yan ZHANG
Acta Academiae Medicinae Sinicae 2025;47(1):16-22
Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans
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Thyroid Neoplasms/diagnostic imaging*
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Lymphatic Metastasis/diagnostic imaging*
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Diagnosis, Differential
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Female
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Male
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Middle Aged
;
Ultrasonography
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Adult
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Lymph Nodes/pathology*
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Contrast Media
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Neck
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Aged
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Young Adult
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Adolescent
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Sensitivity and Specificity
6.Ultrasound Characteristics of Secondary Squamous Cell Carcinoma of the Thyroid.
Dong LIU ; Yan-Jia GOU ; Quan WEN ; Su-Ting ZONG
Acta Academiae Medicinae Sinicae 2025;47(3):390-395
Objective To analyze the ultrasonographic features of secondary squamous cell carcinoma of the thyroid(SSCC-T)and evaluate the diagnostic value of ultrasound.Methods A retrospective analysis was conducted on clinical and ultrasonographic data from 12 patients with pathologically confirmed SSCC-T treated at Beijing Friendship Hospital,Capital Medical University between January 2016 and January 2025.Evaluated parameters included lesion size,echogenicity,edge,vascularity,calcification,and cervical lymph node metastasis.Descriptive statistical analysis was performed to analyze the ultrasonographic features of SSCC-T,and Fisher's exact test was conducted to analyze the correlation between different ultrasound classifications and thyroid dysfunction.Results The 12 patients showed the following ultrasound classifications:nodular type(50.0%,6/12),diffuse type(33.3%,4/12),and mixed type(16.7%,2/12).All diffuse-type patients exhibited a characteristic cord-like hypoechoic pattern.Cervical lymph node metastasis was observed in all the patients,with 75.0%(9/12)showing lymph nodes >2 cm in maximum diameter.Thyroid dysfunction occurred in 66.7%(8/12)of patients,including 2 patients with dynamic shifts from hyperthyroidism to hypothyroidism.Diffuse and mixed types were associated with hypothyroidism(P=0.038).Conclusions SSCC-T demonstrates specific ultrasonographic features,particularly the cord-like hypoechoic pattern in the diffuse type.For patients with squamous cell carcinoma,regular ultrasound examinations of the thyroid and cervical lymph nodes combined with changes in thyroid function are conducive to the timely detection of thyroid metastasis of squamous cell carcinoma.
Humans
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Retrospective Studies
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Ultrasonography
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Carcinoma, Squamous Cell/diagnostic imaging*
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Thyroid Neoplasms/diagnostic imaging*
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Lymphatic Metastasis
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Male
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Female
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Middle Aged
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Thyroid Gland/diagnostic imaging*
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Adult
7.Value of Ultrasonographic Features Combined With Immunohistochemistry in Predicting Axillary Lymph Node Metastasis in Middle-Aged Women With Breast Cancer.
Qian-Kun CHANG ; Wen-Ying WU ; Chun-Qiang BAI ; Zhi-Chao DING ; Wei-Fang WANG ; Ming-Han LIU
Acta Academiae Medicinae Sinicae 2025;47(4):550-556
Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans
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Female
;
Breast Neoplasms/diagnostic imaging*
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Middle Aged
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Lymphatic Metastasis/diagnostic imaging*
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Axilla
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Retrospective Studies
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Nomograms
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Ultrasonography
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Immunohistochemistry
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Lymph Nodes/diagnostic imaging*
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Risk Factors
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Ki-67 Antigen
8.Potential molecular mechanism of lncRNAs HOTAIR in malignant metastasis of esophageal cancer.
Kaijin LU ; Jiangfeng SHEN ; Guang HAN ; Quan CHEN
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):236-244
Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans
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RNA, Long Noncoding/metabolism*
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Esophageal Neoplasms/metabolism*
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Cell Movement/genetics*
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Cell Proliferation/genetics*
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Cell Line, Tumor
;
Esophageal Squamous Cell Carcinoma
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Exosomes/genetics*
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Neoplasm Metastasis
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Neoplasm Invasiveness
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Gene Expression Regulation, Neoplastic
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Glycolysis/genetics*
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Cancer-Associated Fibroblasts/metabolism*
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Carcinoma, Squamous Cell/metabolism*
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Cadherins/genetics*
9.Phospholipase Cβ1 (PLCB1) promotes gastric adenocarcinoma metastasis by inducing epithelial mesenchymal transition and inhibiting tumour immune infiltration and is associated with poor patient prognosis.
Lingping YUE ; Junfeng CHEN ; Qianqian GAO
Chinese Journal of Cellular and Molecular Immunology 2025;41(5):444-449
Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8+ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8+ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8+ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8+ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.
Humans
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Stomach Neoplasms/genetics*
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Epithelial-Mesenchymal Transition
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Male
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Female
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Middle Aged
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Prognosis
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Adenocarcinoma/genetics*
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Cadherins/metabolism*
;
Aged
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Adult
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CD8-Positive T-Lymphocytes/immunology*
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Vimentin/metabolism*
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Lymphatic Metastasis
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Neoplasm Metastasis
10.Plasma lipidomics-based exploration of potential biomarkers of metastasis in pediatric medulloblastoma.
Chun-Jing YANG ; Xi-Qiao XU ; Li BAO ; Wan-Shui WU ; De-Chun JIANG ; Zheng-Yuan SHI
Chinese Journal of Contemporary Pediatrics 2025;27(11):1384-1390
OBJECTIVES:
To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children.
METHODS:
In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance.
RESULTS:
Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype.
CONCLUSIONS
Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans
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Medulloblastoma/diagnosis*
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Lipidomics
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Child
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Male
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Female
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Child, Preschool
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Cerebellar Neoplasms/blood*
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Biomarkers, Tumor/blood*
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Neoplasm Metastasis
;
Prospective Studies
;
Adolescent
;
Lipids/blood*

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