1.EZH2 promotes malignant biological behavior in esophageal squamous cell carcinoma via EMT.
Yuying JING ; Kaige YANG ; Yiting CHENG ; Tianping HUANG ; Sufang CHEN ; Kai CHEN ; Jianming HU
Journal of Central South University(Medical Sciences) 2025;50(2):155-166
OBJECTIVES:
Esophageal squamous cell carcinoma (ESCC) is characterized by complex pathogenesis and poor prognosis. In recent years, epithelial-mesenchymal transition (EMT) in tumor initiation and progression has attracted increasing attention. Enhancer of zeste homolog 2 (EZH2), which is aberrantly expressed in various tumors, may be closely related to the EMT process. This study aims to examine the expression and correlation of EZH2 and EMT markers in ESCC cells and tissues, evaluate the effects of EZH2 knockdown on ESCC cell proliferation, invasion, and migration, and explore how EZH2 contributes to the malignant biological behavior of ESCC.
METHODS:
Bioinformatics analyses were used to assess EZH2 expression levels in ESCC. Small interfering RNA was used to knock down EZH2 in ESCC cell lines EC109 and EC9706. Cell proliferation, invasion, and migration were evaluated using cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Protein and mRNA expression levels of EZH2, E-cadherin (E-cad), and vimentin (Vim) were detected by Western blotting and real time fluorogenic quantitative PCR (RT-qPCR), respectively. Immunohistochemical (IHC) staining was performed on 70 ESCC tissue samples and 40 paired adjacent normal tissues collected from the First Affiliated Hospital of Shihezi University between 2010 and 2016 to assess the expression of EZH2, E-cad, and Vim, and to analyze their associations with clinicopathological feature and patient prognosis.
RESULTS:
Bioinformatics analysis showed that EZH2 was highly expressed in ESCC (P<0.001), and high EZH2 expression was associated with worse prognosis (P<0.001). CCK-8, wound healing, and Transwell assays demonstrated that EZH2 knockdown significantly suppressed the proliferation, invasion, and migration of ESCC cells (P<0.001). In addition, Vim expression was significantly reduced, while E-cad expression was significantly increased at both protein and mRNA levels in EZH2-silenced cells (all P<0.05). IHC staining analysis revealed higher expression of EZH2 and Vim and lower expression of E-cad in ESCC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that low expression of EZH2 and Vim and high expression of E-cad were associated with longer survival (all P<0.05).
CONCLUSIONS
EZH2 promotes malignant biological behavior in ESCC by mediating EMT. Elevated EZH2 expression is associated with poor prognosis in ESCC patients.
Humans
;
Enhancer of Zeste Homolog 2 Protein/physiology*
;
Esophageal Squamous Cell Carcinoma/pathology*
;
Epithelial-Mesenchymal Transition/genetics*
;
Esophageal Neoplasms/metabolism*
;
Cell Proliferation
;
Cell Line, Tumor
;
Cell Movement
;
Cadherins/genetics*
;
Vimentin/genetics*
;
Male
;
Female
;
Middle Aged
;
Neoplasm Invasiveness
;
Prognosis
;
RNA, Small Interfering/genetics*
;
Gene Expression Regulation, Neoplastic
2.N6-methyladenosine modification and skin diseases.
Ling JIANG ; Yibo HU ; Jing CHEN
Journal of Central South University(Medical Sciences) 2025;50(3):382-395
Currently, research on N6-methyladenine (m6A) is extensive in the field of oncology, while studies involving m6A and skin diseases remain relatively limited. Based on existing reports, we searched PubMed and Web of Science for literature related to m6A and dermatological conditions. Analysis of citation counts and journal impact factors revealed a significant upward trend in the volume of m6A-related research. Term frequency analysis of titles and abstracts indicated that studies mainly focus on skin tumors and inflammatory or immune-related skin diseases, particularly melanoma, psoriasis, and skin development. Transcriptomic data from the Gene Expression Omnibus (GEO) were analyzed, revealing differential expression of m6A-related genes in 4 types of skin tumors (including squamous cell carcinoma and basal cell carcinoma) as well as in inflammatory skin diseases such as psoriasis and atopic dermatitis, and potential mechanisms of action were also explored. Findings suggest that m6A modifications exhibit heterogeneity between neoplastic and non-neoplastic skin diseases. However, the regulatory mechanisms of m6A dynamic modifications on key genes involved in dermatological disorders remain unclear and warrant further investigation.
Humans
;
Skin Neoplasms/metabolism*
;
Skin Diseases/metabolism*
;
Adenosine/genetics*
;
Psoriasis/genetics*
;
Carcinoma, Squamous Cell/genetics*
;
Carcinoma, Basal Cell/genetics*
;
Melanoma/genetics*
3.Successful in situ 5-aminolevulinic acid photodynamic therapy in a 53-year-old female with cutaneous squamous cell carcinoma.
Limin LUO ; Xiaoling JIANG ; Jianjun QIAO ; Hong FANG ; Jun LI
Journal of Zhejiang University. Science. B 2025;26(9):915-922
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans
;
Aminolevulinic Acid/therapeutic use*
;
Skin Neoplasms/pathology*
;
Photochemotherapy/methods*
;
Female
;
Carcinoma, Squamous Cell/pathology*
;
Middle Aged
;
Photosensitizing Agents/therapeutic use*
;
Carcinoma, Basal Cell/drug therapy*
4.Clinical treatment strategy for pT3N0 laryngeal squamous cell carcinoma.
Chuan LIU ; Wei MA ; Zhihai WANG ; Yanshi LI ; Min PAN ; Quan ZENG ; Guohua HU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(1):61-65
Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma(SCC). Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival(OS), disease specific survival(DSS) and disease-free survival(DFS) were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group(Log-rank=0.184, 0.010 and 0.051, P>0.05). Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group(Log-rank=0.214, 0.251 and 0.003, P>0.05). Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group(Log-rank=7.338, P=0.007). The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant(Log-rank=0.895 and 1.792; P>0.05). The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group(Log-rank=7.172, P=0.007), but there were no significant differences in OS and DSS between these two groups(Log-rank=0.010 and 0.876, P>0.05). Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans
;
Laryngeal Neoplasms/therapy*
;
Laryngectomy/methods*
;
Retrospective Studies
;
Carcinoma, Squamous Cell/surgery*
;
Male
;
Female
;
Middle Aged
;
Disease-Free Survival
;
Neoplasm Staging
;
Aged
;
Survival Rate
;
Treatment Outcome
5.Nasolabial groove through the skin flap repair nasal vestibular benign and malignant lesions Application of postoperative tissue defects.
Tongtong GUO ; Sitong GE ; Sijiao SHAN ; Meishan LIU ; Fuyu WANG ; Xian JIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(3):265-271
Objective:To investigate the application value of nasolabial flaps in addressing tissue defects after resection of benign and malignant nasal vestibular lesions. Methods:The clinical data of patients with benign and malignant nasal vestibular lesions were analyzed retrospectively. There were 4 cases of squamous cell carcinoma, 2 cases of black hairy nevus and 1 case of chronic proliferative inflammatory lesions, all of which were repaired by adjacent nasolabial flap. Results:After 6 months of follow-up, none of the patients developed nasal vestibular contracture or nostril stenosis, and postoperative nasal ventilation function was good. Conclusion:The preoperative design of individual nasolabial flaps is very important for maintaining maxillofacial aesthetics, protectingthe nasolabial framework, and preserving postoperative nasal ventilation function.
Humans
;
Retrospective Studies
;
Middle Aged
;
Nose Neoplasms/surgery*
;
Surgical Flaps
;
Male
;
Female
;
Adult
;
Nose/surgery*
;
Plastic Surgery Procedures/methods*
;
Carcinoma, Squamous Cell/surgery*
;
Aged
;
Skin Transplantation
6.Research progress on the mechanisms of resistance to cetuximab targeted therapy in head and neck squamous cell carcinoma.
Lulu LIU ; Dan LUO ; Wenqing ZHANG ; Zhenfeng SUN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(6):582-589
Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor (EGFR) and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans
;
Cetuximab/therapeutic use*
;
Drug Resistance, Neoplasm
;
Squamous Cell Carcinoma of Head and Neck/drug therapy*
;
Head and Neck Neoplasms/drug therapy*
;
ErbB Receptors/metabolism*
;
Tumor Microenvironment
;
Epithelial-Mesenchymal Transition
;
Molecular Targeted Therapy
;
Antineoplastic Agents, Immunological/therapeutic use*
7.Integrated imaging and clinical features of glottic squamous cell carcinoma of the larynx: pathological association and prognosis assessment.
Yuqiao ZHANG ; Wulin WEN ; Fengxia YANG ; Dongke MA ; Xueliang SHEN ; Ningyu FENG ; Xixi LI ; Zhiling ZENG ; Zhipeng MI ; Xiyuan YAN ; Ruixia MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(8):709-716
Objective:To explore the clinical, imaging, and pathological features of glottic squamous cell carcinoma of the larynx and their relationship with prognosis. Methods:A retrospective analysis was conducted on the clinical, imaging, and pathological data of 130 patients with glottic squamous cell carcinoma of the larynx who were treated at the First People's Hospital of Yinchuan and the General Hospital of Ningxia Medical University from January 2018 to March 2023. Imaging examinations (CT and MRI) were used to evaluate the lesion boundary clarity, density, enhancement nature, and enhancement degree. Postoperative pathological examination was used to determine the pathological nature, immunohistochemistry, etc. Statistical methods such as χ² test, Spearman correlation analysis, multivariate logistic regression analysis, and Kaplan-Meier method were used to analyze the data. Results:Among the 130 patients, 127 were male and 3 were female, with an average age of (61.92±9.595) years. There was a correlation between clinical, imaging, and pathological features. Multivariate analysis showed that heterogeneous MRI density (OR=12.414;P=0.019) and squamous cell carcinoma as a subtype were correlated. The initial symptom of non-hoarseness (HR=6.045;P=0.010) and unclear MRI boundary (HR=12.559; P=0.029) were independent risk factors for poor prognosis in patients with glottic squamous cell carcinoma of the larynx. Conclusion:There is a correlation between the clinical, imaging, and pathological features of patients with glottic squamous cell carcinoma of the larynx, and they can affect prognosis. The initial symptom of non-hoarseness and unclear MRI boundary of the tumor are independent risk factors for poor prognosis.
Humans
;
Laryngeal Neoplasms/diagnosis*
;
Prognosis
;
Male
;
Female
;
Retrospective Studies
;
Middle Aged
;
Carcinoma, Squamous Cell/diagnosis*
;
Magnetic Resonance Imaging
;
Glottis/pathology*
;
Tomography, X-Ray Computed
;
Aged
8.Application of different repair methods for defects after Mohs micrographic surgery for malignant tumors of the external nose.
Huilin LI ; Mei ZHENG ; Xiaolin WANG ; Huan QI ; Zhifei ZHANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(9):830-835
Objective:To observe the effects of different repair methods in the defects after Mohs surgical excision of malignant nasal tumors. Methods:Twenty-two cases of external nasal malignant tumor surgery from January 2021 to May 2024 were selected as the research. The tumors were resected using Mohs surgical technique, and the defects were repaired using forehead axial flap, bipedicle flap, nasolabial flap, free full-thickness skin graft from the groin, forehead axial flap, facial kite flap, and composite flap of earlobe cartilage and perichond. The postoperative flap survival, external nasal morphology, and tumor recurrence were observed. Results:Among the 22 cases, there were 1 case of Kaposis sarcoma(KS), 2 cases of squ cell carcinoma, and 19 cases of basal cell carcinoma. Tumors were located at the nasal root in 3 cases, the nasal dorsum in5 cases, the nasal tip in 2 cases, the ala in 8 cases, both the ala and the nasal dorsum in 2 cases, nasal columella, the nasal tip, and the ala in 1 case, the nasal tip, the nasal dorsum, the ala, and paranasal area in 1 case. The size of the defects ranged from 1.2 cm×1.4 cm to 3.7 cm×4.8 cm. Three cases were repaired with forehead axial flaps, four cases with bilobed flaps, thirteen cases with nasolabial groove flaps, one case with free full-thickness skin grafts from the inguinal region, and one case with a combination of forehead axial flaps and facial kite flaps plus a composite of earlobe cartilage and perichondrium. All flaps survived well after surgery. Patients were followed up for 6 months to 3 years after surgery, during which no tumor recurrence was observed, and most patients were satisfied with appearance of their nose. Conclusion:Mohs surgery is used to excise the malignant tumor of the external nose, and satisfactory surgical results can be obtained by using different repair methods based the location and size of the postoperative defect.
Humans
;
Mohs Surgery/methods*
;
Nose Neoplasms/surgery*
;
Surgical Flaps
;
Skin Transplantation
;
Male
;
Carcinoma, Basal Cell/surgery*
;
Skin Neoplasms/surgery*
;
Female
;
Middle Aged
;
Plastic Surgery Procedures/methods*
;
Nose/surgery*
;
Aged
;
Adult
;
Carcinoma, Squamous Cell/surgery*
9.Development and validation of a nomogram for predicting cervical lymph node metastasis based on hematological parameters and clinicopathological characteristics in patients with laryngeal squamous cell carcinoma.
Shanshan TIAN ; Yu SONG ; Ningyuan WANG ; Jianqiang LI ; Wenwen CHEN ; Deli WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(10):949-956
Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis(CLNM) in patients with laryngeal squamous cell carcinoma(LSCC), and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein(CRP), fibrinogen, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), systemic immune-inflammation index(SII), systemic inflammation response index(SIRI), and prognostic inflammatory index(PIV) between the CLNM-positive and CLNM-negative groups(P<0.05). Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width(RDW) -coefficient of variation(RDW-CV), CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio(LMR) were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients(P<0.05). A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837(95%CI 0.766-0.908) in the training cohort and 0.809(95%CI 0.698-0.920) in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans
;
Nomograms
;
Laryngeal Neoplasms/blood*
;
Retrospective Studies
;
Lymphatic Metastasis
;
Carcinoma, Squamous Cell/blood*
;
Lymph Nodes/pathology*
;
Male
;
Female
;
Middle Aged
;
Neck
;
C-Reactive Protein
;
Aged
;
Logistic Models
;
Neutrophils
;
Prognosis
10.Exploration of clear surgical margin in human papillomavirus positive oropharyngeal cancer treated with transoral robotic surgery.
Hongli GONG ; Chengzhi XU ; Chunping WU ; Pengyu CAO ; Yongzheng CHEN ; Jianfang WU ; Meiqin SHI ; Ming ZHANG ; Liang ZHOU ; Lei TAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(11):1016-1027
Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery(TORS) in treating human papillomavirus(HPV) -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage(≤T3 stage) oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival(OS) and progression-free survival(PFS). Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients(60 males, 66.7%) were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years(range: 39-84 years) old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender(P>0.05). Cox analysis identified surgical margins>2 mm as a significant factor improving PFS(HR=0.14, 95%CI 0.02-0.90, P=0.038). Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Male
;
Middle Aged
;
Carcinoma, Squamous Cell/virology*
;
Human Papillomavirus Viruses/isolation & purification*
;
Margins of Excision
;
Oropharyngeal Neoplasms/virology*
;
Papillomavirus Infections/virology*
;
Prognosis
;
Prospective Studies
;
Robotic Surgical Procedures/methods*

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