1.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
Purpose:
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.
Methods:
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results:
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
2.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
Purpose:
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.
Methods:
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results:
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
3.Zinc Finger Protein 639 Expression Is a Novel Prognostic Determinant in Breast Cancer
Fang LEE ; Shih-Ping CHENG ; Ming-Jen CHEN ; Wen-Chien HUANG ; Yi-Min LIU ; Shao-Chiang CHANG ; Yuan-Ching CHANG
Journal of Breast Cancer 2025;28(2):86-98
Purpose:
Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized.
Methods:
Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection.
Results:
Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20.
Conclusion
Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.
4.Long-Term Assessment of Speech and Swallowing Function in Laryngopharyngeal Cancer Patients After J-Flap Reconstruction
Yi-An LU ; Chung-Kan TSAO ; Li-Jen HSIN ; Hsiu-Feng CHUANG ; Tuan-Jen FANG
Clinical and Experimental Otorhinolaryngology 2024;17(4):346-354
Objectives:
. A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time.
Methods:
. Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death.
Results:
. Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively).
Conclusions
. This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.
5.Long-Term Assessment of Speech and Swallowing Function in Laryngopharyngeal Cancer Patients After J-Flap Reconstruction
Yi-An LU ; Chung-Kan TSAO ; Li-Jen HSIN ; Hsiu-Feng CHUANG ; Tuan-Jen FANG
Clinical and Experimental Otorhinolaryngology 2024;17(4):346-354
Objectives:
. A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time.
Methods:
. Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death.
Results:
. Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively).
Conclusions
. This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.
6.Long-Term Assessment of Speech and Swallowing Function in Laryngopharyngeal Cancer Patients After J-Flap Reconstruction
Yi-An LU ; Chung-Kan TSAO ; Li-Jen HSIN ; Hsiu-Feng CHUANG ; Tuan-Jen FANG
Clinical and Experimental Otorhinolaryngology 2024;17(4):346-354
Objectives:
. A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time.
Methods:
. Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death.
Results:
. Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively).
Conclusions
. This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.
7.Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation
Ying-Nan TSAI ; Jia-Ling WU ; Cheng-Hao TSENG ; Tzu-Haw CHEN ; Yi-Ling WU ; Chieh-Chang CHEN ; Yu-Jen FANG ; Tzeng-Huey YANG ; Mindie H. NGUYEN ; Jaw-Town LIN ; Yao-Chun HSU
Clinical and Molecular Hepatology 2024;30(1):98-108
Background/Aims:
Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR).
Methods:
This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR.
Results:
The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5–40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7–67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1–62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12–2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21–0.81).
Conclusions
Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.
8.Differences in major adverse cardiovascular events of metabolic dysfunction-associated steatotic liver disease by race and ethnicity: Letter to the editor on “Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study”
Hui-Chin CHANG ; Wen-Chieh LIAO ; Yi-Jen FANG ; Shiu-Jau CHEN ; Shuo-Yan GAU
Clinical and Molecular Hepatology 2024;30(4):978-981
9.Pathophysiological Mechanisms Underlying Unilateral Vocal Fold Paralysis in Female Patients: An Ultrasonographic Study
Yi-An LU ; Yun-Chen TSAI ; Wan-Ni LIN ; Yu-Cheng PEI ; Tuan-Jen FANG
Clinical and Experimental Otorhinolaryngology 2023;16(4):395-402
Objectives:
. Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal fold paralysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFP patients to investigate the pathophysiologic mechanisms of UVFP.
Methods:
. In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measured using B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode.
Results:
. Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA) muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respectively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side, as observed through LEMG, correlated with the VF length during the resting phase (R=0.368, P=0.050) and CDVL values (R=0.627, P=0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlated with the normalized phonatory vocal length change (nPLC; R=0.621, P=0.041) on the paralyzed side.
Conclusion
. CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFP cases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The findings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngeal nerve injury and offer valuable insights into the pathophysiology of UVFP.
10.Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis
Chen-Hua LIU ; Chi-Yi CHEN ; Wei-Wen SU ; Chun-Jen LIU ; Ching-Chu LO ; Ke-Jhang HUANG ; Jyh-Jou CHEN ; Kuo-Chih TSENG ; Chi-Yang CHANG ; Cheng-Yuan PENG ; Yu-Lueng SHIH ; Chia-Sheng HUANG ; Wei-Yu KAO ; Sheng-Shun YANG ; Ming-Chang TSAI ; Jo-Hsuan WU ; Po-Yueh CHEN ; Pei-Yuan SU ; Jow-Jyh HWANG ; Yu-Jen FANG ; Pei-Lun LEE ; Chi-Wei TSENG ; Fu-Jen LEE ; Hsueh-Chou LAI ; Tsai-Yuan HSIEH ; Chun-Chao CHANG ; Chung-Hsin CHANG ; Yi-Jie HUANG ; Jia-Horng KAO
Clinical and Molecular Hepatology 2021;27(4):575-588
Background/Aims:
Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited.
Methods:
We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported.
Results:
The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001).
Conclusions
SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

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