22 results on '"Peng, Yong"'
Search Results
2. Angiotensin-converting enzyme inhibitor for post-transcatheter aortic valve implantation patients: study protocol for a multicenter randomized, open-label blinded endpoint control trial
- Author
-
Liao, Yan Biao, Xia, Congying, Cheng, Yiheng, Li, Qiao, Wei, Xin, Ou, Yuanweixiang, Chen, Fei, Li, Yijian, Liu, Qi, Xiong, Tianyuan, Zhao, Zhengang, Peng, Yong, Wei, Jiafu, Feng, Yuan, and Chen, Mao
- Published
- 2021
- Full Text
- View/download PDF
3. Association of fine particulate matter exposure with acute noncardiovascular critical illnesses and in-hospital outcomes in patients receiving intensive cardiac care
- Author
-
Chen, Fei, Liu, Qi, Huang, Baotao, Huang, Fangyang, Li, Yiming, Peng, Yong, and Chen, Mao
- Published
- 2020
- Full Text
- View/download PDF
4. The triglyceride paradox in the mortality of coronary artery disease
- Author
-
Xia, Tian-li, Li, Yi-ming, Huang, Fang-yang, Chai, Hua, Huang, Bao-tao, Li, Qiao, Zhao, Zhen-gang, Liao, Yan-biao, Zuo, Zhi-liang, Peng, Yong, Chen, Mao, and Huang, De-jia
- Published
- 2019
- Full Text
- View/download PDF
5. Influence of age on the effect of reduced renal function on outcomes in patients with coronary artery disease
- Author
-
Chen, Fei, Zuo, Zhi-liang, Huang, Fang-yang, Xia, Tian-li, Huang, Bao-tao, Chai, Hua, Li, Qiao, Pu, Xiao-bo, Gui, Yi-yue, Peng, Yong, Chen, Mao, and Huang, De-jia
- Published
- 2019
- Full Text
- View/download PDF
6. CDCA5 overexpression is an Indicator of poor prognosis in patients with hepatocellular carcinoma (HCC)
- Author
-
Tian, Yunhong, Wu, Jianlin, Chagas, Cristian, Du, Yichao, Lyu, Huan, He, Yunhong, Qi, Shouliang, Peng, Yong, and Hu, Jiani
- Published
- 2018
- Full Text
- View/download PDF
7. '3G' Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy
- Author
-
Erwin Tantoso, Matthew C.H. Ng, Wei Peng Yong, Angie Lay Keng Tan, Jimmy Bok Yan So, Patrick Tan, Ming Hui Lee, Henry Yang, Omer An, Sun Young Rha, Raghav Sundar, Xuewen Ong, Leilei Chen, Su Ting Tay, Yangyang Song, and Xinyu Ke
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Cancer chemotherapy ,medicine.medical_treatment ,In silico ,Adenocarcinoma ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Stomach Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Clinical Trials as Topic ,Chemotherapy ,business.industry ,Gene Expression Profiling ,Cancer ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Gene expression profiling ,030104 developmental biology ,RNA editing ,030220 oncology & carcinogenesis ,RNA Editing ,Cancer development ,Neoplasm Recurrence, Local ,business - Abstract
Gastric cancer cases are often diagnosed at an advanced stage with poor prognosis. Platinum-based chemotherapy has been internationally accepted as first-line therapy for inoperable or metastatic gastric cancer. To achieve greater benefits, selection of patients eligible for this treatment is critical. Although gene expression profiling has been widely used as a genomic classifier to identify molecular subtypes of gastric cancer and to stratify patients for different chemotherapy regimens, its prediction accuracy can be improved. Adenosine-to-inosine (A-to-I) RNA editing has emerged as a new player contributing to gastric cancer development and progression, offering potential clinical utility for diagnosis and treatment. Using a systematic computational approach followed by both in vitro validations and in silico validations in The Cancer Genome Atlas (TCGA), we conducted a transcriptome-wide RNA editing analysis of a cohort of 104 patients with advanced gastric cancer and identified an RNA editing (GCRE) signature to guide gastric cancer chemotherapy. RNA editing events stood as a prognostic and predictive biomarker in advanced gastric cancer. A GCRE score based on the GCRE signature consisted of 50 editing sites associated with 29 genes, predicting response to chemotherapy with a high accuracy (84%). Of note, patients demonstrating higher editing levels of this panel of sites presented a better overall response. Consistently, gastric cancer cell lines with higher editing levels showed higher chemosensitivity. Applying the GCRE score on TCGA dataset confirmed that responders had significantly higher levels of editing in advanced gastric cancer. Overall, this newly defined GCRE signature reliably stratifies patients with advanced gastric cancer and predicts response from chemotherapy. Significance: This study describes a novel A-to-I RNA editing signature as a prognostic and predictive biomarker in advanced gastric cancer, providing a new tool to improve patient stratification and response to therapy.
- Published
- 2021
8. Prognostic value of the dynamic hepatorenal function on intermediate‐term mortality in TAVI patients with survival to discharge.
- Author
-
Yao, Yijun, He, Jingjing, Xiong, Tianyuan, Chen, Fei, Ou, Yuanweixiang, Li, Yiming, Liu, Qi, Zhu, Zhongkai, Zhang, Yi, Yang, Haoran, Liang, Yujia, Wei, Xin, Li, Xi, Peng, Yong, Wei, Jiafu, He, Sen, Li, Qiao, Chen, Yong, Meng, Wei, and Chen, Guo
- Subjects
HEART valve prosthesis implantation ,PROGNOSIS ,HOSPITAL admission & discharge ,AORTIC valve ,MORTALITY risk factors - Abstract
Background: Renal and liver dysfunctions are risk factors for mortality in patients with severe aortic stenosis (AS). Transcatheter aortic valve implantation (TAVI) has the potential to break the vicious cycle between AS and hepatorenal dysfunction by relieving aortic valve obstruction. Hypothesis: A part of patients can derive hepatorenal function improvement from TAVI, and this noncardiac benefit improves the intermediate‐term outcomes. Methods: We developed this retrospective cohort study in 439 consecutive patients undergoing TAVI and described the dynamic hepatorenal function assessed by model for end‐stage liver disease model for end‐stage liver disease (MELD)‐XI score in subgroups. The endpoint was 2‐year all‐cause mortality. Results: Receiver‐operating characteristic analysis showed that the baseline MELD‐XI score of 10.71 was the cutoff point. A high MELD‐XI score (>10.71) at baseline was an independent predictor of the 2‐year mortality hazard ratio (HR: 2.65 [1.29–5.47], p =.008). After TAVI, patients with irreversible high MELD‐XI scores had a higher risk of 2‐year mortality than patients who improved from high to low MELD‐XI scores (HR: 2.50 [1.06–5.91], p =.03). Factors associated with reversible MELD‐XI scores improvement were low baseline MELD‐XI scores (≤12.00, odds ratio [OR]: 2.02 [1.04–3.94], p =.04), high aortic valve peak velocity (≥5 m/s, OR: 2.17 [1.11–4.24], p =.02), and low body mass index (≤25 kg/m2, OR: 2.73 [1.25–5.98], p =.01). Conclusion: High MELD‐XI score at baseline is an independent predictor for 2‐year mortality. Patients with hepatorenal function improvement after TAVI have better outcomes. For patients with irreversible hepatorenal dysfunction after TAVI, further optimization of the subsequent treatment after TAVI is needed to improve the outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma
- Author
-
Steven G. Rozen, Heike I. Grabsch, Alvin Wei Tian Ng, William H. Allum, Wen Fong Ooi, Jimmy Bok Yan So, Wei Peng Yong, Patrick Tan, Ruth E Langley, Raghav Sundar, Vivien Koh, Ming Hui Lee, Lindsay C. Hewitt, David Cunningham, Matthew Nankivell, Nisha Padmanabhan, Taotao Sheng, Shenli Zhang, Aditi Qamra, Hermioni Zouridis, Imran Inam, RS: GROW - R2 - Basic and Translational Cancer Biology, Promovendi ODB, and Pathologie
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Esophageal Neoplasms ,SURGERY ,medicine.medical_treatment ,Oesophageal adenocarcinoma ,Epigenesis, Genetic ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Randomized Controlled Trials as Topic ,Aged, 80 and over ,DNA methylation ,METHYLATION ,Middle Aged ,Prognosis ,OPEN-LABEL ,Neoadjuvant Therapy ,Survival Rate ,Predictive biomarker ,030220 oncology & carcinogenesis ,Cohort ,Female ,Fluorouracil ,Adult ,medicine.medical_specialty ,RESECTION ,CAPECITABINE ,Adenocarcinoma ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Chemotherapy ,Epigenetics ,Epigenetic signature ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,business.industry ,PERIOPERATIVE CHEMOTHERAPY ,Cancer ,medicine.disease ,030104 developmental biology ,chemistry ,Cisplatin ,Neoplasm Grading ,business ,DNA ,GASTRIC-CANCER - Abstract
Background: DNA methylation signatures describing distinct histological subtypes of oesophageal cancer have been reported. We studied DNA methylation in samples from the MRC OE02 phase III trial, which randomised patients with resectable oesophageal cancer to surgery alone (S) or neoadjuvant chemotherapy followed by surgery (CS).Aim: The aim of the study was to identify epigenetic signatures predictive of chemotherapy benefit in patients with oesophageal adenocarcinoma (OAC) from the OE02 trial and validate the findings in an independent cohort.Methods: DNA methylation was analysed using the Illumina GoldenGate platform on surgically resected OAC specimens from patients in the OE02 trial. Cox proportional hazard analysis was performed to select probes predictive of survival in the CS arm. Non-negative matrix factorisation was used to perform clustering and delineate DNA methylation signatures. The findings were validated in an independent cohort of patients with gastroesophageal adenocarcinoma treated with neoadjuvant chemotherapy.Results: A total of 229 patients with OAC were analysed from the OE02 trial (118 in the CS arm and 111 in the S arm). There was no difference in DNA methylation status between the CS and S arms. A metagene signature was created by dichotomising samples into two clusters. In cluster 1, patients in the CS arm had significant overall survival (OS) benefit (median OS CS: 931 days vs. S: 536 days [HR: 1.54, P = 0.031]). In cluster 2, patients in the CS arm had similar (or worse) OS compared with patients in the S arm (CS: 348 days vs. S: 472 days [HR: 0.70, P = 0.1], and test of interaction was significant (p = 0.005). In the validation cohort (n = 13), there was no difference in DNA methylation status in paired pre- and post-treatment samples. When the epigenetic signature was applied, cluster 1 samples had better OS (median OS, cluster 1: 1174 days vs. cluster 2: 392 days, HR: 3.47, p = 0.059)Conclusions: This is the first and largest study of DNA methylation in patients with OAC uniformly treated in a randomised phase III trial. We identified an epigenetic signature that may serve as a predictive biomarker for chemotherapy benefit in OAC. (C) 2019 Elsevier Ltd. All rights reserved.
- Published
- 2019
10. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer
- Author
-
Jia Li Low, Yiqing Huang, Wei Peng Yong, Raghav Sundar, K. Spencer, Kenneth Sooi, Yvonne Ang, Boon Cher Goh, Ross A. Soo, Anand D. Jeyasekharan, and Zhi Yao Chan
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Lung cancer ,Aged ,Retrospective Studies ,Response rate (survey) ,Aged, 80 and over ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Confidence interval ,Survival Rate ,030220 oncology & carcinogenesis ,Toxicity ,Female ,business ,Follow-Up Studies - Abstract
A dose of 200 mg 3-weekly of pembrolizumab was approved by the Food and Drug Administration (FDA) as treatment for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2 mg/kg. Our study aimed to assess the efficacy of a lower fixed dose of 100 mg, which is closer to 2 mg/kg weight-based dose in an average-sized Asian patient. All patients receiving pembrolizumab for advanced NSCLC from January 2016 to March 2020 in National University Hospital, Singapore, were included in this retrospective observational study. The effect of pembrolizumab 100 mg (Pem100) vs 200 mg (Pem200) upon survival outcomes, toxicity and cost were examined. One hundred fourteen patients received pembrolizumab. Sixty-five (57%) and 49 (43%) received Pem100 and Pem200, respectively. There was no difference in progression-free survival (PFS) and overall survival (OS) between Pem100 vs Pem200 as a single agent (PFS: 6.8 vs 4.2 months, hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.36-1.46, P = .36; 9 month OS: 58% vs 63%, HR 1.08, 95% CI 0.48-2.41, P = .86) and when combined with chemotherapy (9-month PFS: 60% vs 50%, HR0.84, 95% CI 0.34-2.08, P = .71; 9-month OS: 85% vs 58%, HR 0.27, 95% CI 0.062-1.20, P = .09). No significant difference in response rate or ≥G3 immune-related toxicities between Pem100 and Pem200 was observed. A cost minimisation analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of SGD4,290,912 and cost saving per patient of SGD39,942 in the Pem100 group. A 100 mg of pembrolizumab appears to be effective with reduction in cost. A randomised trial should be done to investigate a lower dose of pembrolizumab.
- Published
- 2021
11. A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours
- Author
-
Lingzhi Wang, Gwo Fuang Ho, Yvonne Ang, Soo-Chin Lee, Bee Choo Tai, Ross A. Soo, Samuel Guan Wei Ow, Joline S.J. Lim, Sing Huang Tan, Wan Qin Chong, Boon Cher Goh, Raghav Sundar, Phyu Pyar Soe, and Wei Peng Yong
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Anti-angiogenic ,Docetaxel ,Tumour vasculature ,Neutropenia ,urologic and male genital diseases ,lcsh:RC254-282 ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Surgical oncology ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Sunitinib ,Genetics ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Lung ,business.industry ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Metastatic breast cancer ,Short-course sunitinib ,Survival Rate ,Advanced solid tumours ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Toxicity ,Female ,business ,Research Article ,Follow-Up Studies ,medicine.drug - Abstract
BackgroundWe previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.MethodsPatients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).ResultsWe enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers.There was no difference in ORR (30.3% vs 28.6%,p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38–3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%,p = 0.027 OR 0.37, 95% CI 0.14–1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15–3.48,p = 0.014) overall, as well as in breast (4.2 vs 5.6 months,p = 0.048) and other cancers (2.0 vs 5.3 months,p = 0.009), but not in lung cancers (2.9 vs 4.1 months,p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51–1.67,p = 0.789), and in the breast (18.9 vs 25.8 months,p = 0.354), lung (7.0 vs 6.7 months,p = 0.970) and other cancers (4.5 vs 8.8 months,p = 0.449) subgroups.Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%,p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%,p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%,p = 0.792).ConclusionsThe addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.Trial registrationThe study was registered (NCT01803503) prospectively on clinicaltrials.gov on 4th March 2013.
- Published
- 2020
12. Identification of Extracellular Matrix Signatures as Novel Potential Prognostic Biomarkers in Lung Adenocarcinoma.
- Author
-
Zeng, Zhen, Zuo, Yuanli, Jin, Yang, Peng, Yong, and Zhu, Xiaofeng
- Subjects
PROGNOSIS ,DISEASE risk factors ,CELL physiology ,ADENOCARCINOMA ,LUNGS - Abstract
The extracellular matrix (ECM) is vital to normal cellular function and has emerged as a key factor in cancer initiation and metastasis. However, the prognostic and oncological values of ECM organization-related genes have not been comprehensively explored in lung adenocarcinoma (LUAD) patients. In this study, we included LUAD samples from The Cancer Genome Atlas (TCGA, training set) and other three validation sets (GSE87340, GSE140343 and GSE115002), then we constructed a three-gene prognostic signature based on ECM organization-related genes. The prognostic signature involving COL4A6 , FGA and FSCN1 was powerful and robust in both the training and validation datasets. We further constructed a composite prognostic nomogram to facilitate clinical practice by integrating an ECM organization-related signature with clinical characteristics, including age and TNM stage. Patients with higher risk scores were characterized by proliferation, metastasis and immune hallmarks. It is worth noting that high-risk group showed higher fibroblast infiltration in tumor tissue. Accordingly, factors (IGFBP5 , CLCF1 and IL6) reported to be secreted by cancer-associated fibroblasts (CAFs) showed higher expression level in the high-risk group. Our findings highlight the prognostic value of the ECM organization signature in LUAD and provide insights into the specific clinical and molecular features underlying the ECM organization-related signature, which may be important for patient treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
13. An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma
- Author
-
Tsu Yi Chao, Manuel Modiano, Wei Peng Yong, Jung Hwan Yoon, Bradley Freilich, Baek Yeol Ryoo, Thomas Yau, Ho Yeong Lim, Chia-Chi Lin, Imane El Dika, Robin Kate Kelley, Jennifer J. Knox, Joanne Brown, Hye Jin Choi, and Ghassan K. Abou-Alfa
- Subjects
Oncology ,Male ,Cancer Research ,02 engineering and technology ,law.invention ,Cohort Studies ,Randomized controlled trial ,law ,Tissue Distribution ,RNA, Small Interfering ,0303 health sciences ,Liver Neoplasms ,Middle Aged ,021001 nanoscience & nanotechnology ,Prognosis ,Lipids ,Hepatocellular carcinoma ,Cohort ,Administration ,Population study ,Administration, Intravenous ,Female ,Patient Safety ,Drug ,0210 nano-technology ,Intravenous ,Cohort study ,Adult ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Maximum Tolerated Dose ,Oncology and Carcinogenesis ,Antineoplastic Agents ,Small Interfering ,Dose-Response Relationship ,03 medical and health sciences ,Pharmacokinetics ,Internal medicine ,medicine ,Carcinoma ,Humans ,Oncology & Carcinogenesis ,030304 developmental biology ,Aged ,Dose-Response Relationship, Drug ,Performance status ,business.industry ,Clinical Trial Results ,Hepatocellular ,medicine.disease ,RNA ,Nanoparticles ,business ,Follow-Up Studies - Abstract
Lessons LearnedTKM-080301 showed a favorable toxicity profile at the studied dose. TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted.
- Published
- 2019
14. Construction of the Prediction Model for Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy Based on Pretreatment Tumor-Infiltrating Macrophage-Associated Biomarkers.
- Author
-
Liu, Xing, Zheng, Shuping, Peng, Yong, Zhuang, Jinfu, Yang, Yuanfeng, Xu, Yunlu, and Guan, Guoxian
- Subjects
RECTAL cancer ,PREDICTION models ,CHEMORADIOTHERAPY ,DECISION making ,REGRESSION analysis ,MULTIVARIATE analysis ,TUMOR-infiltrating immune cells - Abstract
Purpose: To assess the value of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) for predicting the response to neo-chemoradiotherapy (NCRT) and the prognosis of locally advanced rectal cancer (LARC). Methods: We enrolled 191 patients who underwent neoadjuvant chemoradiotherapy and radical resection between 2011 and 2015. Tumor tissues were collected before NCRT with a colonoscope and post-surgery and were subjected to immunohistochemical analysis. Results: The expression levels of macrophage-related biomarkers (CD163, CD68, MCSF, and CCL2) were lower in the pathological complete response (pCR) group when compared with the non-pCR group (all P< 0.05). Based on X-tile plots, we divided the tumors in two groups and found that lower pre-NCRT/post-surgical CD163, CD68, MCSF, CCL2 scores correlated with improved DFS. Cox regression analysis demonstrated that pre-NCRT CD163 (HR=1.008, 95% CI 1.003– 1.013, P=0.003) and MCSF (HR=2.187, 95% CI 1.343– 3.564, P=0.002) scores were independent predictors of DFS. Based on Cox multivariate analysis, we constructed a risk score model with a powerful ability to predict pCR in LARC patients. Moreover, COX regression analysis was performed to explore the role of the risk score in LARC patients. The results demonstrated that tumor size (HR=1.291, P=0.041), worse pathological TNM stage (HR=1.789, P=0.005, and higher risk score (HR=1.084, P< 0.001) were significantly associated with impaired disease-free survival. Based on the above results, a nomogram and decision curve analysis were generated. Conclusion: The expression levels of macrophage-related biomarkers CD163, CD68, MCSF, and CCL2 were associated with chemoradiotherapy resistance and prognosis in LARC patients following NCRT. A risk score model was constructed which could be used to predict LARC outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
15. Controlling Nutritional Status (CONUT) Score as a New Indicator of Prognosis in Patients With Hilar Cholangiocarcinoma Is Superior to NLR and PNI: A Single-Center Retrospective Study.
- Author
-
Wang, Ankang, He, Zhenxing, Cong, Peng, Qu, Yueyu, Hu, Tao, Cai, Yu, Sun, Bo, Chen, Hao, Fu, Wenguang, and Peng, Yong
- Subjects
NUTRITIONAL status ,REFERENCE values ,CHOLANGIOCARCINOMA ,RECEIVER operating characteristic curves ,SURGICAL excision - Abstract
Background: Currently, many nutritional indicators, including controlling nutritional status score (CONUT), can be used to assess a patient's nutritional status and have been reported as reliable predictors of multiple malignancies. However, the value of CONUT score in predicting postoperative outcomes in patients with hilar cholangiocarcinoma has not been explored. In this study, its predictive value will be discussed and compared with the known predictors the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). Methods: Preoperative CONUT scores, PNI and NLR levels of 94 Hilar cholangiocarcinoma (HCCA) patients who underwent radical-intent resection of hepatobiliary surgery in our hospital from March 2010 to April 2019 were retrospectively collected and analyzed. They were grouped according to their optimal cutoff value and the prognostic effects of patients in each group were compared respectively. Results: CONUT
high was more frequent in patients with Clavien–Dindo classification of ≥IIIa (P = 0.008) and Bile leakage presence (P = 0.011). Kaplan-Meier curves analyzing the relationship between CONUT, PNI, and NLR values and HCCA patient survival (including total survival (OS) and recurrence-free survival (RFS) showed significant differences between groups (P <0.001). Meanwhile, multi-factor analysis found that Degree of cure, PNI, NLR, and preoperative CONUT score were independent prognostic factors for OS and RFS. The predictive power of CONUT score was higher than that of NLR and PNI based on time-dependent receiver operating Characteristic (ROC) analysis and the net reclassification index (NRI) and integrated discriminatory index (IDI) values (P < 0.05). Conclusion: CONUT score may be of some clinical reference value in evaluating postoperative prognosis of HCCA patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
16. Diagnostic and prognostic utility of a DNA hypermethylated gene signature in prostate cancer
- Author
-
Liang Kee Goh, Hong Hong Huang, Natalia Liem, Kae Jack Tay, John Soon Wah Low, Gengbo Chen, Aadhitthya Vijayaraghavan, Puay Hoon Tan, Michelle Ker Xing Chang, Adita Joshi, Pei Li Lim, Hong Gee Sim, Wen Son Hsieh, Joshi J. Alumkal, Wei Peng Yong, and Emarene Kalaw
- Subjects
Male ,Oncology ,Microarray ,Microarrays ,Epidemiology ,Prostatic Hyperplasia ,lcsh:Medicine ,Bioinformatics ,Epigenesis, Genetic ,Prostate cancer ,Molecular cell biology ,Prostate ,Pathology ,lcsh:Science ,Oligonucleotide Array Sequence Analysis ,Aged, 80 and over ,Multidisciplinary ,Prostate Cancer ,Cell Differentiation ,Middle Aged ,Prognosis ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,DNA methylation ,Medicine ,Epigenetics ,DNA microarray ,DNA modification ,Research Article ,medicine.medical_specialty ,Biology ,Sensitivity and Specificity ,Asian People ,Diagnostic Medicine ,Internal medicine ,Genetics ,Cancer Detection and Diagnosis ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Proportional hazards model ,Gene Expression Profiling ,lcsh:R ,Computational Biology ,Cancers and Neoplasms ,Prostatic Neoplasms ,Reproducibility of Results ,DNA Methylation ,Gene signature ,medicine.disease ,Gene expression profiling ,Biomarker Epidemiology ,Genitourinary Tract Tumors ,Multivariate Analysis ,lcsh:Q ,Gene expression ,Biomarkers ,General Pathology - Abstract
We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfite-converted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3% and 100% respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8% sensitivity and 66.7% specificity, with overall accuracy of 88.7%. A PHYMA score was developed for each sample based on the state of methylation in the PHYMA signature. Increasing PHYMA score was significantly associated with higher Gleason score and Gleason primary grade. Men with higher PHYMA scores have poorer survival on univariate (p = 0.0038, HR = 3.89) and multivariate analyses when controlled for (i) clinical stage (p = 0.055, HR = 2.57), and (ii) clinical stage and Gleason score (p = 0.043, HR = 2.61). We further performed bisulfite genomic sequencing on 2 relatively unknown genes to demonstrate robustness of the assay results. PHYMA is thus a signature with high sensitivity and specificity for discriminating tumors from BPH, and has a potential role in early detection and in predicting survival.
- Published
- 2014
17. The impact of age on the implementation of evidence-based medications in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.
- Author
-
Xia, Tian-li, Huang, Fang-yang, Li, Yi-ming, Chai, Hua, Huang, Bao-tao, Ou, Yuan-Wei-Xiang, Li, Qiao, Pu, Xiao-bo, Zuo, Zhi-liang, Peng, Yong, Chen, Mao, and Huang, De-jia
- Subjects
CORONARY disease ,EVIDENCE-based medicine ,DISEASE complications ,DISEASE incidence ,PATIENT compliance ,RETROSPECTIVE studies ,PROGNOSIS ,CORONARY heart disease treatment ,AGE distribution ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESEARCH funding ,EVALUATION research - Abstract
Background: Elderly patients with coronary artery disease (CAD) frequently complicated with more cardiovascular risk factors, but received fewer evidence-based medications (EBMs). This study explored the association of EBMs compliance in different age groups and the risk of long-term death.Methods: A retrospective analysis was conducted from a single registered database. 2830 consecutive patients with CAD were enrolled and grouped into 3 categories by age. The primary end point was all-cause mortality and secondary endpoint is cardiovascular mortality.Results: The mean follow-up time was 30.25 ± 11.89 months and death occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival curves indicated that the incidence rates of all-cause death and cardiovascular death increased with age (older than 75 years old vs. 60 to 75 years old vs. younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001; cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of elderly patients using no EBMs was significantly higher than the percentages in the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR] 0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older CAD patients. Similar trends were found about different kinds of EBMs in elderly patients.Conclusions: Elderly patients with CAD had higher risk of death but a lower degree of compliance with EBMs usage. Elderly CAD patients could receive more clinical benefits by using EBMs. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
18. Recent progress and clinical importance on pharmacogenetics in cancer therapy
- Author
-
Federico Innocenti, Wei Peng Yong, and Thomas I Peng Soh
- Subjects
medicine.medical_specialty ,business.industry ,Biochemistry (medical) ,Clinical Biochemistry ,Cancer therapy ,Antineoplastic Agents ,General Medicine ,Pharmacology ,Prognosis ,Article ,Pharmacogenetics ,Predictive Value of Tests ,Neoplasms ,Biomarkers, Tumor ,Medicine ,Marker Discovery ,Humans ,Personalized medicine ,Dosing ,business ,Intensive care medicine ,Severe toxicity - Abstract
Recent advances have provided unprecedented opportunities to identify prognostic and predictive markers of efficacy of cancer therapy. Genetic markers can be used to exclude patients who will not benefit from therapy, exclude patients at high risk of severe toxicity, and adjust dosing. Genomic approaches for marker discovery now include genome-wide association studies and tumor DNA sequencing. The challenge is now to select markers for which there is enough evidence to transition them to the clinic. The hurdles include the inherent low frequency of many of these markers, the lengthy validation process through trials, as well as legislative and economic hurdles. Attempts to answer questions about certain markers more quickly have led to an increased popularity of trials with enrichment design, especially in the light of the dramatic phase I results seen in recent months. Personalized medicine in oncology is a step closer to reality.
- Published
- 2011
19. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy
- Author
-
Sun Young Rha, Alex Boussioutas, Sze Huey Tan, Chia Huey Ooi, Akira Tsuburaya, Jaffer A. Ajani, Heike Grabsch, Niantao Deng, Wei Peng Yong, Sung Hoon Noh, Julian Lee, Khay Guan Yeoh, Patrick Tan, Ju Seog Lee, Ming Hui Lee, Jeanie Wu, Jimmy Bok Yan So, Tatiana Ivanova, Steven G. Rozen, Jae Ho Cheong, Han Chong Toh, Wai-Keong Wong, Wei Kiat Wan, Kiat Hon Lim, Iain Beehuat Tan, Manuel Salto Tellez, and Chee Wee Ong
- Subjects
Adult ,Male ,Organoplatinum Compounds ,Galectin 4 ,Kaplan-Meier Estimate ,Biology ,Bioinformatics ,medicine.disease_cause ,Article ,Young Adult ,Stomach Neoplasms ,medicine ,Biomarkers, Tumor ,Humans ,Survival rate ,Aged ,Proportional Hazards Models ,Cisplatin ,Aged, 80 and over ,Tissue microarray ,Hepatology ,Gene Expression Profiling ,Gastroenterology ,Cancer ,Middle Aged ,medicine.disease ,Cadherins ,Microarray Analysis ,Prognosis ,Oxaliplatin ,Gene expression profiling ,Survival Rate ,Cancer research ,Adenocarcinoma ,Female ,Fluorouracil ,Carcinogenesis ,medicine.drug - Abstract
Background & Aims Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large panel of GC cell lines. We tested if these subtypes might be associated with differences in patient survival times and responses to various standard-of-care cytotoxic drugs. Methods We analyzed gene expression profiles for 37 GC cell lines to identify intrinsic GC subtypes. These subtypes were validated in primary tumors from 521 patients in 4 independent cohorts, where the subtypes were determined by either expression profiling or subtype-specific immunohistochemical markers (LGALS4, CDH17). In vitro sensitivity to 3 chemotherapy drugs (5-fluorouracil, cisplatin, oxaliplatin) was also assessed. Results Unsupervised cell line analysis identified 2 major intrinsic genomic subtypes (G-INT and G-DIF) that had distinct patterns of gene expression. The intrinsic subtypes, but not subtypes based on Lauren's histopathologic classification, were prognostic of survival, based on univariate and multivariate analysis in multiple patient cohorts. The G-INT cell lines were significantly more sensitive to 5-fluorouracil and oxaliplatin, but more resistant to cisplatin, than the G-DIF cell lines. In patients, intrinsic subtypes were associated with survival time following adjuvant, 5-fluorouracil–based therapy. Conclusions Intrinsic subtypes of GC, based on distinct patterns of expression, are associated with patient survival and response to chemotherapy. Classification of GC based on intrinsic subtypes might be used to determine prognosis and customize therapy.
- Published
- 2010
20. A Predictive Study of the Dynamic Development of the P-Wave Terminal Force in Lead V1 in the Electrocardiogram in Relation to Long-Term Prognosis in Non-ST-Segment Elevation Acute Coronary Syndrome Patients during Hospitalization.
- Author
-
Li, Qiao, Gu, Li‐Dan, Zhang, Chen, Liu, Wei, Peng, Yong, Chai, Hua, Xu, Yuan‐Ning, Wei, Jia‐Fu, Chen, Mao, Huang, De‐Jia, Gu, Li-Dan, Xu, Yuan-Ning, Wei, Jia-Fu, and Huang, De-Jia
- Subjects
CARDIOVASCULAR disease diagnosis ,ACUTE coronary syndrome ,ELECTROCARDIOGRAPHY ,HOSPITAL care ,LONGITUDINAL method ,PROGNOSIS ,DIAGNOSIS - Abstract
Background: Changes in the ECG indicator PtfV1 reflect left atrial pressure and left ventricular diastolic function in NSTE-ACS patients during hospitalization. The value of PtfV1 in the evaluation of long-term prognosis in NSTE-ACS is still not clear. The purpose of this study was to investigate the relationship between the dynamic changes in P-wave terminal force in lead V1(PtfV1) in the ECG of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients during hospitalization and the long-term major adverse cardiovascular events (MACEs) of patients.Methods: A total of 595 patients who received coronary angiography and were confirmed as NSTE-ACS in the coronary heart disease database of Department of Cardiology of West China Hospital were continuously included. The PtfV1 and other clinical data at admission and discharge were collected and dynamically observed. The end events of follow-up observation were MACEs.Results: Follow-up was performed on 595 patients for 24.71 ± 1.95 months. There were 127 PtfV1(+) and 468 PtfV1(-) at admission, and the incidences of MACEs were 14.2% and 11.1%, respectively (P = 0.731). Compared with patients with persistent PtfV1(-) ECG at admission and discharge, 53 patients with persistent PtfV1(+) ECG at admission and discharge had increased risk for MACEs (HR: 2.221, 95% CI: 1.072-4.601, P = 0.032); 94 patients with new PtfV1(+) ECG at discharge also had significantly increased risk for MACEs (HR: 2.993, 95% CI: 1.660-5.397, P = 0.000).Conclusions: NSTE-ACS patients with persistent PtfV1(+) ECG indicators at admission and discharge and new PtfV1(+) at discharge had significantly increased risk of MACEs. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
21. Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas.
- Author
-
Wang, Ming, Jia, Jiaoying, Cui, Yan, Peng, Yong, and Jiang, Yugang
- Subjects
REGULATORY T cells ,PROGNOSIS ,IMMUNE checkpoint proteins ,TUMOR markers ,BRAIN tumors ,DRUG target - Abstract
Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. Methods: the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. Results: GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. Conclusions: these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
22. Novel SNP improves differential survivability and mortality in non-small cell lung cancer patients
- Author
-
Tzia Liang Mah, Ross A. Soo, Joo Chuan Tong, Frank Eisenhaber, Li Nanpu, Wei Peng Yong, Natalia Liem, Srinath Sridharan, Xin Ning Adeline Yap, Vellaisemy Kuralmani, Sharmila Adhikari, Sebastian Maurer-Stroh, Vachiranee Limviphuvadh, and Mengling Feng
- Subjects
Adult ,Male ,Models, Molecular ,dbSNP ,Lung Neoplasms ,Genotype ,Protein Conformation ,Active Transport, Cell Nucleus ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Survival Outcome ,Deoxycytidine ,Polymorphism, Single Nucleotide ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,medicine ,Biomarkers, Tumor ,Genetics ,SNP ,Humans ,Mortality ,Lung cancer ,Genetic variant ,Survival analysis ,Aged ,Cell Nucleus ,Research ,Computational Biology ,Biomarker ,Middle Aged ,medicine.disease ,DNA Polymerase I ,Prognosis ,Survival Analysis ,Gemcitabine ,Cancer cell ,Mutation ,Cancer research ,Female ,medicine.drug ,Biotechnology - Abstract
Background Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide due to poor patient prognosis and clinical outcome. Here, we studied the genetic variations underlying NSCLC pathogenesis based on their association to patient outcome after gemcitabine therapy. Results Bioinformatics analysis was used to investigate possible effects of POLA2 G583R (POLA2+1747 GG/GA, dbSNP ID: rs487989) in terms of protein function. Using biostatistics, POLA2+1747 GG/GA (rs487989, POLA2 G583R) was identified as strongly associated with mortality rate and survival time among NSCLC patients. It was also shown that POLA2+1747 GG/GA is functionally significant for protein localization via green fluorescent protein (GFP)-tagging and confocal laser scanning microscopy analysis. The single nucleotide polymorphism (SNP) causes DNA polymerase alpha subunit B to localize in the cytoplasm instead of the nucleus. This inhibits DNA replication in cancer cells and confers a protective effect in individuals with this SNP. Conclusions The results suggest that POLA2+1747 GG/GA may be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis.
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.