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EGFR Mutation in Nasopharyngeal Carcinoma. JOURNAL OF MOLECULAR PATHOLOGY 2022. [DOI: 10.3390/jmp3040017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Nasopharyngeal carcinoma is a malignant tumor of the nasopharynx. However, while radiotherapy is the primary choice of treatment, the treatment may fail due to distant metastasis in most patients at an advanced stage. Treatment agents against some mutations have led to the development of personalized treatment regimens. EGFR is one of the most studied molecules and has played a role in the development of a large number of cancer types. We aimed to demonstrate the EGFR mutation status in nasopharyngeal carcinomas. Twenty-six nasopharyngeal carcinomas were included in the study. EGFR mutation analysis was applied to the cases by the real-time PCR method. The results were evaluated statistically. No EGFR mutation was detected in any of the cases. Although EGFR expression is frequently shown in nasopharyngeal carcinomas immunohistochemically, the same positivity was not shown in genetic analysis. This result shows that the use of anti-EGFR agents in nasopharyngeal carcinoma treatment will not be effective.
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Han B, Fang T, Wang Y, Zhang Y, Xue Y. TGFβ2 is a Prognostic Biomarker for Gastric Cancer and is Associated With Methylation and Immunotherapy Responses. Front Genet 2022; 13:808041. [PMID: 35620459 PMCID: PMC9127534 DOI: 10.3389/fgene.2022.808041] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 04/25/2022] [Indexed: 12/24/2022] Open
Abstract
TGFβ signaling plays a key role in cancer progression and by shaping tumor architecture and inhibiting the anti-tumor activity of immune cells. It was reported that high expression of TGFβ can promote the invasion and metastasis of cancer cells in a variety of tumors. However, there are few studies on TGFβ2 and its methylation in gastric cancer. We analyzed the Harbin Medical University Cancer Hospital (HMUCH) sequencing data and used public data to explore the potential function and prognostic value of TGFβ2 and its methylation in gastric cancer. In this study, we used the ssGSEA algorithm to quantify 23 methylation sites related to TGFβ2. Survival analysis showed that high expression of TGFβ2 and hypomethylation levels of TGFβ2 were negative factors in the prognosis of gastric cancer. Functional enrichment analysis of methylation revealed that methylation of different TGFβ2 methylation scores was mainly involved in energy metabolism, extracellular matrix formation and cell cycle regulation. In the gastric cancer microenvironment TGFβ2 was associated with high levels of multiple immune cell infiltration and cytokine expression, and high TGFβ2 expression was significantly and positively correlated with stemness markers, stromalscore and EMT. Gene set enrichment analysis also revealed an important role of TGFβ2 in promoting EMT. In addition, we discussed the relationship between TGFβ2 and immunotherapy. The expression of PD-1, PD-L1 and CTLA-4 was elevated in the TGFβ2 high expression group. Also when TGFβ2 was highly expressed, the responsiveness of immune checkpoint blockade (ICB) was significantly enhanced. This indicates that TGFβ2 may become an indicator for predicting the efficacy of immunosuppressive agents and a potential target for immunotherapy.
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Affiliation(s)
- Bangling Han
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Tianyi Fang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yimin Wang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yongle Zhang
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yingwei Xue
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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Identification of Novel Gene Signature Associated with Cell Glycolysis to Predict Survival in Hepatocellular Carcinoma Patients. JOURNAL OF ONCOLOGY 2021; 2021:5564525. [PMID: 34035809 PMCID: PMC8118732 DOI: 10.1155/2021/5564525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/22/2021] [Indexed: 01/27/2023]
Abstract
Purpose As hepatocellular carcinoma (HCC) is a complex disease, it is hard to classify HCC with a specific biomarker. This study used data from TCGA to create a genetic signature for predicting the prognosis of HCC patients. Methods In a group of HCC patients (n = 424) from TCGA, mRNA profiling was carried out. To recognize gene sets that differed significantly between HCC and normal tissues, an enrichment study of genes was carried out. Cox relative hazard regression models have been used to identify genes that are significantly associated with overall survival. To test the function of a prognostic risk parameter, the following multivariate Cox regression analysis was used. The log-rank test and Kaplan–Meier survival estimates were used to test the significance of risk parameters for predictive prognoses. Results Eight genes have been identified as having a significant link to overall survival (PAM, NUP155, GOT2, KDELR3, PKM, NSDHL, ENO1, and SRD5A3). The 377 HCC patients were divided into eight-gene signature-based high/low-risk subgroups. The eight-gene signature's prognostic ability was unaffected by a number of factors. Conclusion To predict the survival of patients with HCC, an eight-gene signature associated with cellular glycolysis was then identified. The findings shed light on cellular glycolysis processes and the diagnosis of patients with low HCC prognoses.
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Zhu K, Zhan H, Peng Y, Yang L, Gao Q, Jia H, Dai Z, Tang Z, Fan J, Zhou J. Plasma hsa_circ_0027089 is a diagnostic biomarker for hepatitis B virus-related hepatocellular carcinoma. Carcinogenesis 2020; 41:296-302. [PMID: 31535687 PMCID: PMC7221502 DOI: 10.1093/carcin/bgz154] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Revised: 08/10/2019] [Accepted: 09/12/2019] [Indexed: 12/11/2022] Open
Abstract
Circular RNAs (circRNAs) have recently been identified as a new member of endogenous noncoding RNAs. CircRNAs exhibit high stability and can thus can be used as valuable biomarkers for monitoring the occurrence and development of hepatocellular carcinoma (HCC). The present study sought to explore the diagnostic significance of plasma circRNAs in hepatitis B virus (HBV)-related HCC. Plasma circRNAs from 10 patients with hepatitis B (HBV)-related HCC and 5 patients with HBV-related liver cirrhosis were investigated by microarray to screen differentially expressed circRNAs, 157 upregulated and 161 downregulated circRNAs were found. Twenty-four circRNAs were further investigated via quantitative reverse-transcriptase–polymerase chain reaction assay in a training cohort (n = 48), hsa_circ_0027089 exhibited the highest significance and further distinguished 64 HCC patients from 40 cirrhosis patients and 72 healthy participants in a validation cohort. These results indicate that plasma hsa_circ_0027089 can serve as a new marker for the diagnosis of HBV-related HCC.
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Affiliation(s)
- Kai Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Key Laboratory of Medical Epigenetics and Metabolism, Institute of Biomedical Sciences, Fudan University, Shanghai, China
| | - Hao Zhan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Yuanfei Peng
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Liuxiao Yang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Hao Jia
- Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Zhi Dai
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Zhaoyou Tang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Key Laboratory of Medical Epigenetics and Metabolism, Institute of Biomedical Sciences, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratorsy of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.,Key Laboratory of Medical Epigenetics and Metabolism, Institute of Biomedical Sciences, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Organ Transplantation, Shanghai, China
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Singh AK, Kumar R, Pandey AK. Hepatocellular Carcinoma: Causes, Mechanism of Progression and Biomarkers. Curr Chem Genom Transl Med 2018; 12:9-26. [PMID: 30069430 PMCID: PMC6047212 DOI: 10.2174/2213988501812010009] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 05/15/2018] [Accepted: 05/20/2018] [Indexed: 01/18/2023] Open
Abstract
Hepatocellular Carcinoma (HCC) is one of the most common malignant tumours in the world. It is a heterogeneous group of a tumour that vary in risk factor and genetic and epigenetic alteration event. Mortality due to HCC in last fifteen years has increased. Multiple factors including viruses, chemicals, and inborn and acquired metabolic diseases are responsible for its development. HCC is closely associated with hepatitis B virus, and at least in some regions of the world with hepatitis C virus. Liver injury caused by viral factor affects many cellular processes such as cell signalling, apoptosis, transcription, DNA repair which in turn induce important effects on cell survival, growth, transformation and maintenance. Molecular mechanisms of hepatocellular carcinogenesis may vary depending on different factors and this is probably why a large set of mechanisms have been associated with these tumours. Various biomarkers including α-fetoprotein, des-γ-carboxyprothrombin, glypican-3, golgi protein-73, squamous cell carcinoma antigen, circulating miRNAs and altered DNA methylation pattern have shown diagnostic significance. This review article covers up key molecular pathway alterations, biomarkers for diagnosis of HCC, anti-HCC drugs and relevance of key molecule/pathway/receptor as a drug target.
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Affiliation(s)
| | | | - Abhay K. Pandey
- Department of Biochemistry, University of Allahabad, Allahabad 211002, India
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Genes directly regulated by NF-κB in human hepatocellular carcinoma HepG2. Int J Biochem Cell Biol 2017; 89:157-170. [PMID: 28579529 DOI: 10.1016/j.biocel.2017.05.031] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 05/25/2017] [Accepted: 05/29/2017] [Indexed: 12/14/2022]
Abstract
It has been well-known that over activation of NF-κB has close relationship with hepatitis and hepatocellular carcinoma (HCC). However, the complete and exact underlying molecular pathways and mechanisms still remain not fully understood. By manipulating NF-κB activity with its recognized activator TNFα and using ChIP-seq and RNA-seq techniques, this study identified 699 NF-κB direct target genes (DTGs) in a widely used HCC cell line, HepG2, including 399 activated and 300 repressed genes. In these NF-κB DTGs, 216 genes (126 activated and 90 repressed genes) are among the current HCC gene signature. In comparison with NF-κB target genes identified in LPS-induced THP-1 and TNFα-induced HeLa cells, only limited numbers (24-46) of genes were shared by the two cell lines, indicating the HCC specificity of identified genes. Functional annotation revealed that NF-κB DTGs in HepG2 cell are mainly related with many typical NF-κB-related biological processes including immune system process, response to stress, response to stimulus, defense response, and cell death, and signaling pathways of MAPK, TNF, TGF-beta, Chemokine, NF-kappa B, and Toll-like receptor. Some NF-κB DTGs are also involved in Hepatitis C and B pathways. It was found that 82 NF-κB DTGs code secretory proteins, which include CCL2 and DKK1 that have already been used as HCC markers. Finally, the NF-κB DTGs were further confirmed by detecting the NF-κB binding and expression of 14 genes with ChIP-PCR and RT-PCR. This study thus provides a useful NF-κB DTG list for future studies of NF-κB-related molecular mechanisms and theranostic biomarkers of HCC.
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Ezzat WM, Amr KS. Insights for hepatitis C virus related hepatocellular carcinoma genetic biomarkers: Early diagnosis and therapeutic intervention. World J Hepatol 2016; 8:1251-1261. [PMID: 27843535 PMCID: PMC5084054 DOI: 10.4254/wjh.v8.i30.1251] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 07/15/2016] [Accepted: 09/08/2016] [Indexed: 02/06/2023] Open
Abstract
The current review explores the role of emerging molecular contributing factors in liver carcinogenesis on top of hepatitis C virus (HCV). Here we will try to discuss the role genetic and epigenetic factors in pathogenesis of hepatocellular carcinoma. Understanding the role of these factors will help in discovering the mystery of liver carcinogenesis on top of chronic HCV infection. Moreover, use of the studied molecular factors will provide the hepatologists with tailored diagnostic promising biomarkers and flatten the way for establishment of emerging molecular treatment based on exploring the molecular subscription of this aggressive liver cancer.
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Zhang JW, Qin T, Hong SD, Zhang J, Fang WF, Zhao YY, Yang YP, Xue C, Huang Y, Zhao HY, Ma YX, Hu ZH, Huang PY, Zhang L. Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma. CHINESE JOURNAL OF CANCER 2015; 34:177-83. [PMID: 25963410 PMCID: PMC4593383 DOI: 10.1186/s40880-015-0011-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 02/09/2015] [Indexed: 01/13/2023]
Abstract
INTRODUCTION An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. METHODS By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. RESULTS Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. CONCLUSIONS Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.
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Affiliation(s)
- Jian-Wei Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Tao Qin
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Shao-Dong Hong
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Jing Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Wen-Feng Fang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Yuan-Yuan Zhao
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Yun-Peng Yang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Cong Xue
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Yan Huang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Hong-Yuan Zhao
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Yu-Xiang Ma
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Zhi-Huang Hu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| | - Pei-Yu Huang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
| | - Li Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
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Yin J, Hou P, Wu Z, Wang T, Nie Y. Circulating miR-375 and miR-199a-3p as potential biomarkers for the diagnosis of hepatocellular carcinoma. Tumour Biol 2015; 36:4501-7. [PMID: 25618599 DOI: 10.1007/s13277-015-3092-0] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 01/08/2015] [Indexed: 12/26/2022] Open
Abstract
Aiming to find novel non-invasive biomarkers with high accuracy for the detention of early-stage hepatocellular carcinoma (HCC), we examined the predictive power of two microRNAs (miR; miR-375 and miR-199a-3p) as potential biomarkers in early-stage HCC. A total of 234 serum samples (78 samples from HCC patients, 156 samples from healthy controls) were collected. We measured the levels of the two mature microRNAs (miRNAs) (miR-375 and miR-199a-3p) with probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in all subjects. In addition, the correlation between the expression levels of two miRs and clinicopathological factors was explored. Receiver operating characteristic curve (ROC) analyses revealed that the two serum miRs could be promising biomarkers for HCC, with relatively high area under the curve (AUC) values as follows: miR-375, 0. 637 with 95 % confidence interval (CI) of 0.560-0.741; miR-199a-3p, 0. 883 with 95 % CI of 0.827-0.938. Stratified analyses indicated that circulating miR-199a-3p showed better predictive value in patients with long-term drinking. Our data suggested that circulating miR-375 and miR-199a-3p could be a novel serum biomarker for HCC. Nevertheless, further validating and improving study with larger sample should be conducted to confirm our results.
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Affiliation(s)
- Jian Yin
- Department of Gastroenterology, The First Affiliated to Chinese PLA General Hospital, 51 Fucheng Road, Beijing, 100048, China,
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10
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Liu AM, Wang W, Luk JM. miRNAs: new tools for molecular classification, diagnosis and prognosis of hepatocellular carcinoma. Hepat Oncol 2014; 1:323-329. [PMID: 30190966 DOI: 10.2217/hep.14.9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide, ranking as the third leading cause of cancer-related death. With recent advances in understanding HCC biology, progress has been made in early detection and management of HCC; however, its prognosis remains dismal. Novel biomarkers for HCC that are acceptable for clinical utility are urgently in need. Recently, miRNA has emerged as an important class of gene regulator that controls various cellular processes including cancer development. In HCC, miRNAs are frequently dysregulated, and studies have shown great promises of miRNAs as biomarkers for tumor classification, diagnosis and prognosis. Given miRNAs are highly stable in blood plasma and serum, they are suggested as a new class of noninvasive biomarker for detection of HCC. In this article, we provide an up-to-date review of the recent findings of the use of miRNAs in molecular classification of HCC tumors, diagnosis and prognosis.
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Affiliation(s)
- Angela M Liu
- Department of Pharmacology, National University of Singapore, Singapore.,Department of Pharmacology, National University of Singapore, Singapore
| | - Wei Wang
- Department of Pharmacology, National University of Singapore, Singapore.,Department of Pharmacology, National University of Singapore, Singapore
| | - John M Luk
- Department of Pharmacology, National University of Singapore, Singapore.,Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,Department of Pharmacology, National University of Singapore, Singapore.,Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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Zhao H, Li Y, Wang S, Yang Y, Wang J, Ruan X, Yang Y, Cai K, Zhang B, Cui P, Yan J, Zhao Y, Wakeland EK, Li Q, Hu S, Fang X. Whole transcriptome RNA-seq analysis: tumorigenesis and metastasis of melanoma. Gene 2014; 548:234-43. [PMID: 25034661 DOI: 10.1016/j.gene.2014.07.038] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 06/27/2014] [Accepted: 07/12/2014] [Indexed: 12/31/2022]
Abstract
Melanoma is the most malignant cutaneous cancer and causes over 9000 deaths annually. Because fatality rates from malignant melanoma (MM) increase dramatically upon metastasis, we investigated tumorigenesis and metastasis of MM in transcriptome analyses of three distinct cell lines that correspond with the stages of MM pathogenesis: the normal stage (HEMn-LP), the onset of MM (A375), and the metastasis stage (A2058). Using next-generation sequencing (NGS) technology, we detected asymmetrical expression of genes among the three cell lines, notably on chromosomes 9, 11, 12, and 14, suggesting their involvement in tumorigenesis and metastasis of MM. These genes were clustered into 41 categories based on their expression patterns, and their biological functions were analyzed using Ingenuity Pathway Analysis. In the top cancer-associated category, HIF1A, IL8, TERT, ONECUT1, and FOXA1 directly interacted with either transcription factors or cytokines that are known to be involved in the tumorigenesis or metastasis of other malignant tumors. The present data suggest that cytokine regulatory pathways in macrophages predominate over other pathways during the pathogenesis of MM. This study provides new targets for the downstream mechanistic studies of the tumorigenesis and metastasis of MM and demonstrates a new strategy for studies of the progression of other malignant cancers.
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Affiliation(s)
- Hua Zhao
- Department of Dermatology, General Hospital of People's Liberation Army, Beijing 100853, China
| | - Yongjun Li
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Shaobin Wang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Yadong Yang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Junyun Wang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Xiuyan Ruan
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Yaran Yang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Kan Cai
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Bing Zhang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Peng Cui
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Jiangwei Yan
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Yongliang Zhao
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Edward K Wakeland
- Department of Immunology & Microarray Core Facility, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
| | - Quanzhen Li
- Department of Immunology & Microarray Core Facility, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
| | - Songnian Hu
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
| | - Xiangdong Fang
- CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
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Wu K, House L, Liu W, Cho WC, 南 娟. [Personalized targeted therapy for lung cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2013; 16:C21-C34. [PMID: 23945250 PMCID: PMC6123569 DOI: 10.3779/j.issn.1009-3419.2013.08.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
由于每一肺癌患者在临床特征、预后、治疗反应和耐受性方面的进展都是独特的，所以肺癌被认为是异质性疾病。个体化用药是指运用标志物来预测哪些患者更易获益于某种治疗。对于肺癌而言，日趋完善的表皮生长因子受体(epidermal growth factor receptor, EGFR)和新发现的棘皮动物微管相关蛋白样4-间变淋巴瘤激酶(echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase, EML4-ALK)是重要的治疗靶标。本综述包括EGFR和EML4-ALK活化的机制、预测性生物标记物、耐药的机理和已有的靶向性酪氨酸激酶抑制剂。本文将通过总结基于生物标记物筛选患者而进行的前瞻性临床试验来探讨EGFR和ALK靶向治疗的疗效。此外，由于革命性的测序和系统生物学技术会为癌症的分子特征提供一个全面的理解，有助于为更适宜靶向治疗的患者提供更精确的区分从而提供更有前景的个体化治疗，本综述也将包括这些技术。同时，非亚裔人群中EGFR和ALK相对较低的突变发生率和突变患者反应的缺乏限制了靶向于EGFR或ALK的治疗的应用。测序和系统生物学策略则可能为这些患者提供新的解决方案。
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Affiliation(s)
- Kehua Wu
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Larry House
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Wanqing Liu
- Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayete, IN 47907, USA
| | - William C.S. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
| | - 娟 南
- 天津医科大学总医院，天津市肺癌研究所，天津市肺癌转移与肿瘤微环境重点实验室
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Prow TW, Lin LL, Soyer HP. The opportunity for microbiopsies for skin cancer. Future Oncol 2013; 9:1241-3. [PMID: 23654202 DOI: 10.2217/fon.13.88] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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Zhu K, Dai Z, Zhou J. Biomarkers for hepatocellular carcinoma: progression in early diagnosis, prognosis, and personalized therapy. Biomark Res 2013; 1:10. [PMID: 24252133 PMCID: PMC4177612 DOI: 10.1186/2050-7771-1-10] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2012] [Accepted: 02/02/2013] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Currently, surgical resection, liver transplantation, and local ablation are considered curative therapeutic practices for HCC. The diagnosis of HCC without pathologic confirmation is achieved by analyzing serum alpha-fetoprotein (AFP) levels combined with imaging techniques, including ultrasonography, magnetic resonance imaging, and computerized tomography. Although progress has been made in the diagnosis and management of HCC, its prognosis remains dismal. Various new technologies have identified numerous novel biomarkers with potential diagnostic as well as prognostic value, including Dickkopf-1 and Golgi protein 73. These biomarkers not only help in the early diagnosis and prediction of prognosis, but also assist in identifying potential targets for therapeutic interventions. In this article, we provide an up-to-date review of the biomarkers that are used for early diagnosis, prognosis prediction, and personalized treatment of HCC.
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Affiliation(s)
- Kai Zhu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, 200032, China
| | - Zhi Dai
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, 200032, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai, 200032, China
- Shanghai Key Laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
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Wu K, House L, Liu W, Cho WC. Personalized targeted therapy for lung cancer. Int J Mol Sci 2012; 13:11471-11496. [PMID: 23109866 PMCID: PMC3472758 DOI: 10.3390/ijms130911471] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Revised: 09/05/2012] [Accepted: 09/07/2012] [Indexed: 01/06/2023] Open
Abstract
Lung cancer has long been recognized as an extremely heterogeneous disease, since its development is unique in every patient in terms of clinical characterizations, prognosis, response and tolerance to treatment. Personalized medicine refers to the use of markers to predict which patient will most likely benefit from a treatment. In lung cancer, the well-developed epidermal growth factor receptor (EGFR) and the newly emerging EML4-anaplastic lymphoma kinase (ALK) are important therapeutic targets. This review covers the basic mechanism of EGFR and EML4-ALK activation, the predictive biomarkers, the mechanism of resistance, and the current targeted tyrosine kinase inhibitors. The efficacy of EGFR and ALK targeted therapies will be discussed in this review by summarizing the prospective clinical trials, which were performed in biomarker-based selected patients. In addition, the revolutionary sequencing and systems strategies will also be included in this review since these technologies will provide a comprehensive understanding in the molecular characterization of cancer, allow better stratification of patients for the most appropriate targeted therapies, eventually resulting in a more promising personalized treatment. The relatively low incidence of EGFR and ALK in non-Asian patients and the lack of response in mutant patients limit the application of the therapies targeting EGFR or ALK. Nevertheless, it is foreseeable that the sequencing and systems strategies may offer a solution for those patients.
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Affiliation(s)
- Kehua Wu
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA; E-Mails: (K.W.); (L.H.)
| | - Larry House
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA; E-Mails: (K.W.); (L.H.)
| | - Wanqing Liu
- Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA; E-Mail:
| | - William C.S. Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
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