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Cheng T, Chen J, Ying P, Wei H, Shu H, Kang M, Zou J, Ling Q, Liao X, Wang Y, Shao Y. Clinical risk factors of carbohydrate antigen-125, cytokeratin fragment 19, and neuron-specific enolase in liver metastases from elderly lung cancer patients. Front Genet 2022; 13:1013253. [PMID: 36246602 PMCID: PMC9557119 DOI: 10.3389/fgene.2022.1013253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 09/12/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: Lung cancer is a common malignant tumor characterized by challenging detection and lack of specificity in clinical manifestations. To investigate the correlation of tumor markers in the serum with liver metastasis and prognosis of lung cancer.Methods: A total of 3,046 elderly lung cancer patients were retrospectively studied between September 1999 and July 2020. Divided into liver metastasis group and non-liver metastasis group. We compared a series of serum biomarkers between the two groups of elderly patients to predict the prognosis in patients with lung cancer by fluorescence in situ hybridization (FISH), advanced flow cytometry (FCM) and multi tumor marker protein chip, including tumor markers in the serum included alkaline phosphatase (ALP), serum calcium, hemoglobin (HB), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin fragment 19 (Cyfra21-1), carbohydrate antigen-125 (CA-125), carbohydrate antigen-153 (CA-153), carbohydrate antigen-199 (CA-199), and free prostate specific antigen (free PSA). We used binary logistic regression analysis to determine risk factors, and used receiver operating curve (ROC) analysis to evaluate the diagnostic value of liver metastases in elderly patients with lung cancer.Results: The proportion of lung cancer in the liver metastasis group was higher than that observed in the non-liver metastases group. The expression levels of CA-125, Cyfra21-1, and NSE in the liver metastasis group of lung cancer were significantly higher than those reported in the non-liver metastases group (p < 0.05). ROC curve analysis shows that the area under the curve of CA-125, Cyfra21-1, and NSE are 0.614, 0.616 and 0.608, respectively. The sensitivity and specificity of CA-125 were 45.70% and 76.20%, the sensitivity and specificity of Cyfra21-1 were 60.10% and 57.10%, and the sensitivity and specificity of NSE were 44.10% and 75.00%, respectively.Conclusion: High levels of CA-125, Cyfra21-1, and NSE in the serum may be associated with liver metastasis in elderly patients with lung cancer. CA-125 and NSE are factors influencing the prognosis of elderly patients with liver metastasis of lung cancer.
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Affiliation(s)
- Tao Cheng
- Department of Respiratory, Shangrao People’s Hospital of Nanchang University, Shangrao, Jiangxi, China
| | - Jun Chen
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ping Ying
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Hong Wei
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Huiye Shu
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Min Kang
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jie Zou
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Qian Ling
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xulin Liao
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Yixin Wang
- School of Optometry and Vision Science, Cardiff University, Cardiff, United Kingdom
| | - Yi Shao
- Department of Ophthalmology, Jiangxi Branch of National Clinical Research Center for Ocular Disease, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- *Correspondence: Yi Shao,
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mTOR up-regulation of SNRPA1 contributes to hepatocellular carcinoma development. Biosci Rep 2021; 40:224382. [PMID: 32420585 PMCID: PMC7295620 DOI: 10.1042/bsr20193815] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 05/05/2020] [Accepted: 05/14/2020] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Recent studies showed that snRNPs were implicated in human cancer development. The role of SNRPA1, which is a member of U2 snRNPs, in HCC, remains undocumented. Here, we found that SNRPA1 was highly expressed in HCC tissue compared with normal adjacent liver tissues. Up-regulation of SNRPA1 was correlated with the clinical stage of HCC and the overall survival of HCC patients. In vitro and in vivo results showed that knockdown of SNPRA1 inhibited the cell proliferation, colony formation and xenografted tumorigenesis of HCC cells. Apoptosis was induced by SNPRA1 down-regulation. Mechanistically, SNPRA1 was stimulated by mTOR activation. In addition, whole-genome microarray analysis identified that 262 genes were up-regulated and 462 genes were down-regulated by SNPRA1 knockdown in HCC cells. qPCR analysis suggested that the fibroblast growth factor-2 (FGF2), Alpha-fetoprotein (AFP), β-catenin, Ki-67 and cyclin B1 were down-regulated and caspase 3, p53 as well as p21 were up-regulated after SNRPA1 knockdown. Taken together, our findings implicate that SNPRA1 functions as an oncogene in HCC.
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Zhang Y, Xi Y, Fang J, Luo S, Wilson JJ, Huang RP. Identification and characterization of monoclonal antibodies against GP73 for use as a potential biomarker in liver cancer screening and diagnosis. J Immunoassay Immunochem 2016; 37:390-406. [PMID: 27088654 DOI: 10.1080/15321819.2016.1154866] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Golgi membrane protein 1, or GP73, is recently being evaluated as a novel cancer biomarker against prostate cancer, lung adenocarcinoma, and hepatocellular carcinoma (HCC). In the microenvironment of HCC, GP73 expression levels are significantly elevated. It is this elevation that may prove more specific and sensitive for HCC detection than that of the traditional biomarker, alpha-fetoprotein (AFP). This may be especially true if it can be measured and identified earlier in the diagnostic process. We sought to develop a testing platform to measure GP73 levels for the purposes of earlier diagnostic screening of at risk patients. We expressed recombinant GP73 protein to use as an immunogen in order to develop several monoclonal anti-GP73 antibodies. Three clones, 1D7, 2B2, and 5B4, were identified with all three having a higher than 1:5,000,000 titer. These clones were then isotyped and validated to bind the immunogen protein. Different combinations of antibody pairs were then tested in order to create a functional sandwich antibody pair. Using this pair on liver disease patient serum samples, we found that GP73 was significantly elevated when compared to healthy control patient serum (P < 0.0001). Average GP73 levels in HCC patients was 284.0 ng/mL, slightly higher than liver disease patients (265.6 ng/mL), and significantly elevated over normal serum levels is (74.86 ng/mL). The area under the receiver-operating characteristic curve (ROC) for GP73 to detect liver cancer was 0.98 (95% CI, 0.95 to 1.00; P < 0.0001), and GP73 levels had a sensitivity of 97%, a specificity of 87% for detecting liver cancer. By contrast, the sensitivity and specificity of liver disease detection was 76% and 97%, respectively. We then tested detection of 74 serum samples (n control = 46, n liver disease = 7, n liver cancer = 21) by our ELISA testing methodology and commercial kit simultaneously. The results found that our kit and the commercial kit had a good linear correlation coefficient, r(2) = 0.932. Together these clones and our ELISA pair may prove extremely useful in the detection and monitoring of GP73 in HCC and other at risk patients.
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Affiliation(s)
- Yuming Zhang
- a Raybiotech, Inc ., Guangzhou , China.,c RayBiotech, Inc ., Norcross , Georgia , USA
| | - Yun Xi
- b The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Jianmin Fang
- a Raybiotech, Inc ., Guangzhou , China.,c RayBiotech, Inc ., Norcross , Georgia , USA.,d South China Biochip Research Center , Guangzhou , China
| | - Shuhong Luo
- a Raybiotech, Inc ., Guangzhou , China.,c RayBiotech, Inc ., Norcross , Georgia , USA.,d South China Biochip Research Center , Guangzhou , China
| | | | - Ruo-Pan Huang
- a Raybiotech, Inc ., Guangzhou , China.,c RayBiotech, Inc ., Norcross , Georgia , USA.,d South China Biochip Research Center , Guangzhou , China
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Shahat AA, Alsaid MS, Kotob SE, Ahmed HH. Significance of Rumex vesicarius as anticancer remedy against hepatocellular carcinoma: a proposal-based on experimental animal studies. Asian Pac J Cancer Prev 2016; 16:4303-10. [PMID: 26028090 DOI: 10.7314/apjcp.2015.16.10.4303] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Rumex vesicarius is an edible herb distributed in Egypt and Saudi Arabia. The whole plant has significant value in folk medicine and it has been used to alleviate several diseases. Hepatocellular carcinoma (HCC), the major primary malignant tumor of the liver, is one of the most life-threatening human cancers. The goal of the current study was to explore the potent role of Rumex vesicarius extract against HCC induced in rats. Thirty adult male albino rats were divided into 3 groups: (I): Healthy animals received orally 0.9% normal saline and served as negative control group, (II): HCC group in which rats were orally administered N-nitrosodiethylamine NDEA, (III): HCC group treated orally with R. vesicarius extract in a dose of 400 mg/kg b.wt daily for two months. ALT and AST, ALP and γ-GT activities were estimated. CEA, AFP, AFU, GPC-3, Gp-73 and VEGF levels were quantified. Histopathological examination of liver tissue sections was also carried out. The results of the current study showed that the treatment of the HCC group with R. vesicarius extract reversed the significant increase in liver enzymes activity, CEA, AFP, AFU, glypican 3, golgi 73 and VEGF levels in serum as compared to HCC-untreated counterparts. In addition, the favorable impact of R. vesicarius treatment was evidenced by the marked improvement in the histopathological features of the liver of the treated group. In conclusion, the present experimental setting provided evidence for the significance of R. vesicarius as anticancer candidate with a promising anticancer potential against HCC. The powerful hepatoprotective properties, the potent antiangiogenic activity and the effective antiproliferative capacity are responsible for the anticancer effect of this plant.
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Affiliation(s)
- Abdelaaty A Shahat
- Pharmacognosy Department, College of Pharmacy, King Saud University, Giza, Egypt E-mail :
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Liu WT, Lu X, Tang GH, Ren JJ, Liao WJ, Ge PL, Huang JF. LncRNAs expression signatures of hepatocellular carcinoma revealed by microarray. World J Gastroenterol 2014; 20:6314-6321. [PMID: 24876753 PMCID: PMC4033470 DOI: 10.3748/wjg.v20.i20.6314] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the expression profiles of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma.
METHODS: Hepatocellular carcinoma (HCC) tissues and matched adjacent non-tumor (NT) liver tissues were collected from 29 patients with HCC, immediately after liver resection, between March 2011 and July 2013. The diagnosis of HCC was made based on histological examination. Differentially expressed lncRNAs between HCC and NT tissues were revealed through microarray-based lncRNAs expression profiling. Further, quantification of selected lncRNAs was performed using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).
RESULTS: Six hundred and fifty-nine lncRNAs were differentially expressed between HCC and NT tissues, of which five [TCONS_00018278, AK093543, D16366, ENST00000501583, NR_002819 (MALAT1)] were selected for validation. Four of them were significantly downregulated in HCC tissues compared with NT tissues (P = 0.012, 0.045, 0.000 and 0.000, respectively), and the expression level of MALAT1 showed no significant difference (P = 0.114).
CONCLUSION: This study identified a set of lncRNAs differentially expressed in HCC tissues and provided useful information for exploring potential therapeutic targets and diagnostic biomarkers of this cancer.
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Evaluation of individual and combined applications of serum biomarkers for diagnosis of hepatocellular carcinoma: a meta-analysis. Int J Mol Sci 2013; 14:23559-80. [PMID: 24317431 PMCID: PMC3876063 DOI: 10.3390/ijms141223559] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 10/31/2013] [Accepted: 11/07/2013] [Indexed: 12/14/2022] Open
Abstract
The clinical value of Serum alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP) and Golgi protein-73 (GP73) have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC) was obtained. A meta-analysis was carried out in which the area under the curve (AUC) for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73) was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies.
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Shan SG, Gao YT, Xu YJ, Huang Y, Zhang Q, Zhai DK, Li JB, Wang FM, Jing X, Du Z, Wang YJ. Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients. Hepatol Res 2013; 43:1199-210. [PMID: 23607749 DOI: 10.1111/hepr.12078] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2012] [Revised: 01/16/2013] [Accepted: 01/20/2013] [Indexed: 12/23/2022]
Abstract
AIM Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters. METHODS Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay. RESULTS GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P < 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P < 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor-node-metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. CONCLUSION GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.
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Affiliation(s)
- Shi-Gang Shan
- Third Central Clinical College of Tianjin Medical University, Tianjin, China; Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China
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Hu JS, Wu DW, Liang S, Miao XY. GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population. Med Oncol 2009; 27:339-45. [PMID: 19399652 DOI: 10.1007/s12032-009-9215-y] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2009] [Accepted: 03/30/2009] [Indexed: 12/11/2022]
Abstract
Golgi protein-73 (GP73) is a newly identified candidate serum marker for HCC, but GP73 study now is lesser in Asian population. The aims of this study were to determine how GP73 is detected in the serum of healthy, hepatitis B, cirrhosis and HCC by western blotting and RT-PCR, and to establish the sensitivity and specificity of serum GP73 protein and RNA for diagnosing HCC. Serum GP73 was detected by western blotting and RT-PCR, and quantified by densitometric analysis. GP73 was measured in serum from 124 patients with various forms of liver. AFP was tested using commercially available electrochemiluminescence immunoassay. The median sGP73 in patients with HBV-related HCC was significantly higher (P < 0.001) than in healthy individuals and in patients with other diseases. When sGP73 protein was used to detect HBV-related HCC, it had a sensitivity of 77.4% and a specificity of 83.9%, at the optimal cut-off value of 7.4 relative units. The area under the receiver-operating characteristic curve was 0.89. GP73 RNA in patients with HBV-related HCC had a sensitivity of 87.1% and a specificity of 83.9% and AUROC of 0.92. AFP in patients with HCC had a sensitivity of 48.4% and a specificity of 96.8% and AUROC of 0.77. GP73 protein and RNA can be found in the serum of patients with HBV-related HCC obviously higher than of other liver diseases in Asian. GP73 was better than AFP for the diagnosis of HBV-related HCC. RT-PCR is a more sensitive and superior method of quantification than Western blot. Furthermore, our data need to be confirmed in larger cohorts of patients.
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Affiliation(s)
- Jin-song Hu
- Department of General Surgery, Xiangya Second Hospital, Xiangya Medical College, Central South University, Changsha, Hunan, China.
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