Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma

Gallbladder carcinoma (GBC) is a common malignancy and is usually diagnosed in the late stages of the disease. The identification of new effective early diagnostic biomarkers could represent an effective approach in reducing mortality in GBC. Altered expression of long non-coding RNAs (lncRNAs) is b...

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Main Authors: Sridhar Mishra, Pallavi Srivastava, Anshuman Pandey, Akash Agarwal, Saumya Shukla, Nuzhat Husain
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-06-01
Series:Non-coding RNA Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S246805402400026X
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author Sridhar Mishra
Pallavi Srivastava
Anshuman Pandey
Akash Agarwal
Saumya Shukla
Nuzhat Husain
author_facet Sridhar Mishra
Pallavi Srivastava
Anshuman Pandey
Akash Agarwal
Saumya Shukla
Nuzhat Husain
author_sort Sridhar Mishra
collection DOAJ
description Gallbladder carcinoma (GBC) is a common malignancy and is usually diagnosed in the late stages of the disease. The identification of new effective early diagnostic biomarkers could represent an effective approach in reducing mortality in GBC. Altered expression of long non-coding RNAs (lncRNAs) is believed to be associated with the emergence and development of GBC. Our study aims to identify the expression of a range of circulating lncRNAs, including HOTAIR, ANRIL, H19, CCAT1 and MEG3, in matched serum and tissues of GBC for diagnosis and its association with clinicopathological features. The case and control study included matched serum and tissues from 63 GBC, 19 cholecystitis (CC), and 46 normal controls (NC). RNA extraction and cDNA synthesis from serum and fresh tissue match were performed using commercially available kits. Relative expression was assessed using SYBR Green real-time quantitative polymerase chain reaction. Circulating lncRNA levels including HOTAIR, ANRIL and H19 were upregulated in serum samples, while MEG3 and CCAT1 were downregulated in GBC compared to controls. The trend towards upregulation and downregulation was comparable in the tissue. HOTAIR and MEG3 levels were significantly different between serum CC and early-stage GBC (p = 0.0373, 0.0020), while H19 was significantly upregulated comparing early-stage GBC to advanced-stage GBC (p = 0.018). The expression of ANRIL was significant with M stage (p = 0.0488), H19 with stage (p = 0.009), M stage (p=<0.0001) &amp; stage (0.009) and CCAT1 with M stage (0.044). When distinguishing GBC and NC, AUC for HOTAIR was 0.75, ANRIL 0.78, H19 0.74, CCAT1 0.80 and 0.96 for MEG3. The combination sensitivity for lncRNAs ranged from 84.13% (CI: 72.74–92.12%) to 100.0% (CI: 94.31–100.0%). Significant diagnostic value in discriminating pathologic stage was observed for ANRIL and MEG3 (p = 0.022, p = 0.0005). LncRNA show a significant change in expression in GBC and in discrimination of early stage from late-stage disease. The detection of 2 lncRNAs in panels, in coordination with radiology, could represent a potential serum-based biomarker for early-stage GBC diagnosis.
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spelling doaj.art-df5aa8a27aca48e882d37450ac1e9fd92024-03-31T04:37:50ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402024-06-0192583593Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinomaSridhar Mishra0Pallavi Srivastava1Anshuman Pandey2Akash Agarwal3Saumya Shukla4Nuzhat Husain5Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, IndiaDepartment of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, IndiaGastrosurgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, IndiaSurgical Oncology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, IndiaDepartment of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, IndiaDepartment of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226010, India; Corresponding author. Department of Pathology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, 226010, Uttar Pradesh, India.Gallbladder carcinoma (GBC) is a common malignancy and is usually diagnosed in the late stages of the disease. The identification of new effective early diagnostic biomarkers could represent an effective approach in reducing mortality in GBC. Altered expression of long non-coding RNAs (lncRNAs) is believed to be associated with the emergence and development of GBC. Our study aims to identify the expression of a range of circulating lncRNAs, including HOTAIR, ANRIL, H19, CCAT1 and MEG3, in matched serum and tissues of GBC for diagnosis and its association with clinicopathological features. The case and control study included matched serum and tissues from 63 GBC, 19 cholecystitis (CC), and 46 normal controls (NC). RNA extraction and cDNA synthesis from serum and fresh tissue match were performed using commercially available kits. Relative expression was assessed using SYBR Green real-time quantitative polymerase chain reaction. Circulating lncRNA levels including HOTAIR, ANRIL and H19 were upregulated in serum samples, while MEG3 and CCAT1 were downregulated in GBC compared to controls. The trend towards upregulation and downregulation was comparable in the tissue. HOTAIR and MEG3 levels were significantly different between serum CC and early-stage GBC (p = 0.0373, 0.0020), while H19 was significantly upregulated comparing early-stage GBC to advanced-stage GBC (p = 0.018). The expression of ANRIL was significant with M stage (p = 0.0488), H19 with stage (p = 0.009), M stage (p=<0.0001) &amp; stage (0.009) and CCAT1 with M stage (0.044). When distinguishing GBC and NC, AUC for HOTAIR was 0.75, ANRIL 0.78, H19 0.74, CCAT1 0.80 and 0.96 for MEG3. The combination sensitivity for lncRNAs ranged from 84.13% (CI: 72.74–92.12%) to 100.0% (CI: 94.31–100.0%). Significant diagnostic value in discriminating pathologic stage was observed for ANRIL and MEG3 (p = 0.022, p = 0.0005). LncRNA show a significant change in expression in GBC and in discrimination of early stage from late-stage disease. The detection of 2 lncRNAs in panels, in coordination with radiology, could represent a potential serum-based biomarker for early-stage GBC diagnosis.http://www.sciencedirect.com/science/article/pii/S246805402400026XGallbladder carcinomaLiquid biopsyLong non-coding RNAsEpigeneticsEarly diagnosis
spellingShingle Sridhar Mishra
Pallavi Srivastava
Anshuman Pandey
Akash Agarwal
Saumya Shukla
Nuzhat Husain
Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
Non-coding RNA Research
Gallbladder carcinoma
Liquid biopsy
Long non-coding RNAs
Epigenetics
Early diagnosis
title Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
title_full Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
title_fullStr Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
title_full_unstemmed Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
title_short Panel of serum long non-coding RNAs as potential non-invasive biomarkers for gallbladder carcinoma
title_sort panel of serum long non coding rnas as potential non invasive biomarkers for gallbladder carcinoma
topic Gallbladder carcinoma
Liquid biopsy
Long non-coding RNAs
Epigenetics
Early diagnosis
url http://www.sciencedirect.com/science/article/pii/S246805402400026X
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