Serum microRNAs as Biomarkers for the Noninvasive Early Diagnosis of Biliary Tract Cancer

Han, Yueting; Zhang, Haiyang; Zhou, Zhengyang; Li, Rui; Li, Dongying; Bai, Ming; Fan, Qian; Li, Jialu; Zhu, Kegan; Liu, Hongli; Ning, Tao; Ying, Guoguang; Ba, Yi

doi:10.2147/ijgm.s297371

Cited by 8 publications

(9 citation statements)

References 42 publications

(46 reference statements)

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“…Various nucleic acids (e.g.miRNAs), freely circulating or exosome bound, and CTCs with potential theranostic utilities have been described, although many still require validation in collaborative studies (5). Among these, mIR-21 and miR-221 levels have been commonly reported to have diagnostic value across several studies (141)(142)(143)182). The correlation of such novel biomarkers with CA19-9 levels is likely to further improve their diagnostic accuracies (81,143).…”

Section: Discussionmentioning

confidence: 99%

“…Among these, mIR-21 and miR-221 levels have been commonly reported to have diagnostic value across several studies (141)(142)(143)182). The correlation of such novel biomarkers with CA19-9 levels is likely to further improve their diagnostic accuracies (81,143). Advances in molecular profiling and sampling techniques have improved researchers' understanding of CCA evolution.…”

Section: Discussionmentioning

confidence: 99%

“…However, miR-21 was also found upregulated in other cancers including HCC, questioning its specificity (162). Outstanding from a panel of five miRs (miR-10a, miR-21, miR-135b, miR-221, and miR-214), exosome derived miR-221 levels alone differentiated malignant (n=75) from benign (n=20) and 68 healthy samples (p<0.01) in a recent study published by Han et al (143). The authors suggested a role for miR-221, in the early detection of BTCs (143).…”

Section: Cell-free Non-coding Rnamentioning

confidence: 98%

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Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

et al. 2021

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Cholangiocarcinoma is an uncommon and highly aggressive biliary tract malignancy with few manifestations until late disease stages. Diagnosis is currently achieved through a combination of clinical, biochemical, radiological and histological techniques. A number of reported cancer biomarkers have the potential to be incorporated into diagnostic pathways, but all lack sufficient sensitivity and specificity limiting their possible use in screening and early diagnosis. The limitations of standard serum markers such as CA19-9, CA125 and CEA have driven researchers to identify multiple novel biomarkers, yet their clinical translation has been slow with a general requirement for further validation in larger patient cohorts. We review recent advances in the diagnostic pathway for suspected CCA as well as emerging diagnostic biomarkers for early detection, with a particular focus on non-invasive approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cell-free Non-coding Rnamentioning

confidence: 98%

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Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

et al. 2021

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“…Many studies have reported speci c upregulation or downregulation of serum miRNAs in certain types of cancers [9,[11][12][13][14][15][16][17][18][31][32][33][34][35]. Yet, few studies have investigated the potential of serum miRNAs as a general cancer screening markers across multiple cancer subtypes [6,19].…”

Section: Discussionmentioning

confidence: 99%

Identification of Four Serum miRNAs as Potential Markers to Screen for Thirteen Cancer Types

Chen¹,

Dhahbi²

2021

Preprint

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Introduction: Cancer has consistently remained one of the top causes of death in the United States every year, with many cancer deaths preventable if detected early. Circulating serum miRNAs pose as a promising, minimally invasive supplement, or even alternative, to many current screening procedures. Many studies have shown that different serum miRNAs can discriminate healthy individuals from those with certain types of cancer. Although many of those miRNAs are often reported to be significant in one cancer type, they are also altered in other types of cancers. Currently, very few studies have investigated serum miRNA biomarkers for multiple different cancer types simultaneously for general cancer screening.Method: To identify serum miRNAs that would be useful in simultaneously screening multiple types of cancers, microarray cancer datasets were curated, yielding 13 different types of cancer with a total of 3352 cancer samples and 2809 non-cancer samples. The samples were then divided into discovery and validation sets. A hundred random forest models were built using the discovery set to select candidate miRNAs. The selected miRNAs were then used in the validation set to see how well they can differentiate cancer from normal samples in an independent dataset. Further analysis of the interactions between these miRNAs and their target mRNAs were investigated as well.Result: The random forest models achieved an average of 97% accuracy in the discovery set with 95% bootstrap confidence interval from 0.9544 to 0.9778. The selected miRNAs were hsa-miR-663a, hsa-miR-6802-5p, hsa-miR-6784-5p, hsa-miR-3184-5p, and hsa-miR-8073. Each individual miRNA exhibited high area under the curve (AUC) value using receiver operating characteristic analysis. Moreover, the combination of four out of the five miRNAs achieved the highest AUC value of 0.9815 with perfect sensitivity, indicating that these miRNAs have a high potential for cancer screening. miRNA-mRNA interaction and protein-protein interaction analysis provided insights into how these miRNAs may play a role in cancer in general.

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“…Although surgical resection is important for curative treatment, the disease is often advanced at the time of diagnosis, due to the tumor location and asymptomatic nature of the disease. Palliative chemotherapy is the only treatment option for inoperable patients [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

Park

Sung

Kim

et al. 2022

Cancers

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Some BTC types respond to pembrolizumab, but there are no known prognostic factors to predict its treatment benefits. In this study, we attempted to identify the prognostic factors associated with pembrolizumab as a second-line treatment for gemcitabine-refractory BTC. This retrospective and single tertiary-center study involved all the consecutive patients (n = 80) with refractory advanced BTC, who were diagnosed as programmed cell death ligand 1-positive and treated with pembrolizumab between August 2017 and February 2021. The overall survival (OS) was analyzed using Cox regression analysis. The median OS was 6.0 months [95% confidence interval (CI): 3.87–8.20]; median progression-free survival was 1.9 months (95% CI: 1.82–1.98); and the response rate was 15.9%. In the multivariate Cox regression analysis, the TB [adjusted hazard ratio (HR) = 2.286; 95% CI: 1.177–4.440; p = 0.015), albumin levels (adjusted HR = 0.392; 95% CI: 0.211–0.725; p = 0.003), ALP levels (adjusted HR = 1.938; 95% CI: 1.105–3.400; p = 0.021), and LMR (adjusted HR = 0.325; 95% CI: 0.173–0.609; p < 0.001) were identified as significant variables associated with the OS. High albumin levels and LMR and low ALP levels and TB were significantly associated with better OS in patients treated with pembrolizumab.

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Serum microRNAs as Biomarkers for the Noninvasive Early Diagnosis of Biliary Tract Cancer

Cited by 8 publications

References 42 publications

Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

Biliary Strictures and Cholangiocarcinoma – Untangling a Diagnostic Conundrum

Identification of Four Serum miRNAs as Potential Markers to Screen for Thirteen Cancer Types

Prognostic Factors in Patients Treated with Pembrolizumab as a Second-Line Treatment for Advanced Biliary Tract Cancer

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