BioMed Research International

BioMed Research International / 2020 / Article

Review Article | Open Access

Volume 2020 |Article ID 2810150 | https://doi.org/10.1155/2020/2810150

Xiaoxu Song, Wenyi Li, Peng Shen, Bing Bai, Lin-Lin Cao, "miR-19 Is a Potential Clinical Biomarker for Gastrointestinal Malignancy: A Systematic Review and Meta-analysis", BioMed Research International, vol. 2020, Article ID 2810150, 13 pages, 2020. https://doi.org/10.1155/2020/2810150

miR-19 Is a Potential Clinical Biomarker for Gastrointestinal Malignancy: A Systematic Review and Meta-analysis

Academic Editor: Xin-yuan Guan
Received20 Feb 2020
Revised15 Jun 2020
Accepted26 Jun 2020
Published10 Sep 2020

Abstract

Objectives. To assess the expression and clinical value of miR-19 in gastrointestinal malignancy. Setting. Embase, Web of Science, PubMed, and other databases were retrieved to screen out relevant studies until December 31, 2019. Participants. Gastrointestinal cancer patients with the description of miR-19 expression, as well as the correlation between miR-19 and clinicopathological characteristics or prognosis. Main Outcome Measures. Pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was obtained to determine miR-19 expression in gastrointestinal malignancy and the association between miR-19 and patients’ clinical characteristics and survival. Results. Thirty-seven studies were included in this study. miR-19 levels in gastrointestinal malignancy, especially in hepatocellular (, ), colorectal (, ), and pancreatic (, ) cancers, were significantly overexpressed, and miR-19 was tightly related to some clinicopathological characteristics, such as lymph node metastasis (, ). Although gastrointestinal cancer patients with low and high miR-19 expression had comparable OS (overall survival) and DFS (disease-free survival), subgroup analyses showed that patients with high miR-19 presented better DFS than those with low miR-19 in liver cancer (, ). Conclusions. miR-19 might be a potential progression and prognostic biomarker for gastrointestinal malignancy.

1. Background

Gastrointestinal malignancy is extremely harmful to humans, including gastric, pancreatic, esophageal, liver, and colorectal cancers and other types of cancer in the digestive tract. Their morbidity and mortality rates are really high, especially in less-developed countries [1]. Although great progress has been achieved in early diagnosis and therapy during the past few decades, the overall survival (OS) for gastrointestinal malignancy is still unsatisfactory [2]. Therefore, it is essential to identify novel biomarkers for patients’ early diagnosis and better prognosis.

MicroRNAs (miRNAs) are a kind of small noncoding RNA, which can modulate gene expression by cleaving targeted messenger RNA (mRNA) or repressing translation [3]. A number of studies have reported that miRNAs show the potential to be novel cancer biomarkers for early detection of cancer [46]. MicroRNA-19 (miR-19), which is one member of the large miRNA family, has been demonstrated to be tightly correlated with gastrointestinal malignancy [710]. However, the exact role of miR-19 in gastrointestinal malignancy is still unclear.

In the present study, a systematic review and meta-analysis was carried out to assess the association of miR-19 with gastrointestinal cancers. At first, miR-19 expression in gastrointestinal cancer tissue and normal tissue was compared, and then, the correlation of the miR-19 level with several clinical characteristics was evaluated. In addition, the role of miR-19 in prognosis for patients with gastrointestinal cancers was also determined.

2. Methods

2.1. Search Strategy and Inclusion Criteria

Original researches reporting the association of miR-19 with the progression or prognosis of gastrointestinal cancers were retrieved in Embase, Web of Science, PubMed, and other databases until December 31, 2019. No language restriction was used. We selected studies according to the following keywords: “miR-19”, “microRNA-19”, or “miRNA-19” for miR-19; “colorectal carcinoma” or “colorectal cancer” for colorectal cancer; “esophageal cancer” or “esophagus neoplasm” for esophageal cancer; “gastric neoplasm”, “gastric cancer”, or “stomach cancer” for gastric cancer; “liver cancer”, “hepatocellular carcinoma”, or “hepatocellular cancer” for liver cancer; and “pancreatic neoplasm” or “pancreatic cancer” for pancreatic cancer.

Then, full texts of the relevant studies were evaluated deeply. The inclusion criteria were the following: (1) the expression level of miR-19 was detected by PCR, (2) the clinicopathological parameters or patient survival of gastrointestinal cancers were investigated, and (3) the association of miR-19 with clinicopathological parameters or patient survival was assessed. Studies were excluded if (1) they were not original articles, such as letters, case reports, or reviews; (2) they were focusing on cancer cells or animal models, rather than human samples; or (3) the full texts were not available. Two authors, Xiaoxu Song and Lin-Lin Cao, performed the evaluations independently, and disagreement was settled according to the original article.

2.2. Data Extraction

Data were extracted by Xiaoxu Song and Wenyi Li independently. The extracted information included the first author’s name, country, publication year, age and number of patients, the method of miR-19 detection, cut-off point, histology, clinical stage, and survival. If the cut-off point of miR-19 was not described in the studies, the mean value was used as the cut-off point. If there was only a histogram and no original data for miR-19 expression were provided, Engauge Digitizer 4.1 was applied to extract the needed data. In addition, Engauge Digitizer 4.1 was also used for the survival data if there were only Kaplan-Meier curves in the included studies [11].

2.3. Quality Assessment

The quality evaluation of the retrieved studies was completed by Xiaoxu Song and Wenyi Li independently based on the Newcastle-Ottawa Scale (NOS), which includes three parts: sample selection, comparability, and exposure ascertainment.

2.4. Statistical Analysis

All analyses were carried out with Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). The odds ratio (OR) with 95% confidence interval (CI) was calculated to compare miR-19 levels between the tumor group and the control group and to analyze the correlation between miR-19 and clinicopathologic characters of gastrointestinal cancers. The association of miR-19 levels with patient prognosis was determined using the hazard ratio (HR) with 95% confidence interval (CI). The model of random effect was used if ; otherwise, the model of fixed effect was applied (). was statistically significant. The funnel plot was depicted to determine publication bias.

2.5. Patient and Public Involvement

There is no patient involved.

3. Results

3.1. Description of the Included Cohorts

In this analysis, 711 studies were identified through searching Embase, PubMed, and Web of Science, and 646 studies were identified in other databases. In total, 1357 studies were found initially (Figure 1). Then, 1274 studies were excluded due to their irrelevance or duplication after checking their titles and abstracts. The remaining 83 studies were read carefully in full text, and 46 were excluded as well because of the following two reasons: (1) there was no data of human samples but only cell lines or animal models or (2) relevant data was not available. Finally, 37 studies [7, 9, 10, 1245] were included in this analysis, including 12 studies focusing on colorectal cancer, 11 studies focusing on gastric cancer, 8 studies focusing on liver cancer, 2 study focusing on esophageal cancer, and 4 studies focusing on pancreatic cancer. Some characteristics and results of these studies are described in Table 1. Totally, 3472 cases were included in this analysis. All these studies used real-time polymerase chain reaction (RT-PCR) for miR-19 detection. NOS evaluation results suggested high quality of all the studies (Table 2).


StudyYearCountry or areaSample numberAgeDetection methodCut-off pointHistologyStageFollow-up period (month)Survival

Yamada2015USA48NRRT-PCR>medianCRCNRNRNR
Kahlert2011Germany29NRRT-PCRNRCRCNR60OS, RFS
Cellura2015UK10NRRT-PCR≥medianCRCNRNRNR
Huang2015China27560 (mean)RT-PCR≥0.22CRCI-IVNROS
Jiang2017China21165 (mean)RT-PCR>medianCRCI-IV59 (median)OS, DFS
Mastumura2015Japan20965 (mean)RT-PCRNRCRCI-IV60OS, DFS
Cruz-Gil2018Spain126NRRT-PCRNRCRCII-IIINRDFS
Koga2010Japan6260 (median)RT-PCR>medianCRCNRNRNR
Zhu2017China16660 (mean)RT-PCR>medianCRCI-IVNRNR
Zhang2018China5660 (mean)RT-PCR>medianCRCI-IV80OS
Yin2019China3050 (mean)RT-PCR>medianCRCI-IVNRNR
Marcuello2019Spain5962 (mean)RT-PCRNRCRCI-IVNRNR
Guo2014China5150 (mean)RT-PCR>medianHCCI-IV60OS
Han2012China10556.5 (mean)RT-PCRNRHCCI-IV80OS, DFS
Hu2018China20NRRT-PCR>medianHCCNRNRNR
Hung2015Taiwan8160 (mean)RT-PCR≥medianHCCII-IV37 (mean)OS, DFS
Yu2016China43NRRT-PCR≥medianHCCNRNRNR
Zhang2015China13050 (mean)RT-PCR≥medianHCCI-IV60OS, DFS
Zhu2010China9550 (mean)RT-PCRHCCI-III62.6 (mean)OS
Jiang2018China22NRRT-PCR≥medianHCCNRNRNR
Cai2016China60NRRT-PCR>medianGCNRNRNR
Li2014China3050 (mean)RT-PCRNRGCI-IVNRNR
Ibarrola-Villava2015Spain45NRRT-PCR≥medianGCNRNRNR
Wang2016China9065 (mean)RT-PCR>medianGCI-IV60OS, DFS
Wang2017China12060RT-PCRGCI-IVNRNR
Wu2014China14160 (mean)RT-PCR≥medianGCI-IV70OS
Zhu2018China18060 (mean)RT-PCRGCI-IVNRNR
Liu2018China8065.1 (mean)RT-PCR2.072GCI-IVNRNR
Li2018China42NRRT-PCR≥medianGCNRNRNR
Zhu2019China40NRRT-PCR≥medianGCNRNRNR
Peng2018China33359.42 (mean)RT-PCR≥medianGCI-IV60OS, PFS
Xu2014China10555 (mean)RT-PCRECI-IV34.5 (median)OS, PFS
Bai2017China8958 (mean)RT-PCR≥0.2909ECI-IVNRNR
Tan2015China58NRRT-PCR≥medianPCNRNROS
Qu2014China3965 (mean)RT-PCRNRPCI-IVNRNR
Zou2019China12960 (mean)RT-PCR>medianPCI-IVNROS
Hu2016China63NRRT-PCR≥medianPCNRNRNR

Abbreviations: NR: not reported; RT-PCR: real-time polymerase chain reaction; T/N: tumor/normal; CRC: colorectal cancer; EC: esophagus cancer; GC: gastric cancer; PC: pancreatic cancer; LC: liver cancer; OS: overall survival; DFS: disease-free survival; RFS: recurrence-free survival; PFS: progression-free survival.

StudySelectionComparabilityExposureTotal quality score

Yamada, 20153137
Kahlert, 20113238
Cellura, 20153036
Huang, 20153238
Jiang, 20173238
Mastumura, 20154239
Cruz-Gil, 20183137
Koga, 20103137
Zhu, 20173238
Zhang, 20183339
Yin, 20193328
Marcuello, 20193339
Guo, 20143227
Han, 20123238
Hu, 20183036
Hung, 20153238
Yu, 20163137
Zhang, 20153238
Zhu, 20103227
Jiang, 20183227
Cai, 20163238
Li, 20144239
Ibarrola-Villava, 20153238
Wang, 20164239
Wang, 20174239
Wu, 20143238
Zhu, 20183238
Liu, 20183339
Li, 20183227
Zhu, 20192327
Peng, 20183339
Xu, 20144239
Bai, 20173238
Tan, 20153036
Qu, 20142136
Zou, 20193238
Hu, 20163137

3.2. miR-19 Levels in Gastrointestinal Cancers Were Higher than Those in Noncancerous Controls

Most of the included studies have compared miR-19 levels between gastrointestinal cancers and noncancerous controls, including 7 studies focusing on colorectal cancer, 8 studies focusing on gastric cancer, 5 studies focusing on liver cancer, 3 studies focusing on pancreatic cancer, and only 1 study focusing on esophageal cancer. The result is shown in Figure 2 (, ), suggesting that miR-19 levels in gastrointestinal malignancy were higher than those in controls.

Then, we carried out subgroup analysis according to different cancers. As shown in Figure 3(a), miR-19 levels in liver cancer were higher than those in the control group (, ). Similar results were found in colorectal cancer (, ) and pancreatic cancer (, ) (Figures 3(b) and 3(d)). However, no significant distinction existed between gastric cancer and noncancerous group (Figure 3(c)). There was only one study focusing on esophageal cancer. Taken together, these data indicate that miR-19 levels in gastrointestinal cancers, especially colorectal, liver, and pancreatic cancers, were higher than those in noncancerous controls.

3.3. Association of miR-19 Expression with the Clinical Characteristics of Patients with Gastrointestinal Malignancy

Next, we determined the correlation between miR-19 and the clinicopathologic characteristics of patients with gastrointestinal malignancy. Unfortunately, there is no significant correlation between the miR-19 level and some clinical features, such as the tumor stage, differentiation degree, or distant metastasis of overall gastrointestinal cancers (Figures 46). Interestingly, we discovered that miR-19 levels were upregulated in lymph node metastasis-positive patients (, ) (Figure 7).

The results of subgroup analyses are displayed in Table 3. miR-19 levels in stages III-IV were higher than those in stage I-II colorectal cancer (, ). In addition, the miR-19 expression levels were lower in low-differentiated gastric tissues than those high-/moderate-differentiated ones (, ). There is no significant distinction in other analyses, and some analyses were short of studies (0 or 1 study), especially for esophagus and pancreatic cancers. Collectively, there are some relationship between miR-19 levels and clinicopathologic characteristics in gastrointestinal malignancy.


StageGradeLymph node metastasisDistant metastasis

Colorectal cancerOR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
62.74 (1.45, 5.18)31.36 (0.74, 2.51)71.89 (0.99, 3.63)82.02 (0.77, 5.32)
Gastric cancerOR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
20.42 (0.17, 1.04)20.31 (0.14, 0.70)30.46 (0.14, 1.52)10.31 (0.10, 0.97)
Esophagus cancerOR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
11.72 (0.95, 3.12)11.65 (0.86, 3.16)11.87 (0.91, 3.85)NoneNone
Liver cancerOR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
40.66 (0.18, 2.45)40.80 (0.47, 1.35)14.75 (1.37, 16.47)NoneNone
Pancreatic cancerOR (95% CI)OR (95% CI)OR (95% CI)OR (95% CI)
NoneNoneNoneNoneNoneNoneNoneNone

Abbreviations: : study numbers.
3.4. Influence of miR-19 on Clinical Outcome of Gastrointestinal Malignancy

Finally, the correlation between miR-19 and OS as well as disease-free survival (DFS) of gastrointestinal malignancy was investigated. Firstly, the analysis result showed that gastrointestinal cancer patients with low and high miR-19 expression showed comparable OS (Figure 8). Similar results were found in subgroup analyses for liver (Figure 9(a)), colorectal (Figure 9(b)), gastric (Figure 9(c)), and pancreatic (Figure 9(d)) cancers.

In addition, gastrointestinal cancer patients with low and high miR-19 expression showed comparable DFS as well (Figure 10). Subgroup analyses showed that the miR-19 level was positively associated with the DFS of liver cancer patients (, ) (Figure 11(a)), but not colorectal and gastric cancer patients (Figures 11(b) and 11(c)). There was short of study analyzing the DFS of esophageal and pancreatic cancer patients (0 or 1 study).

3.5. Sensitivity and Bias Analysis

We conducted sensitivity analysis by removing a cohort one time. Results of meta-analyses were not altered greatly, suggesting the stability of these analyses. In addition, no significant publication biases existed according to the symmetric funnel plots (Supplement Figures. 1-7).

4. Discussions

In this study, an analysis of 37 studies revealed a potential role of miR-19 in the progression and prognosis of gastrointestinal cancers. At first, miR-19 levels in gastrointestinal cancers are significantly higher than those in controls. In addition, the association of miR-19 expression with clinical characteristics, such as the clinical stage, tumor differentiation degree, and lymph node and distant metastasis state, was described in subgroup analysis. At last, we depicted that liver cancer patients with higher miR-19 levels showed better DFS than those with low miR-19.

miR-19 expression levels in different gastrointestinal malignancies are inconsistent. For liver and colorectal cancers, most studies showed that miR-19 is overexpressed in cancer patients compared with normal controls. However, miR-19 expression in gastric and pancreatic cancers is controversy. For example, it has been illustrated that the miR-19 levels were upregulated significantly in gastric cancer patients [19, 32], but another study [9] discovered that miR-19 levels were decreased in gastric tumors. In addition, the miR-19 level has been demonstrated to be upregulated in pancreatic cancer [18], but no difference between pancreatic cancer and control was observed in another study [31]. In this study, miR-19 levels in gastrointestinal malignancy were higher than those in the control generally. However, it is necessary to do much more work for pancreatic and esophagus cancers due to the limited number of included studies.

In the present study, significant correlation between miR-19 levels and lymph node metastasis was observed in gastrointestinal malignancy, suggesting the role of miR-19 as a potential biomarker to diagnose patients with lymph node metastasis. Although the correlations between miR-19 and clinical stage, tumor differentiation degree, or distant metastasis state in the overall gastrointestinal malignancy were not significant, subgroup analysis has shown that miR-19 has diagnostic value in specific cancer types. In addition, no correlation between miR-19 and OS or DFS of overall gastrointestinal malignancy was observed, but the miR-19 level was positively correlated with the DFS of liver cancer patients as depicted in subgroup analyses, indicating that miR-19 shows its potential as a prognostic biomarker for liver cancer and would be beneficial for screening out high-risk liver cancer patients.

5. Conclusions

This study revealed the clinical significance of the miR-19 level in gastrointestinal malignancy. miR-19 could be a potential clinical biomarker for the progress and survival evaluation for gastrointestinal cancers and used as a new target for gastrointestinal cancer treatment.

Conflicts of Interest

The authors declared no conflicts of interest.

Supplementary Materials

Supplementary 1. Figure 1: funnel plots of publication bias in the meta-analysis as shown in Figure 2.

Supplementary 2. Figure 2: funnel plots of publication bias in the meta-analysis of miR-19 expression and tumor stage.

Supplementary 3. Figure 3: funnel plots of publication bias in the meta-analysis of miR-19 expression and tumor differentiation degree.

Supplementary 4. Figure 4: funnel plots of publication bias in the meta-analysis of miR-19 expression and lymph node metastasis.

Supplementary 5. Figure 5: funnel plots of publication bias in the meta-analysis of miR-19 expression and distant metastasis.

Supplementary 6. Figure 6: funnel plots of publication bias in the meta-analysis of miR-19 expression and OS as shown in Figure 8.

Supplementary 7. Figure 7: funnel plots of publication bias in the meta-analysis of miR-19 expression and DFS as shown in Figure 10.

References

  1. J. Ferlay, I. Soerjomataram, R. Dikshit et al., “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012,” International Journal of Cancer, vol. 136, no. 5, pp. E359–E386, 2015. View at: Publisher Site | Google Scholar
  2. K. D. Crew and A. I. Neugut, “Epidemiology of gastric cancer,” World Journal of Gastroenterology, vol. 12, no. 3, pp. 354–362, 2006. View at: Publisher Site | Google Scholar
  3. D. P. Bartel, “MicroRNAs,” Cell, vol. 116, no. 2, pp. 281–297, 2004. View at: Publisher Site | Google Scholar
  4. R. Liu, X. Chen, Y. Du et al., “Serum microRNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer,” Clinical Chemistry, vol. 58, no. 3, pp. 610–618, 2012. View at: Publisher Site | Google Scholar
  5. C. Zhang, C. Wang, X. Chen et al., “Expression profile of microRNAs in serum: a fingerprint for esophageal squamous cell carcinoma,” Clinical Chemistry, vol. 56, no. 12, pp. 1871–1879, 2010. View at: Publisher Site | Google Scholar
  6. X. Zhou, W. Zhu, H. Li et al., “Diagnostic value of a plasma microRNA signature in gastric cancer: a microRNA expression analysis,” Scientific Reports, vol. 5, no. 1, article 11251, 2015. View at: Publisher Site | Google Scholar
  7. Z. B. Han, L. Zhong, M. J. Teng et al., “Identification of recurrence-related microRNAs in hepatocellular carcinoma following liver transplantation,” Molecular Oncology, vol. 6, no. 4, pp. 445–457, 2012. View at: Publisher Site | Google Scholar
  8. M. D. Giráldez, J. J. Lozano, G. Ramírez et al., “Circulating microRNAs as biomarkers of colorectal cancer: results from a genome-wide profiling and validation study,” Clinical Gastroenterology and Hepatology, vol. 11, no. 6, pp. 681–688.e3, 2013. View at: Publisher Site | Google Scholar
  9. H. Wang, M. Xiong, Y. Hu, Y. Sun, and Q. Ma, “MicroRNA-19b inhibits proliferation of gastric cancer cells by targeting B-cell CLL/lymphoma 3,” Oncology Reports, vol. 36, no. 4, pp. 2079–2086, 2016. View at: Publisher Site | Google Scholar
  10. Y. Bai, H. Lin, Z. Fang et al., “Plasma microRNA-19a as a potential biomarker for esophageal squamous cell carcinoma diagnosis and prognosis,” Biomarkers in Medicine, vol. 11, no. 5, pp. 431–441, 2017. View at: Publisher Site | Google Scholar
  11. J. F. Tierney, L. A. Stewart, D. Ghersi, S. Burdett, and M. R. Sydes, “Practical methods for incorporating summary time-to-event data into meta-analysis,” Trials, vol. 8, no. 1, 2007. View at: Publisher Site | Google Scholar
  12. L. Ma, H. Cai, J. Xu et al., “Integrated miRNA-risk gene-pathway pair network analysis provides prognostic biomarkers for gastric cancer,” OncoTargets and Therapy, vol. 9, pp. 2975–2986, 2016. View at: Publisher Site | Google Scholar
  13. D. Cellura, K. Pickard, S. Quaratino et al., “miR-19-mediated inhibition of transglutaminase-2 leads to enhanced invasion and metastasis in colorectal cancer,” Molecular Cancer Research, vol. 13, no. 7, pp. 1095–1105, 2015. View at: Publisher Site | Google Scholar
  14. S. Cruz-Gil, R. Sanchez-Martinez, M. G. de Cedron et al., “Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role,” Journal of Lipid Research, vol. 59, no. 1, pp. 14–24, 2018. View at: Publisher Site | Google Scholar
  15. B. Hu, W. G. Tang, J. Fan, Y. Xu, and H. X. Sun, “Differentially expressed miRNAs in hepatocellular carcinoma cells under hypoxic conditions are associated with transcription and phosphorylation,” Oncology Letters, vol. 15, no. 1, pp. 467–474, 2018. View at: Publisher Site | Google Scholar
  16. L. Huang, X. Wang, C. Wen et al., “Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer,” Scientific Reports, vol. 5, no. 1, article 13350, 2015. View at: Publisher Site | Google Scholar
  17. C. L. Hung, C. S. Yen, H. W. Tsai, Y. C. Su, and C. J. Yen, “Upregulation of microRNA-19b predicts good prognosis in patients with hepatocellular carcinoma presenting with vascular invasion or multifocal disease,” BMC Cancer, vol. 15, no. 1, 2015. View at: Publisher Site | Google Scholar
  18. M. Hu, The functional role and underlying mechanisms of micro RNA-19b in necrotizing pancreatitis and pancreatic ductal ademocarcinoma, [Ph.D. thesis], Shandong University Dissertation for Doctoral Degree, 2016.
  19. M. Ibarrola-Villava, M. J. Llorca-Cardeñosa, N. Tarazona et al., “Deregulation ofARID1A,CDH1,cMETandPIK3CAand target-related microRNA expression in gastric cancer,” Oncotarget, vol. 6, no. 29, pp. 26935–26945, 2015. View at: Publisher Site | Google Scholar
  20. T. Jiang, L. Ye, Z. Han et al., “miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses,” Journal of Experimental & Clinical Cancer Research, vol. 36, no. 1, 2017. View at: Publisher Site | Google Scholar
  21. X. M. Jiang, X. N. Yu, T. T. Liu et al., “microRNA-19a-3p promotes tumor metastasis and chemoresistance through the PTEN/Akt pathway in hepatocellular carcinoma,” Biomedicine & Pharmacotherapy, vol. 105, pp. 1147–1154, 2018. View at: Publisher Site | Google Scholar
  22. C. Kahlert, F. Klupp, K. Brand et al., “Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases,” Cancer Science, vol. 102, no. 10, pp. 1799–1807, 2011. View at: Publisher Site | Google Scholar
  23. Y. Koga, M. Yasunaga, A. Takahashi et al., “MicroRNA expression profiling of exfoliated colonocytes isolated from feces for colorectal cancer screening,” Cancer Prevention Research, vol. 3, no. 11, pp. 1435–1442, 2010. View at: Publisher Site | Google Scholar
  24. Y. Li, S. Lv, H. Ning et al., “Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by sponging miR-19a,” Biomedicine & Pharmacotherapy, vol. 108, pp. 1775–1782, 2018. View at: Publisher Site | Google Scholar
  25. Y. Li, Z. Xu, B. Li et al., “Epigenetic silencing of miRNA-9 is correlated with promoter-proximal CpG island hypermethylation in gastric cancer in vitro and in vivo,” International Journal of Oncology, vol. 45, no. 6, pp. 2576–2586, 2014. View at: Publisher Site | Google Scholar
  26. H. N. Liu, H. Wu, Y. J. Tseng et al., “Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer,” BMC Cancer, vol. 18, no. 1, 2018. View at: Publisher Site | Google Scholar
  27. M. Marcuello, S. Duran-Sanchon, L. Moreno et al., “Analysis of a 6-miRNA signature in serum from colorectal cancer screening participants as non-invasive biomarkers for advanced adenoma and colorectal cancer detection,” Cancers, vol. 11, no. 10, 2019. View at: Publisher Site | Google Scholar
  28. T. Matsumura, K. Sugimachi, H. Iinuma et al., “Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer,” British Journal of Cancer, vol. 113, no. 2, pp. 275–281, 2015. View at: Publisher Site | Google Scholar
  29. W. Peng, Y. N. Liu, S. Q. Zhu, W. Q. Li, and F. C. Guo, “The correlation of circulating pro-angiogenic miRNAs’ expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer,” Cancer Medicine, vol. 7, no. 8, pp. 3773–3791, 2018. View at: Publisher Site | Google Scholar
  30. C. Qu, The correlation analysis between the tranditional Chinese medicine ZHENG and the expression of plasma prognostic mi RNA in non-resectable pancreatic cancer [Ph.D Thesis], Fudan University Dissertation for Master Degree, 2014.
  31. Y. Tan, H. Yin, H. Zhang et al., “Sp1-driven up-regulation of miR-19a decreases RHOB and promotes pancreatic cancer,” Oncotarget, vol. 6, no. 19, pp. 17391–17403, 2015. View at: Publisher Site | Google Scholar
  32. N. Wang, L. Wang, Y. Yang, L. Gong, B. Xiao, and X. Liu, “A serum exosomal microRNA panel as a potential biomarker test for gastric cancer,” Biochemical and Biophysical Research Communications, vol. 493, no. 3, pp. 1322–1328, 2017. View at: Publisher Site | Google Scholar
  33. Q. Wu, Z. Yang, Y. An et al., “miR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour suppressor MXD1,” Cell Death & Disease, vol. 5, article e1144, no. 3, 2014. View at: Publisher Site | Google Scholar
  34. X. L. Xu, Y. H. Jiang, J. G. Feng, D. Su, P. C. Chen, and W. M. Mao, “MicroRNA-17, microRNA-18a, and microRNA-19a are prognostic indicators in esophageal squamous cell carcinoma,” The Annals of Thoracic Surgery, vol. 97, no. 3, pp. 1037–1045, 2014. View at: Publisher Site | Google Scholar
  35. A. Yamada, T. Horimatsu, Y. Okugawa et al., “Serum miR-21, miR-29a, and miR-125b are promising biomarkers for the early detection of colorectal neoplasia,” Clinical Cancer Research, vol. 21, no. 18, pp. 4234–4242, 2015. View at: Publisher Site | Google Scholar
  36. Q. Yin, P. P. Wang, R. Peng, and H. Zhou, “miR-19a enhances cell proliferation, migration, and invasiveness through enhancing lymphangiogenesis by targeting thrombospondin-1 in colorectal cancer,” Biochemistry and Cell Biology, vol. 97, no. 6, pp. 731–739, 2019. View at: Publisher Site | Google Scholar
  37. G. Yu, X. Chen, S. Chen, W. Ye, K. Hou, and M. Liang, “miR-19a, miR-122 and miR-223 are differentially regulated by hepatitis B virus X protein and involve in cell proliferation in hepatoma cells,” Journal of Translational Medicine, vol. 14, no. 1, 2016. View at: Publisher Site | Google Scholar
  38. J. L. Yuehu Guo, B. Wang, W. Zhao, and M. He, “miR-19 expression in hepatocellular carcinoma and its clinical significance,” Chinese Journal of General Surgery, vol. 23, no. 9, pp. 1217–1221, 2014. View at: Google Scholar
  39. J. Zhang, Z. Wang, X. Han et al., “Up-regulation of microRNA-19b is associated with metastasis and predicts poor prognosis in patients with colorectal cancer,” International Journal of Clinical and Experimental Pathology, vol. 11, no. 8, pp. 3952–3960, 2018. View at: Google Scholar
  40. Y. Zhang, X. Guo, Z. Li et al., “A systematic investigation based on microRNA-mediated gene regulatory network reveals that dysregulation of microRNA-19a/Cyclin D1 axis confers an oncogenic potential and a worse prognosis in human hepatocellular carcinoma,” RNA Biology, vol. 12, no. 6, pp. 643–657, 2015. View at: Publisher Site | Google Scholar
  41. F. Zhu, Q. Wu, Z. Ni, C. Lei, T. Li, and Y. Shi, “miR-19a/b and MeCP2 repress reciprocally to regulate multidrug resistance in gastric cancer cells,” International Journal of Molecular Medicine, vol. 42, no. 1, pp. 228–236, 2018. View at: Publisher Site | Google Scholar
  42. J.-J. Zhu, Experimental study on metastasis-related mir-185 and mir-19 in hepatocellular carcinoma initial experimental study on function of has-mir-19 [Ph.D Thesis], Soochow University Dissertation for Master Degree, 2010.
  43. M. Zhu, Z. Huang, D. Zhu et al., “A panel of microRNA signature in serum for colorectal cancer diagnosis,” Oncotarget, vol. 8, no. 10, pp. 17081–17091, 2017. View at: Publisher Site | Google Scholar
  44. Y. Zhu, L. Li, D. Hou et al., “MicroRNA-19a regulates the proliferation, migration and invasion of human gastric cancer cells by targeting CUL5,” Archives of Biochemistry and Biophysics, vol. 662, pp. 93–100, 2019. View at: Publisher Site | Google Scholar
  45. X. Zou, J. Wei, Z. Huang et al., “Identification of a six-miRNA panel in serum benefiting pancreatic cancer diagnosis,” Cancer Medicine, vol. 8, no. 6, pp. 2810–2822, 2019. View at: Publisher Site | Google Scholar

Copyright © 2020 Xiaoxu Song et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder
Views71
Downloads52
Citations

Related articles

We are committed to sharing findings related to COVID-19 as quickly as possible. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Review articles are excluded from this waiver policy. Sign up here as a reviewer to help fast-track new submissions.