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Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer.

Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, Chen Y, Pan F, Wang K, Ni J, Jin W, He X, Su H, Cui D - Theranostics (2015)

Bottom Line: And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05).The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p).Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy.

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P. R. China.

ABSTRACT
Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< r s<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future.

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Related in: MedlinePlus

Differential expression levels of miR-16-5p (A, C, E) and miR-19b-3p (B, D, F) normalized to the exogenous miRNA in the total training and validation phases. (A, B) Boxcharts respectively between GC cases with different TNM stages and N controls. (C, D) Boxcharts respectively between GC cases with different differentiation grades and N controls. (E, F) Boxcharts between GC cases with T1 stage and those with the others. T1-4 and G1-3, as stated in Table 3; h16c39 and h19bc39, as stated in Fig. 3. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05.
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Figure 5: Differential expression levels of miR-16-5p (A, C, E) and miR-19b-3p (B, D, F) normalized to the exogenous miRNA in the total training and validation phases. (A, B) Boxcharts respectively between GC cases with different TNM stages and N controls. (C, D) Boxcharts respectively between GC cases with different differentiation grades and N controls. (E, F) Boxcharts between GC cases with T1 stage and those with the others. T1-4 and G1-3, as stated in Table 3; h16c39 and h19bc39, as stated in Fig. 3. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05.

Mentions: There was significant difference of the two miRNAs for all the four TNM stages compared with N controls (P<0.05) (Fig. 5A, B). And it can be seen that the Ct value of the normalized miR-16-5p (h16c39) increased stepwisely with the TNM stage ranging from Ⅰ to Ⅳ(Fig. 5A and Table 3), while miR-19b-3p normalized to the exogenous miRNA (h19bc39) moderately increased to the peak in TNM Ⅲ stage , and then decreased in Ⅳ stage (Fig. 5B and Table 3). The case for miR-19b-3p normalized to the two reference miRNAs (h19bavec39h16) was similar with h19bc39 (Supplementary Material: Fig. S2A and Table S4). Correspondingly, FC between GC and N groups reached the minimum for GC cases in TNM Ⅲ or Ⅳ stage, which was 0.347 for h16c39, 0.258 for h19bc39 and 0.414 for h19bavec39h16, respectively (Table 3 and Supplementary Material: Table S4). It should be noted that miR-16-5p and miR-19b-3p in TNM Ⅰ stage were found significantly different from the other three stages (P<0.05) (Fig. 5E, F and Supplementary Material: Fig. S2C). More importantly, the expression level of the two miRNA biomarkers correlated with TNM stage of GC cases (0.2 <rs<0.3, P<0.01) (Table 4). Summarily, the results revealed that with the progression of the GC cases from the early stage to the advanced stage, the down-regulation of miR-16-5p and miR-19b-3p became more and more prominent.


Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer.

Zhang J, Song Y, Zhang C, Zhi X, Fu H, Ma Y, Chen Y, Pan F, Wang K, Ni J, Jin W, He X, Su H, Cui D - Theranostics (2015)

Differential expression levels of miR-16-5p (A, C, E) and miR-19b-3p (B, D, F) normalized to the exogenous miRNA in the total training and validation phases. (A, B) Boxcharts respectively between GC cases with different TNM stages and N controls. (C, D) Boxcharts respectively between GC cases with different differentiation grades and N controls. (E, F) Boxcharts between GC cases with T1 stage and those with the others. T1-4 and G1-3, as stated in Table 3; h16c39 and h19bc39, as stated in Fig. 3. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4402497&req=5

Figure 5: Differential expression levels of miR-16-5p (A, C, E) and miR-19b-3p (B, D, F) normalized to the exogenous miRNA in the total training and validation phases. (A, B) Boxcharts respectively between GC cases with different TNM stages and N controls. (C, D) Boxcharts respectively between GC cases with different differentiation grades and N controls. (E, F) Boxcharts between GC cases with T1 stage and those with the others. T1-4 and G1-3, as stated in Table 3; h16c39 and h19bc39, as stated in Fig. 3. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05.
Mentions: There was significant difference of the two miRNAs for all the four TNM stages compared with N controls (P<0.05) (Fig. 5A, B). And it can be seen that the Ct value of the normalized miR-16-5p (h16c39) increased stepwisely with the TNM stage ranging from Ⅰ to Ⅳ(Fig. 5A and Table 3), while miR-19b-3p normalized to the exogenous miRNA (h19bc39) moderately increased to the peak in TNM Ⅲ stage , and then decreased in Ⅳ stage (Fig. 5B and Table 3). The case for miR-19b-3p normalized to the two reference miRNAs (h19bavec39h16) was similar with h19bc39 (Supplementary Material: Fig. S2A and Table S4). Correspondingly, FC between GC and N groups reached the minimum for GC cases in TNM Ⅲ or Ⅳ stage, which was 0.347 for h16c39, 0.258 for h19bc39 and 0.414 for h19bavec39h16, respectively (Table 3 and Supplementary Material: Table S4). It should be noted that miR-16-5p and miR-19b-3p in TNM Ⅰ stage were found significantly different from the other three stages (P<0.05) (Fig. 5E, F and Supplementary Material: Fig. S2C). More importantly, the expression level of the two miRNA biomarkers correlated with TNM stage of GC cases (0.2 <rs<0.3, P<0.01) (Table 4). Summarily, the results revealed that with the progression of the GC cases from the early stage to the advanced stage, the down-regulation of miR-16-5p and miR-19b-3p became more and more prominent.

Bottom Line: And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05).The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p).Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy.

View Article: PubMed Central - PubMed

Affiliation: 1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P. R. China.

ABSTRACT
Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< r s<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future.

Show MeSH
Related in: MedlinePlus