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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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Expression levels of miR-19b-3p in the supplementary phase Ⅱ. (A) Boxcharts of the expression levels of miR-19b-3p. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05. (B, C) Column charts of the differential expression levels of miR-19b-3p between pre-operative gastric cancer patients (pre) and post-operative ones (pos). ΔΔCt(pos-pre) denotes the difference of the normalized Ct value. Paired Wilcoxon test was used to determine statistical significance at the level of P<0.05. h19b, h16c39, h19bc39 and h19bavec39h16 were stated as in Fig.3.
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Figure 8: Expression levels of miR-19b-3p in the supplementary phase Ⅱ. (A) Boxcharts of the expression levels of miR-19b-3p. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05. (B, C) Column charts of the differential expression levels of miR-19b-3p between pre-operative gastric cancer patients (pre) and post-operative ones (pos). ΔΔCt(pos-pre) denotes the difference of the normalized Ct value. Paired Wilcoxon test was used to determine statistical significance at the level of P<0.05. h19b, h16c39, h19bc39 and h19bavec39h16 were stated as in Fig.3.

Mentions: Between the pre-operative patients and the post-operative identical ones the differential expression was found statistically significant solely for miR-19b-3p. As depicted in Fig. 8A, there was significant difference of miR-19b-3p under two normalization methods both by Mann-Whitney U test and Wilcoxon test at the level of P<0.05. And the Ct values of miR-19b-3p for most of the participants increased after operation (Fig. 8B, C) with 0.630 and 0.560 folds of down-regulation respectively for h19bc39 and h19bavec39h16 (Supplementary Material: Table S6).


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)

Expression levels of miR-19b-3p in the supplementary phase Ⅱ. (A) Boxcharts of the expression levels of miR-19b-3p. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05. (B, C) Column charts of the differential expression levels of miR-19b-3p between pre-operative gastric cancer patients (pre) and post-operative ones (pos). ΔΔCt(pos-pre) denotes the difference of the normalized Ct value. Paired Wilcoxon test was used to determine statistical significance at the level of P<0.05. h19b, h16c39, h19bc39 and h19bavec39h16 were stated as in Fig.3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402497&req=5

Figure 8: Expression levels of miR-19b-3p in the supplementary phase Ⅱ. (A) Boxcharts of the expression levels of miR-19b-3p. Mann-Whitney U test was used to determine statistical significance at the level of P<0.05. (B, C) Column charts of the differential expression levels of miR-19b-3p between pre-operative gastric cancer patients (pre) and post-operative ones (pos). ΔΔCt(pos-pre) denotes the difference of the normalized Ct value. Paired Wilcoxon test was used to determine statistical significance at the level of P<0.05. h19b, h16c39, h19bc39 and h19bavec39h16 were stated as in Fig.3.
Mentions: Between the pre-operative patients and the post-operative identical ones the differential expression was found statistically significant solely for miR-19b-3p. As depicted in Fig. 8A, there was significant difference of miR-19b-3p under two normalization methods both by Mann-Whitney U test and Wilcoxon test at the level of P<0.05. And the Ct values of miR-19b-3p for most of the participants increased after operation (Fig. 8B, C) with 0.630 and 0.560 folds of down-regulation respectively for h19bc39 and h19bavec39h16 (Supplementary Material: Table S6).

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