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. 2017 Feb 16:7:42806.
doi: 10.1038/srep42806.

Prognostic Value of microRNA Signature in Patients with Gastric Cancers

Hai-Ting Liu  1   2 , Ya-Wen Wang  1   2 , Ai-Yan Xing  1   2 , Duan-Bo Shi  1   2 , Hui- Zhang  1 , Xiang-Yu Guo  1   2 , Jing- Xu  2   3 , Peng Gao  1   2
Affiliations

Prognostic Value of microRNA Signature in Patients with Gastric Cancers

Hai-Ting Liu et al. Sci Rep. .

Abstract

The occurrence of lymph node metastases (LNM) after endoscopic submucosal dissection (ESD) in patients with gastric cancer (GC) leads to poor prognosis. However, few biomarkers are available to predict LNM in GC patients. Thus, we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC samples that were randomized into a training set and a testing set (each, 51 cases). Using logistic regression, we identified 4-miRNA (miR-27b, miR-128, miR-100 and miR-214) signatures for predicting LNM in GC patients. Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores. Meanwhile, the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients. In addition, Cox regression analysis indicated that a 2-miRNA signature (miR-27b and miR-214) or a miR-214/N stage signature was predictive of survival for GC patients. This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients' survival.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Expression of six cancer-related miRNAs and accuracy for predicting LNM in GC training sets.
Expression of miR-27b (A), miR-101 (B), miR-128 (C), miR-100 (D) and miR-214 (F) in patients with LNM were significantly lower than for patients without LNM (all p < 0.05). No correlation was found between expression of miR-145 (E) and LNM (p > 0.05). AUC for miRNAs. (A) miR-27b (p = 0.0097); (B) miR-101 (p = 0.00824); (C) miR-128 (p = 0.00069); (D) miR-100 (p = 0.0106); (E) miR-145 (p = 0.1649); (F) miR-214 (p = 0.0128).
Figure 2
Figure 2. Expression of six cancer-related miRNAs and accuracy for predicting patients with LNM in GC testing sets.
Expression of miR-27b (A), miR-128 (C), miR-100 (D) and miR-214 (F) in patients with LNM were significantly lower than for patients without LNM (all p < 0.05). No correlation was found between expression of miR-101 (B) and miR-145 (E) and LNM (all p > 0.05). AUC for the miRNAs. (A) miR-27b (p = 0.0043);(B) miR-101 (p = 0.1503); (C) miR-128 (p = 0.0228); (D) miR-100 (p = 0.0014); (E) miR-145 (p = 0.2795); (F) miR-214 (p = 0.0017).
Figure 3
Figure 3. Expression of six cancer-related miRNAs and accuracy for predicting patients with LNM from both GC sets.
Expression of miR-27b (A), miR-128 (C), miR-100 (D) and miR-214 (F) in patients with LNM were significantly lower than for patients without LNM (all p < 0.05). No correlation was found between expression of miR-101 (B) and miR-145 (E) and LNM (all p > 0.05). AUC for the miRNAs. (A) miR-27b (p < 0.0001); (B) miR-101 (p = 0.0026); (C) miR-128 (p = 0.0002); (D) miR-100 (p < 0.0001); (E) miR-145 (p = 0.0720); (F) miR-214 (p = 0.0001).
Figure 4
Figure 4. Expression changes in individual miRNA in GC samples with and without LNM.
Heat map diagram: red represents overexpression; green represents underexpression; black represents unchanged.
Figure 5
Figure 5
(A) Patients with high risk-scores tended to have higher LNM in GC patients than did those with low risk scores. (B) The four-miRNA signature can predict LNM in GC patients with higher AUC (p < 0.0001), indicating the considerable clinical value to predict LNM in GC patients. (C) miR-214/N stage signature can predict survival in GC patients with higher AUC (p = 0.00477), indicting the miR-214/N stage signature had better prognostic value than that of miR-214 or N stage alone for patients with gastric cancer. The combination of miRNAs (miR-27b and miR-214) (F, p = 0.0243) better predicted survival than miR-27b (D, p = 0.0403) and miR-214 (E, p = 0.0480) with respect to OS.
Figure 6
Figure 6. Expression of six cancer-related miRNAs and correlation with GC patient survival.
Kaplan-Meier survival analysis and log-rank test showed that patients with lower miR-27b (A) and miR-214 (F) had a poorer OS. However, there was no significant difference in OS between the miR-101 (B), miR-128 (C), miR-100 (D) and miR-145 (E) lower and higher expression groups.
See this image and copyright information in PMC

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