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Aging and disease    2015, Vol. 6 Issue (6) : 478-485     DOI: 10.14336/AD.2015.0620
Original Article |
Overexpression of miR-1260b in Non-small Cell Lung Cancer is Associated with Lymph Node Metastasis
Xu Limin1, Li Liqin1, Li Jing1, Li Hongwei2, Shen Qibin2, Ping Jinliang3, Ma Zhihong1, Zhong Jing1, Dai Licheng1,*()
1 Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China
2 Department of Thoracic Surgery, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China
3 Department of Pathology, Huzhou Central Hospital, Huzhou, Zhejiang, 313000, China
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Abstract  

Lymph node (LN) metastasis is often an early event in the progression of malignant tumors and it contributes to the majority of cancer mortalities. MiRNAs play key roles in tumor metastasis. This study aimed to investigate the specific miRNAs as putative indicators of metastasis early diagnosis for non-small cell lung cancer (NSCLC). In this study, five NSCLC cases with LN metastasis and four cases without metastasis (NLN) were enrolled for Agilent Human miRNA array. The interested differentially expressed miRNA was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the LN metastasis (n = 46) and NLN (n = 39) groups. The microarray results revealed that three miRNAs (miR-1260b, miR-423-3p, miR-23a-5p) were differentially expressed in LN metastasis group compared with NLN group. The expression of miR-1260b was tested by qRT-PCR and the mean relative expression fold change (2-ΔΔCt) in LN metastasis was significantly higher than that in the NLN group (3.942, 1.743 respectively, P = 1.179E-04). The patients with tumor-node-metastasis (TNM) stage III were identified more frequently in LN metastasis group (P = 1.772E-11) and with a higher expression level of miR-1260b (5.126, P = 1.147E-06). In addition, the LN metastasis cases were associated with a poorly differentiated degree (P = 0.007). The overexpression of miR-1260b in NSCLC with LN metastasis can be regarded as a specific signature for early progression and prognosis of NSCLC.

Keywords non-small cell lung cancer      lymph node metastasis      miR-1260b     
Corresponding Authors: Dai Licheng     E-mail: dlc21@126.com
About author:

present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 December 2015
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Xu Limin
Li Liqin
Li Jing
Li Hongwei
Shen Qibin
Ping Jinliang
Ma Zhihong
Zhong Jing
Dai Licheng
Cite this article:   
Xu Limin,Li Liqin,Li Jing, et al. Overexpression of miR-1260b in Non-small Cell Lung Cancer is Associated with Lymph Node Metastasis[J]. Aging and disease, 2015, 6(6): 478-485.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2015.0620     OR     http://www.aginganddisease.org/EN/Y2015/V6/I6/478
Figure 1.  Change of miRNAs in the LN metastasis group. (A) Volcano plot shows the fold change of miRNAs in the LN metastasis group compared to NLN group. The vertical lines correspond to 2.0-fold up and down respectively, and the horizontal line represents a P value of 0.05. The colored points in the plot represent the differentially expressed miRNAs with statistical significance. (B) Hierarchical clustering for differentially expressed miRNAs in the LN metastasis group versus NLN group using a volcano plot (fold change ≥ 0.5). Red indicates high relative expression and green indicates low relative expression.
MiRNAFold -change (LN/NLN)P value
Hsa-miR-1260b2.6840.012
Hsa-miR-23a-5p0.0490.021
Hsa-miR-423-3p0.0570.010
Table 1  Expression level of miRNAs in LN metastasis and NLN groups
miRNAPathway IDKEGG nameGene countGene list
miR-1260b
hsa04310Wnt signaling pathway8GPC4,CCND2,CSNK2B,NKD1,FZD5,SOST,TCF7,SFRP1
hsa04350TGF-beta signaling pathway3SP1,INHBB,ZFYVE9
hsa05223Non-small cell lung cancer2SOS1,RXRA
hsa04115p53 signaling pathway2CCND2,CHEK1
hsa04514Cell adhesion molecules (CAMs)1NRXN2
hsa04010MAPK signaling pathway7SOS1,MKNK2,DUSP3,ELK1,TAOK2,DUSP16,ELK4
hsa05200Pathways in cancer8SOS1,RXRA,FLT3,FZD5,TCF7,TRAF4,ABL1,ETS1
hsa04668TNF signaling pathway2ATF6B,NOD2
miR-423-3p
hsa04010MAPK signaling pathway1FGFR2
hsa05200Pathways in cancer1FGFR2
miR-23a-5p
hsa04514Cell adhesion molecules (CAMs)3CNTN1,PDCD1,JAM3
hsa04668TNF signaling pathway1CSF1
hsa04310Wnt signaling pathway1NKD1
hsa05200Pathways in cancer1ARNT
hsa04010MAPK signaling pathway1STK3
Table 2  Predicated gene targets of the differentially expressed miRNAs with Gene Ontology (GO) analysis
LN (n = 46)NLN (n = 39)P
Age62.826 ± 7.15962.231 ± 7.4780.709
Gender0.417
Male2827
Female1812
TNM stage1.772E-11
I017
II1820
III282
Tumor type0.481
Adenocarcinoma3122
Squamous carcinoma1114
Other type of NSCLC43
Differentiation0.007
Poorly127
Moderately and poorly218
Moderately1324
Table 3  Clinical characteristics of NSCLC patients in the validation cohort (n = 44)
Figure 2.  The miRNA expression level of has-miR-1260b detected by qRT-PCR in the LN metastasis and NLN groups. Error bars in the figure represent Mean ± SD. LN: lymph node metastasis; NLN: lymph node free.
Figure 3.  The miRNA expression level of has-miR-1260b in different TNM stages. Error bars in the figure represent Mean ± SD.Ⅰ: TNM stage Ⅰ; Ⅱ: TNM stage Ⅱ; Ⅲ: TNM stage Ⅲ.
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