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. 2019 Jun 17:7:e7002.
doi: 10.7717/peerj.7002. eCollection 2019.

Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer

Jianlin Chen #  1 , Lihua Wu #  2 , Yifan Sun  1 , Qi Yin  1 , Xianhua Chen  1 , Siqun Liang  1 , Qingyan Meng  1 , Haihua Long  2 , Fangying Li  2 , Changjun Luo  3 , Xiaorong Xiao  4
Affiliations

Mir-421 in plasma as a potential diagnostic biomarker for precancerous gastric lesions and early gastric cancer

Jianlin Chen et al. PeerJ. .

Abstract

Objective: MicroRNA (miR)-421 plays a key role in cancer progression. It has been reported that circulating miR-421may be a potential tumor marker for the diagnosis of several cancers. However, the role of miR-421 in plasma as a potential biomarker in the diagnosis of precancerous gastric lesions (Pre) and early-stage gastric cancer (GC) remains poorly understood. In this study, we investigated miR-421 in plasma as a novel potential biomarker for the detection of precancerous gastric lesions and early-stage (GC).

Materials & methods: The miRNA content was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-421 content in all subjects was normalized by endogenous miRNA (miR-16). The diagnostic value of miR-421 for Pre and GC was assessed by comparing receiver operating characteristic (ROC) analysis with traditional tumor markers, including CEA, CA125, CA153, CA211 and CA50. The correlation between the expression of miR-421 and the pathological characteristics of Pre and GC was analyzed.

Results: Elevated expression of miR-421 in plasma can robustly distinguish the normal population from Pre and GC cases, especially in the early stages of gastric cancer cases (all p < 0.05). The ROC analyses showed that the area under the ROC curve (AUC), sensitivity, accuracy and Youden index of miR-421 were superior to traditional tumor markers (CEA, CA125, CA153, CA211, and CA50) in GC diagnosis, while its specificity was higher than CEA, CA153 and CA50 (all p < 0.05). MiR-421 in plasma had higher AUC value than AFP, CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05), while specificity, accuracy and Youden index of miR-421 was only lower than CA211. The efficiency of miR-421 in the diagnosis of GC was significantly higher than that of CA211 and CA50, and it was significantly higher than CA153, CA211 and CA50 in the diagnosis of Pre (all p < 0.05). In addition, up-regulation of miR-421 occurred initially in precancerous gastric lesions as well as in the early stage of GC.

Conclusions: Overexpression of plasma miR-421 is a novel biomarker for the detection of precancerous lesions and early gastric cancer.

Keywords: Early diagnosis; Gastric cancer; MicroRNA-421; Precancerous lesions.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. MiR-421 expression level between different groups (A) Differential expression levels of reference miR-16 (#p > 0.05). (B) The ΔCt values of miR-421 between different groups (∗∗∗∗p < 0.0001). (C) The levels (2−ΔCt) of miR-421 between different groups (∗∗∗∗p < 0.0001).
The ΔCt values denote the normalized Ct value by subtracting the Ct value of miR-16 from that of miR-421. The lower ΔCt value means the higher level of miR-421 expression. The Mann–Whitney U test was used to determine statistical significance at the level of p < 0.05.
Figure 2
Figure 2. The ROC curves of miR-421 and traditional tumor markers for GC.
(A) The AUC of miR-421was 0.981 (p < 0.05). (B) The AUC of CEA, CA50, CA125, CA153 and CA211 were 0.672, 0.754, 0.645, 0.656 and 0.799, respectively (all p < 0.05).
Figure 3
Figure 3. MiR-421 could distinguish early stage gastric cancer patients from healthy controls.
(A) MiR-421 was up-regulated in early stages (TNM stage I–II) gastric cancer patients compared to healthy controls (∗∗∗∗p < 0.0001). (B) The ROC analysis for detection of early-stages gastric cancer patients from health controls using miR-421.
Figure 4
Figure 4. miR-421 had higher diagnostic value than traditional tumor markers for precancerous patients.
Differential expression levels of CA50 (A) and CA211 (B) between precancerous patients and healthy controls (∗p < 0.01, ∗∗∗∗p < 0.0001). The ROC analysis for detection of precancerous using miR-421 (C) and traditional tumor markers CA50 and CA211 (D).
Figure 5
Figure 5. MiR-421 expression levels in plasma of GC cases with different TNM stages, PLGC cases and NC controls.
Mann–Whitney U test was used to determine statistical significance, p < 0.05 was accepted as statistically significant. ∗p < 0.05, ∗∗∗∗p < 0.0001, #p > 0.05.
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