Serum miR-658 induces metastasis of gastric cancer by activating PAX3-MET pathway: A population-based study
Authors: Fujian Ji
Yuanyu Wu
Zheyu Song
Xiaoyu Wan
Xuedong Fang
Journal: Cancer Biomarkers (2018)
Discipline: CLINICAL MEDICINE
Keywords: Met proto-oncogene; metastasis of gastric carcinoma; miR-658; paired box gene 3.
Affiliations: Department of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China., Department of Breast and Thyroid Surgery, The Second Hospital of Jilin University, Changchun, Jilin, China.

Abstract:  Background and objective: MiR-658, paired box gene 3 (PAX3) and met proto-oncogene (MET) are overexpressed in gastric cancer while PAX3 and MET can be regulated by miRNA. Serum miR-658 may be associated with metastasis of gastric cancer (MGC) by affecting PAX3-MET pathway. Methods: Ninety-eight gastric carcinoma patients with distant MGC (DM group) and ninety-six gastric carcinoma patients with no MGC (NM group) were recruited. Serum miR-658 was validated between DM and NM groups by using quantitative reverse transcription PCR (qRT-PCR). PAX3 and MET levels were measured by Western Blot. The molecular mechanism for the function of serum miR-658 was further validated in gastric cell lines. Results: The results demonstrate that serum level of miR-658 is significantly lower in the NM group than in the DM group (P&lt; 0.001). Meanwhile, the levels of PAX3 and MET are lower in the NM group than in the DM group too (P&lt; 0.01). Both overexpression and silence of miR-658 significantly up-regulate or down-regulate the levels of PAX3 and MET in gastric cell lines (P&lt; 0.05). Conclusions: The present findings demonstrate that elevated circulating miR-658 is associated with MGC by activating PAX3-MET pathway. 

Retracted: No

PubPeer comments:
 The authors considers the notion of q-ROFNs and proposed a novel Euclidean distance measure between q-ROFNs in Section 2, which involves two different values of $q$. In eq.(5), the formula of the Euclidean distance is presented and corresponding properties are presented in Theorem 1. Consider $a_1 = (alpha_1, beta_1)$ as a 1-ROFN, i.e., $q_1 =1$, where $$(alpha_1, beta_1) = (.6, 0)$$ Therefore, according to eq.(2), $$gamma_1 = .4$$ Consider $a_2 = (alpha_2, beta_2)$ as a 2-ROFN, i.e., $q_2 =2$, where $$(alpha_2, beta_2) = (.6, 0)$$ Therefore, according to eq.(2), $$gamma_2 = .8$$ Then, according to eq.(5), $$d(a_1, a_2)  eq 0$$ It is not clear, by Theorem 1, which case of $a_1 = a_2$ or $a_1  eq a_2$ is true. Without clarifying this issue, the results presented in Table 1 are meaningless. ![file] ![file] Can the authors address this issue? , 
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 #2 Let $alpha_1$ be a 1-ROFN with $$alpha_1 = (0.5, 0.5)$$ and $alpha_2$ be a 2-ROFN with $$alpha_2 = (0.5+epsilon, 0.5)$$ Since according to eq.(5), only integer values are used for the value of $q$, so $alpha_2= (0.5+epsilon, 0.5)$ is considered as a 2-ROFN with $epsilon$ being a tiny positive number. Now $$q_1 = 1, quad q_2 =2$$ $$gamma_1 =1,quad gamma_2 = sqrt{1-(0.5+epsilon)^2 -(0.5)^2}$$ Then, according to eq.(5), $$d(alpha_1, alpha_2) = sqrt{frac{1}{2}bigg( (0.5^1 - (0.5+epsilon)^2)^2 +(0.5^1 -0.5^2)^2 + (1-(0.5+epsilon)^2 -0.5^2 )^2 bigg)}$$ Note that since $epsilon$ is tiny, $$d(alpha_1, alpha_2) approx 0.25times sqrt{3}$$ This seems not an acceptable answer. Correct me if I am wrong with the calculation. ,