BACKGROUND Feed-forward loops (FFLs), consisting of miRNAs, transcription factors (TFs) and their common target genes, have been validated to be important for the initialization and development of complex diseases, including cancer. Esophageal Carcinoma (ESCA) and Stomach Adenocarcinoma (STAD) are two types of malignant tumors in the digestive tract. Understanding common and distinct molecular mechanisms of ESCA and STAD is extremely crucial. RESULTS In this paper, we presented a computational framework to explore common and distinct FFLs, and molecular biomarkers for ESCA and STAD. We identified FFLs by combining regulation pairs and RNA-seq data. Then we constructed disease-specific co-expression networks based on the FFLs identified. We also used random walk with restart (RWR) on disease-specific co-expression networks to prioritize candidate molecules. We identified 148 and 242 FFLs for these two types of cancer, respectively. And we found that one TF, E2F3 was related to ESCA, two genes, DTNA and KCNMA1 were related to STAD, while one TF ESR1 and one gene KIT were associated with both of the two types of cancer. CONCLUSIONS This proposed computational framework predicted disease-related biomolecules effectively and discovered the correlation between two types of cancers, which helped develop the diagnostic and therapeutic strategies of Esophageal Carcinoma and Stomach Adenocarcinoma.

中文翻译：

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食管癌和胃腺癌中疾病特异性基因调控网络的探索。

背景技术由miRNA，转录因子（TF）及其共同的靶基因组成的前馈环（FFL）已被证实对于包括癌症在内的复杂疾病的初始化和发展具有重要意义。食道癌（ESCA）和胃腺癌（STAD）是消化道中的两种恶性肿瘤。了解ESCA和STAD的共同而独特的分子机制极为重要。结果在本文中，我们提出了一个计算框架，以探索常见和不同的FFL，以及ESCA和STAD的分子生物标记。我们通过结合调控对和RNA-seq数据鉴定了FFL。然后，我们基于已识别的FFL构建了特定于疾病的共表达网络。我们还对特定疾病的共表达网络使用了随机重启步行（RWR）来对候选分子进行优先排序。我们分别针对这两种类型的癌症确定了148和242个FFL。我们发现一种TF，E2F3与ESCA相关，两种基因DTNA和KCNMA1与STAD相关，而一种TF ESR1和一种基因KIT与两种类型的癌症都相关。结论该拟议的计算框架有效地预测了与疾病有关的生物分子，并发现了两种癌症之间的相关性，这有助于发展食管癌和胃腺癌的诊断和治疗策略。而一种TF ESR1和一种基因KIT与两种类型的癌症都相关。结论该拟议的计算框架有效地预测了与疾病有关的生物分子，并发现了两种癌症之间的相关性，这有助于发展食管癌和胃腺癌的诊断和治疗策略。而一种TF ESR1和一种基因KIT与两种类型的癌症都相关。结论该拟议的计算框架有效地预测了与疾病有关的生物分子，并发现了两种癌症之间的相关性，这有助于发展食管癌和胃腺癌的诊断和治疗策略。