This paper presents a consensus-based approach that incorporates three microarray and three RNA-Seq methods for unbiased and integrative identification of differentially expressed genes (DEGs) as potential biomarkers for critical disease(s). The proposed method performs satisfactorily on two microarray datasets (GSE20347 and GSE23400) and one RNA-Seq dataset (GSE130078) for esophageal squamous cell carcinoma (ESCC). Based on the input dataset, our framework employs specific DE methods to detect DEGs independently. A consensus based function that first considers DEGs common to all three methods for further downstream analysis has been introduced. The consensus function employs other parameters to overcome information loss. Differential co-expression (DCE) and preservation analysis of DEGs facilitates the study of behavioral changes in interactions among DEGs under normal and diseased circumstances. Considering hub genes in biologically relevant modules and most GO and pathway enriched DEGs as candidates for potential biomarkers of ESCC, we perform further validation through biological analysis as well as literature evidence. We have identified 25 DEGs that have strong biological relevance to their respective datasets and have previous literature establishing them as potential biomarkers for ESCC. We have further identified 8 additional DEGs as probable potential biomarkers for ESCC, but recommend further in-depth analysis.