Cancer is one of the most common public health complications worldwide and continues to capture great attention [1]. Colorectal cancer (CRC) represents one of the most common tumors and is one of the highest morbidity and mortality related cancers worldwide [2]. About 1.9 million patients were diagnosed with CRC in 2020, and an estimated 935,000 people died from the disease [3], [4]. In Egypt, CRC is the sixth most prevalent type of cancer and the eighth cause of cancer mortality [3]. The poor prognosis of CRC can be ascribed to inadequate early detection and efficacious therapy, in addition to the participation of unrecognizable molecular pathways [5].

Long non-coding RNAs (lncRNAs), a large constitute of noncoding RNA transcripts, are longer than 200 nucleotides [6]. LncRNAs can regulate gene expression at the transcriptional level and participate in the occurrence and development of different human diseases including cancer [7]. With the fast expansion of genome sequencing tools, lncRNAs have been conveyed to perform important functions in cancer related processes such as differentiation, cell proliferation, progression, and metastasis [8], [9].

Zinc finger NFX1-type containing 1(ZNFX1) antisense RNA 1 (ZFAS1), a lncRNA transcribed from the antisense orientation of ZNFX1, is located on chromosome 20q13.1 [10]. It was reported that, ZFAS1 may function as a regulatory player in many diseases, such as osteoarthritis, rheumatoid arthritis, acute myocardial infarction, epilepsy and cancers of the breast, lung and nasopharyngeal carcinoma [11], [12], [13], [14], [15], [16].

MicroRNAs (miRNAs, miRs) are short non-coding RNAs (∼22 nucleotides) that control gene translation by binding to the 3′ untranslated region of gene targeted messenger RNA [17]. miRNAs as a type of noncoding RNA that play crucial roles in various aspects of cancer development [18]. They have been suggested as potential targets for therapeutic interventions and as biomarkers for the early detection of tumors [19].

MicroRNA-200b is involved in the regulation of many tumor developments such as cell proliferation, reverse mesenchymal to epithelial transition (MET), cancer stem cell regulation, epithelial-to-mesenchymal transition (EMT), and drug resistance [20].

Zinc finger E-box binding homeobox 1 (ZEB1) is a key player regulator of the EMT, a phenomenon in which epithelial cells undergo a sequence of molecular alterations and exhibit specific traits of mesenchymal cells. [21]. ZEB1 has been identified as a fundamental gene involved in the process of EMT in various types of tumor, such as lung cancer, breast cancer, cervical cancer, and prostate cancer (PC) [22], [23], [24].

A previous study reported that the lncRNA ZFAS1/ miR200b/ ZEB1 protein axis can regulate EMT of CRC adenocarcinoma but their potential role as non-invasive diagnostic biomarkers for early stages CRC wasn’t evaluated [25].

This study aims to investigate the diagnostic utility of the lncRNA ZFAS1/ miR200b/ ZEB1 protein axis in early stages of CRC and the correlation of these biomarkers with each other.