Emerging Role of NOTCH-related Long Non-coding RNA(s) as Biomarkers in Liquid Biopsy From Colorectal Cancer Patients

1. INTRODUCTION Background: Colorectal cancer (CRC) has been identified as a major public health concern given its high incidence and mortality rates (1). In 2020, CRC was the third-most prevalent malignancy after breast and lung cancer, accounting for 10% of new cases and ranking second in terms of mortality with 9.4% of deaths (2). Unfortunately, by year 2030, more than 2.2 million new cases and 1.1 million fatalities from CRC are globally anticipated (3).

Problem: Despite significant improvements in CRC surgical or radiological interventional treatment approaches with neo-adjuvant therapies, patients' prognosis remains bleak (4,5). Metastases and post-surgical tumor recurrence are prevalent, particularly, in more advanced cancer cases (6), which may account for the increased number of cases and fatalities prediction, being against the national efforts for achieving Egypt Vision 2030 implementing SDGs.

Problem statement: Conventionally used CRC prognostic markers for monitoring treatment outcome and pointing to cancer recurrence are carbohydrate antigen 19.9 (CA19.9) and/or carcinoembryonic antigen (CEA) that are not that sensitive (7) per patients subclassification or stratification related to CRC pathological characteristics for more efficient and earlier prognosis. Thence, a growing demand for sensitive and precise bio-molecular marker(s) better correlating with CRC prognostic markers and/or CRC clinical outcome (8), that is if successful would constitute the bases for "Better Health" SDG#3 and less cancer recurrence and, therefore, less mortality.

Liquid biopsies are used for cancer diagnosis or prognosis, like breast cancer, leukemia, liver cancer or CRC, via measurement of tumor-derived bio-molecular markers including circulating ncRNAs including long non-coding RNAs (lncRNAs), microRNA, exosomal ncRNAs, oncogenes or tumor suppressor genes, and their mutations, tumor-related-cytokines, and down-stream target proteins (9-22).

After extensive literature search and mining to mind-the-research-gap(s) for better "Cancer Epigenetics Study; a Step-toward ncRNA-Precision" we have chosen, in the current work, two notch-related lncRNAs to study in relation-to-CRC prognosis.