Abstract
Solid tumors display a complex biology that requires a multipronged treatment strategy. Most anticancer interventions, including chemotherapy, are currently unable to prevent treatment resistance and relapse. In general, therapeutics target cancer cells and overlook the tumor microenvironment (TME) and the presence of cancer stem cells (CSCs) with self-renewal and tumorigenic abilities. CSCs have been postulated to play key roles in tumor initiation, progression, therapy resistance, and metastasis. Hence, CSC markers have been suggested as diagnostics to forecast cancer prognosis as well as molecular targets for new-generation cancer treatments, especially in resistant disease. We report here original findings on expression and prognostic significance of CSC markers in several cancers. We examined and compared the transcriptional expression of CSC markers (ABCB1, ABCG2, ALDH1A1, CD24, CD44, CD90, CD133, CXCR4, EPCAM, ICAM1, and NES) in tumor tissues versus the adjacent normal tissues using publicly available databases, The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis. We found that CSC transcriptional markers were, to a large extent, expressed in higher abundance in solid tumors such as colon, lung, pancreatic, and esophageal cancers. On the other hand, no CSC marker in our analysis was expressed in the same pattern in all cancers, while individual CSC marker expression, alone, was not significantly associated with overall patient survival. Innovation in next-generation cancer therapeutics and diagnostics ought to combine CSC markers as well as integrative diagnostics that pool knowledge from CSCs and other TME components and cancer cells.
Highlights
Huge progress has been made in the treatment of cancer but its health burden continues to increase globally, raising the need for novel therapeutic strategies to contain cancer [1, 2]
Bioinformatic analysis showed that cancer stem cells (CSCs) markers, CD24, cluster of differentiation 44 (CD44), CD90 and CD133 expression was significantly enhanced in colon adenocarcinoma (COAD) compared to adjacent normal tissues (Figure 1)
Another CSC marker, aldehyde dehydrogenase 1 (ALDH1) expression was significantly reduced in tumor samples versus normal samples (Figure 1)
Summary
Huge progress has been made in the treatment of cancer but its health burden continues to increase globally, raising the need for novel therapeutic strategies to contain cancer [1, 2]. Many times the utilisation of these clinical factors is not enough for risk stratification and prediction of disease outcome. For many cancers, including those that are not well studied such as esophageal cancer, there is an urgent need for the identification of reliable prognostic factors that can accurately predict clinical prognosis. Several recent studies have revealed that a major mechanism for post-therapeutic recurrence and metastasis of cancers is the presence of therapy-resistant cancer stem cells [5, 6, 29,30,31]. It has been demonstrated that chemoresistance to 5-fluorouracil and cisplatin in several cancer patients may occur through the increased expression of microRNAs such as miR-200 and cancer stem cell-related proteins [32, 33]. Increased expression of the multidrug resistance doi:10.20944/preprints202005.0047.v1 protein 2 (MRP2) has been shown in the tissue samples of patients resistant to neo-adjuvant chemotherapy including 5-fluorouracil, doxorubicin and cisplatin [34,35,36]
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