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Cancer Stem Cell Markers in Relation to Patient Survival Outcomes: Lessons for Integrative Diagnostics and
Kevin Dzobo1,2, Chelene Ganz1,2, Nicholas Ekow Thomford3,4
1International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa.
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.
Insights
Cancer stem cell (CSC) markers are often highly expressed in solid tumors like colon and lung cancers. However, individual CSC marker expression does not significantly predict patient survival, suggesting a need for integrated diagnostic approaches.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Diagnostics
Background:
- Solid tumors exhibit complex biology necessitating multifaceted treatment strategies.
- Current therapies often fail to prevent treatment resistance and relapse, largely by overlooking the tumor microenvironment (TME) and cancer stem cells (CSCs).
- CSCs are implicated in tumor initiation, progression, therapy resistance, and metastasis, making their markers potential diagnostic and therapeutic targets.
Purpose of the Study:
- To investigate the transcriptional expression and prognostic significance of various CSC markers in solid tumors.
- To compare CSC marker expression in tumor tissues versus adjacent normal tissues.
- To evaluate the potential of CSC markers as standalone predictors of overall patient survival.
Main Methods:
- Utilized publicly available databases: The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis.
- Examined and compared the transcriptional expression of 11 CSC markers (ABCB1, ABCG2, ALDH1A1, CD24, CD44, CD90, CD133, CXCR4, EPCAM, ICAM1, and NES).
- Analyzed marker expression in tumor tissues relative to adjacent normal tissues across multiple solid cancer types (colon, lung, pancreatic, esophageal).
Main Results:
- CSC markers were generally found to be expressed at higher levels in solid tumors compared to adjacent normal tissues.
- No single CSC marker exhibited a consistent expression pattern across all analyzed cancer types.
- Individual CSC marker expression, when analyzed in isolation, was not significantly associated with overall patient survival.
Conclusions:
- While CSC markers show differential expression in various solid tumors, their individual prognostic value is limited.
- Future innovations in cancer therapeutics and diagnostics should consider combinatorial CSC marker analysis.
- Integrative diagnostic approaches combining CSCs, TME components, and cancer cells are crucial for advancing cancer treatment and prognosis.
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