Cancer stem cells enrichment with surface markers CD271 and CD44 in human head and neck squamous cell carcinomas

Elkashty, Osama A.; Elghanam, Ghada Abu; Su, Xiu; Liu, Younan; Chauvin, Peter J.; Tran, Simon D.

doi:10.1093/carcin/bgz182

Cited by 48 publications

(51 citation statements)

References 53 publications

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“…CD271, a receptor for nerve growth factor has a greater capacity of tumor initiation. CD271 + CD44 + subpopulation reported to contain the more stem cell like cells having an enhanced tumorigenic, proliferative and metastatic potential [38][39][40][41] CD271 has dual role being proliferative to stimulate survival or anti-proliferative to stimulate cell death [32,42]. In this study the expression of CD271 was investigated in breast cancer patients along with cancer stem cells (MCF7-CSCs) to de ne its role as proliferative or anti-proliferative.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of CD271 Transcriptome in Breast Cancer Promotes Cell Survival via NFκB Pathway

Shahid

Bashir

Ishfaq

et al. 2021

Preprint

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BackgroundBiological treatment of many cancers currently targets membrane bound receptors located on a cell surface. We are in a great to need identify novel membrane proteins associated with migration and metastasis of breast cancer cells. CD271, a single transmembrane protein belongs to tumor necrosis factor receptor acts and play its role in proliferation of cancer cell. The purpose of this study is to investigate the role of CD271 in breast cancer. Methods and ResultsIn this study we analyzed the expression of CD271 in breast tumor tissue, breast cancer cell line MCF7 and isolated cancer stem cells (MCF7-CSCs) by quantitative real-time polymerase chain reaction (RT-qPCR). CD271 was upregulated among breast cancer patients in all age groups. Within the promoter region of CD271, there is a binding site for NF-κB1 which overlaps a putative quadraplex forming sequence. While CD271 also activates NF-κB pathway, down regulation of CD271 through quadraplex targeting resulted in inhibition of NF-κB and its downstream targets Nanog and Sox2ConclusionIn conclusion, CD271 and NF-κB are interrelated to each other. Upon CD271 inhibition, the NF-κB expression also reduces which then effected the cell proliferation and migration. These results suggest that NF-κB is regulated by CD271 is playing a crucial role in cancer development and could be a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Upregulation of CD271 Transcriptome in Breast Cancer Promotes Cell Survival via NFκB Pathway

Shahid

Bashir

Ishfaq

et al. 2021

Preprint

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“…HNSCC is a kind of squamous cell carcinoma that occurs in the mouth, oropharynx, hypopharynx and throat, 17,18 the 5‐year survival rate of which is still less than 50% 19,20 . CSCs are a few cells with self‐renewal and unlimited proliferation potential in tumor tissues, which are closely related to the formation and development of HNSCC 21 . At present, it is believed that the traditional treatment can only remove the non‐stem cell components in the tumor, but not effectively kill CSCs, which is the driving factor of tumor recurrence 21 .…”

Section: Discussionmentioning

confidence: 99%

“…CSCs are a few cells with self‐renewal and unlimited proliferation potential in tumor tissues, which are closely related to the formation and development of HNSCC 21 . At present, it is believed that the traditional treatment can only remove the non‐stem cell components in the tumor, but not effectively kill CSCs, which is the driving factor of tumor recurrence 21 . Therefore, the therapeutic mode targeting CSCs has great potential in clinical application.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes associated with cancer stem cell characteristics in head and neck squamous cell carcinoma through co‐expression network analysis

et al. 2020

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Background Head and neck squamous cell carcinoma (HNSCC) is a type of invasive malignancy and the seventh most common cancer in the worldwide. Cancer stem cells (CSCs) are self‐renewal cells in tumors and can produce heterogeneous tumor cells, which play an important role in the development of HNSCC. In our research, we aimed to identify genes related to the CSCs characteristics in HNSCC. Methods Messenger RNA (mRNA) expression‐based stiffness index (mRNAsi) can be used as a quantitative characterization of CSCs. We used one‐class logistic regression machine learning algorithm (OCLR) to calculate the mRNAsi and investigate the relationship between mRNAsi and clinical characteristics of HNSCC. Then, a weighted gene co‐expression network analysis (WGCNA) and protein‐protein interaction (PPI) network was constructed to screen hub genes related to mRNAsi of HNSCC. Results The results indicated that the score of mRNAsi in HNSCC tissues is higher than in paracancer tissues, while the mRNAsi was not statistically correlated with the prognosis and clinical characteristics of HNSCC. Six positive and six negative hub genes related to mRNAsi of HNSCC were selected, which may act as therapeutic targets for inhibiting CSCs within HNSCC. Conclusions In conclusion, our research selected 12 hub genes related to mRNAsi of HNSCC through weighted gene co‐expression network analysis. These genes may become therapeutic targets to inhibit the CSCs of HNSCC in the future.

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“…Another female specific DEG is the MHC class II gene HLA-DRA, which was specifically downregulated [26]. Male-specific DEGs include MCM7, a DNA replication licensing factor [17]; NKX2-2, an important biomarker for metastatic prostate cancers [27]; and NGFR, the canonical single-pass transmembrane receptor linked to melanoma [28] and squamous cell carcinoma [29].…”

Section: Magec3 Expression Associates With Different Genes Depending On Sexmentioning

confidence: 99%

MAGEC3 is a prognostic biomarker in ovarian and kidney cancers

Ellegate

Mastri

Isenhart

et al. 2021

Preprint

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Rare variants in MAGEC3, members of the melanoma antigen gene family, are associated with BRCA-independent early onset ovarian cancers, while somatic mutations of this gene have been associated with kidney cancers. In this report, we quantified normal and tumor protein expression of MAGEC3 via immunohistochemistry in N=394 ovarian cancers and N=220 renal cell carcinomas. MAGEC3 protein levels fell into two categories – normal MAGEC3 and MAGEC3 loss – characterized by expression equivalent to normal tissue or significantly lower than normal tissue, respectively. Interestingly, cases with MAGEC3 loss demonstrated better overall survival in both ovarian cancers and renal cell carcinomas, which resembles patient outcomes with BRCA2 loss. MAGEC3 protein expression was associated with upregulation of pathways regulating G2/M checkpoint (NES: 4.13, FDR<0.001) and mitotic spindle formation (NES: 2.84, FDR<0.001). Increased CD8+ cell infiltration, coordinate expression of other cancer testis antigens, and tumor mutational burden were also associated with MAGEC3 expression. To emphasize the impact of these results, we built a prognostic RNA-based model using N=180 cancers of an independent cohort with matching transcriptomic data and tested its performance in two large public cohorts (N=282 ovary and N=606 kidney). Results based on predicted protein scores within these patients validated those discovered in patients with directly measured MAGEC3 protein. The RNA model was reproduced in independent cohorts implying a broader potential for MAGEC3-driven disease etiology and relevance to potential treatment selection.STATEMENT OF TRANSLATIONAL RELEVANCEMAGEC3 protein is expressed in multiple tissues and is dysregulated in cancer. In this work, we show that ovarian and kidney cancer patients with loss of MAGEC3 protein have favorable prognosis, indicating that MAGEC3 protein level may be used as a prognostic biomarker. Integrative genomic analysis of patients spanning more than nine cancer types showed an association between MAGEC3 protein and genes affecting stress response, including those involved in cell cycle and DNA damage repair. Additionally, it is correlated with tumor mutational burden in patients with mutated oncogenes. These associations suggest that MAGEC3 protein levels may be used to identify patients with deficient DNA damage repair mechanisms that can be targeted by PARP inhibitors. To operationalize this idea, we use machine learning to predict MAGEC3 protein levels from RNA sequencing data which can facilitate the identification of patients for treatment stratification according to their MAGEC3 status.

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Cancer stem cells enrichment with surface markers CD271 and CD44 in human head and neck squamous cell carcinomas

Cited by 48 publications

References 53 publications

Upregulation of CD271 Transcriptome in Breast Cancer Promotes Cell Survival via NFκB Pathway

Upregulation of CD271 Transcriptome in Breast Cancer Promotes Cell Survival via NFκB Pathway

Identification of genes associated with cancer stem cell characteristics in head and neck squamous cell carcinoma through co‐expression network analysis

MAGEC3 is a prognostic biomarker in ovarian and kidney cancers

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