Prognostic Significance of the Pluripotency Factors NANOG, SOX2, and OCT4 in Head and Neck Squamous Cell Carcinomas

Pedregal‐Mallo, Daniel; Hermida-Prado, Francisco; Granda-Díaz, Rocío; Montoro-Jiménez, Irene; Allonca, Eva; Pozo-Agundo, Esperanza; Álvarez-Fernández, Mónica; Álvarez-Marcos, César; García-Pedrero, Juana M.; Rodrigo, Juan P.

doi:10.3390/cancers12071794

Cited by 23 publications

(27 citation statements)

References 56 publications

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“…Cancer stem cells (CSCs) can affect tumor progression, recurrence, metastasis, and resistance to therapy [ 34 , 35 ], and there are many CSC markers, including OCT4 [ 36 ] and CD133 [ 37 ]. Chan et al suggested that CSCs can promote the progression of BLCA [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Prognosis-Related Risk Signature for Bladder Cancer to Predict Survival and Immune Landscapes

Wang

et al. 2021

Journal of Immunology Research

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Background. Bladder cancer is the tenth most common cancer worldwide. Valuable biomarkers in the field of diagnostic bladder cancer are urgently required. Method. Here, the gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA), GSE13507, GSE32894, and Mariathasan et al. Five prognostic genes were identified by the univariate, robust, and multivariate Cox’s regression and were used to develop a prognosis-related model. The Kaplan–Meier survival curves and receiver operating characteristics were used to evaluate the model’s effectiveness. The potential biological functions of the selected genes were analyzed using CIBERSORT and ESTIMATE algorithms. Cancer Therapeutics Response Portal (CTRP) and PRISM datasets were used to identify drugs with high sensitivity. Subsequently, using the bladder cancer (BLCA) cell lines, the role of TNFRSF14 was determined by Western blotting, cell proliferation assay, and 5-ethynyl-20-deoxyuridine assay. Results. GSDMB, CLEC2D, APOL2, TNFRSF14, and GBP2 were selected as prognostic genes in bladder cancer patients. The model’s irreplaceable reliability was validated by the training and validation cohorts. CD8+ T cells were highly infiltrated in the high-TNFRSF14-expression group, and M2 macrophages were the opposite. Higher expression of TNFRSF14 was associated with higher expression levels of LCK, interferon, MHC-I, and MHC-II, while risk score was the opposite. Many compounds with higher sensitivity for treating bladder cancer patients in the low-TNFRSF14-expression group were identified, with obatoclax being a potential drug most likely to treat patients in the low-TNFRSF14-expression group. Finally, the proliferation of BLCA cell lines was increased in the TNFRSF14-reduced group, and the differential expression was identified. TNFRSF14 plays a role in bladder cancer progression through the Wnt/β-catenin-dependent pathway. TNFRSF14 is a potential protective biomarker involved in cell proliferation in BLCA. Conclusion. We conducted a study to establish a 5-gene score model, providing reliable prediction for the outcome of bladder cancer patients and therapeutic drugs to individualize therapy. Our findings provide a signature that might help determine the optimal treatment for individual patients with bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of a Prognosis-Related Risk Signature for Bladder Cancer to Predict Survival and Immune Landscapes

Wang

et al. 2021

Journal of Immunology Research

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“…Other markers have emerged as potential prognostic factors, although their use has not yet entered the routine practice. NANOG and SOX2 protein expression is frequent in SCC; combined expression of both proteins showed the highest survival rates and double-negative cases the worst survival [ 28 ]. Moreover, markers such as cortactin (CTTN) and the focal adhesion kinase (FAK) and NANOG can be used as complementary markers for risk stratification in patients with laryngeal precancerous lesions [ 29 , 30 , 31 , 32 , 33 ].…”

Section: Qualitative Diagnosismentioning

confidence: 99%

Qualitative and Quantitative Diagnosis in Head and Neck Cancer

et al. 2021

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The diagnosis is the art of determining the nature of a disease, and an accurate diagnosis is the true cornerstone on which rational treatment should be built. Within the workflow in the management of head and neck tumours, there are different types of diagnosis. The purpose of this work is to point out the differences and the aims of the different types of diagnoses and to highlight their importance in the management of patients with head and neck tumours. Qualitative diagnosis is performed by a pathologist and is essential in determining the management and can provide guidance on prognosis. The evolution of immunohistochemistry and molecular biology techniques has made it possible to obtain more precise diagnoses and to identify prognostic markers and precision factors. Quantitative diagnosis is made by the radiologist and consists of identifying a mass lesion and the estimation of the tumour volume and extent using imaging techniques, such as CT, MRI, and PET. The distinction between the two types of diagnosis is clear, as the methodology is different. The accurate establishment of both diagnoses plays an essential role in treatment planning. Getting the right diagnosis is a key aspect of health care, and it provides an explanation of a patient’s health problem and informs subsequent decision. Deep learning and radiomics approaches hold promise for improving diagnosis.

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“…SOX2 is important in maintaining self-renewal and tumorigenesis and inhibiting differentiation in CSCs from melanoma, lung adenocarcinoma, and lymphoma tissue[ 62 - 64 ], and its elevated expression correlates positively with drug resistance and poor survival in prostate, breast, and glioma cancer patients[ 65 - 69 ]. Overexpression of NANOG in CSCs promotes tumorigenicity by regulating self-renewal and proliferation in prostate, ovarian, and head and neck squamous cells[ 4 , 70 - 72 ] and is an unfavorable prognostic marker in colorectal, renal, and rectal cancer patients[ 73 - 75 ]. KLF4 is a bifunctional transcription factor that can be an oncogenic or tumor suppressor signal, depending on the type of cancer[ 76 ]; lower KLF4 expression contributes to cellular hyperproliferation and malignant transformation in meningioma and prostate cancer[ 77 , 78 ], but upregulation of KLF4 promotes tumor progression in osteosarcoma, breast, and gastrointestinal cancer[ 79 - 81 ].…”

Section: Reporter Gene Systems To Study Cscsmentioning

confidence: 99%

“…Accordingly, CSCs can seed tumors when transplanted into immunocompromised or syngeneic animals. Also, CSCs mediate metastasis and the resistance to cytotoxic treatments, including radio- and chemotherapy, leading to minimal residual disease and cancer relapse[ 1 - 4 ].…”

Section: Introductionmentioning

confidence: 99%

Reporter gene systems for the identification and characterization of cancer stem cells

Salinas-Jazmín

Rosas-Cruz

Velasco-Velázquez

2021

WJSC

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Cancer stem cells (CSCs) are tumor cells that share functional characteristics with normal and embryonic stem cells. CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo- and radiotherapy, with important roles in tumor progression and the response to therapy. Thus, a current goal of cancer research is to eliminate CSCs, necessitating an adequate phenotypic and functional characterization of CSCs. Strategies have been developed to identify, enrich, and track CSCs, many of which distinguish CSCs by evaluating the expression of surface markers, the initiation of specific signaling pathways, and the activation of master transcription factors that control stemness in normal cells. We review and discuss the use of reporter gene systems for identifying CSCs. Reporters that are under the control of aldehyde dehydrogenase 1A1, CD133, Notch, Nanog homeobox, Sex-determining region Y-box 2, and POU class 5 homeobox can be used to identify CSCs in many tumor types, track cells in real time, and screen for drugs. Thus, reporter gene systems, in combination with in vitro and in vivo functional assays, can assess changes in the CSCs pool. We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics, demonstrating their value in CSCs research.

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Prognostic Significance of the Pluripotency Factors NANOG, SOX2, and OCT4 in Head and Neck Squamous Cell Carcinomas

Cited by 23 publications

References 56 publications

Identification of a Prognosis-Related Risk Signature for Bladder Cancer to Predict Survival and Immune Landscapes

Identification of a Prognosis-Related Risk Signature for Bladder Cancer to Predict Survival and Immune Landscapes

Qualitative and Quantitative Diagnosis in Head and Neck Cancer

Reporter gene systems for the identification and characterization of cancer stem cells

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