A Novel Role For Nanog As An Early Cancer Risk Marker In Patients With Laryngeal Precancerous Lesions

Rodrigo, Juan P.; Villaronga, M. Ángeles; Menéndez, Sofía T.; Hermida-Prado, Francisco; Quer, Miquel; Vilaseca, Isabel; Allonca, Eva; Pedregal‐Mallo, Daniel; Astudillo, Aurora; García-Pedrero, Juana M.

doi:10.1038/s41598-017-11709-9

Cited by 30 publications

(36 citation statements)

References 19 publications

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“…We detected that NANOG is expressed in the cytoplasm of small intestinal cancer cells with and without nuclear accumulation, which corroborates the findings of other colorectal cancer studies [14,33]. This aberrant expression pattern is frequently found in a variety of cancers, with testicular germ cell tumors being a notable exception [34]. The regulation mechanism for localization is currently unknown and should be elucidated in the future.…”

Section: Discussionsupporting

confidence: 90%

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

Kim¹,

Chung²,

Ylaya³

et al. 2020

Preprint

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Background: The presence of KRAS mutation enhance the stem cell features of colorectal carcinoma cells containing mutant adenomatous polyposis coli (APC). However, their potential role in small intestinal adenocarcinoma remains elusive. Here, we aimed to investigate the clinical significance of cancer stem cell markers in the context of small intestinal adenocarcinoma with the KRAS genotype. Methods: SOX2, NANOG, and OCT4 expression were assessed by immunohistochemistry and digital image analysis, and their potential association with KRAS was further examined in 185 small intestinal adenocarcinoma patients. Results: Positive expression of SOX2, NANOG, and OCT4 was detected in 65 (35.1%), 94 (50.8%), and 82 (44.3%) of patients, respectively. SOX2-/wild-type KRAS (KRASWT) was often observed in low-grade carcinoma (P = 0.048). SOX2+ and SOX2+/mutant KRAS (KRASMT) were significantly associated with shorter overall survival relative to SOX2- and others (P < 0.001, both). Multivariate analysis revealed SOX2+ (HR=1.929 [95% CI, 1.320-2.819], P = 0.001) as an independent prognostic factor of worse overall survival among small intestinal adenocarcinoma patients. Conclusions: These results suggest that SOX2 expression, in conjunction with KRAS, is a potential prognostic marker for small intestinal adenocarcinoma.

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Section: Discussionsupporting

confidence: 90%

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

Kim¹,

Chung²,

Ylaya³

et al. 2020

Preprint

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“…Some studies indicate nuclear localization [56] ; others find only cytoplasmic staining [57] , [58] or both nuclear and cytoplasmic [59] . Cytoplasmic localization of NANOG was also described as a more significant early cancer risk factor than nuclear NANOG in patients with laryngeal precancerous lesions [60] .…”

Section: Discussionmentioning

confidence: 99%

Aggressive Phenotype of Cells Disseminated via Hematogenous and Lymphatic Route in Breast Cancer Patients

Markiewicz

Nagel

Szade

et al. 2018

Translational Oncology

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Intratumoral heterogeneity of breast cancer remains a major challenge in successful treatment. Failure of cancer therapies can also be accredited to inability to systemically eradicate cancer stem cells (CSCs). Recent evidence points to the role of epithelial-mesenchymal transition (EMT) in expanding the pool of tumor cells with CSCs features. Thus, we assessed expression level as well as heterogeneity of CSCs markers in primary tumors (PT), lymph node metastasis (LNM), and circulating tumor cells (CTCs)–enriched blood fractions in order to correlate them with signs of EMT activation as well as clinicopathological data of breast cancer patients. Level of CSCs markers (ALDH1, CD44, CD133, OCT-4, NANOG) and EMT markers was quantified in PT (N=107), LNM (N=56), and CTCs-enriched blood fractions (N=85). Heterogeneity of CSCs markers expression within each PT and LNM was assessed by calculating Gini Index. Percentage of ALDH1-positive cells was elevated in PT in comparison to LNM (P = .005). However, heterogeneity of the four CSCs markers: ALDH1 (P = .019), CD133 (P = .009), OCT-4 (P = .027), and CD44 (P < .001) was decreased in LNM. Samples classified as mesenchymal (post-EMT) showed elevated expression of CSCs markers (OCT-4 and CD44 in PT; OCT-4 in LNM; ALDH1, OCT-4, NANOG, CD44 in CTCs). Patients with mesenchymal-like CTCs had worse prognosis than patients with epithelial-like or no CTCs (P = .0025). CSCs markers are enriched in PT, LNM, and CTCs with mesenchymal features, but their heterogeneity is decreased in metastatic lymph nodes. Mesenchymal CTCs phenotype correlates with poor prognosis of the patients.

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“…Recently, researchers have shown increased expression levels of NANOGP8 in glioblastoma cancer stem cells and have suggested that NANOGP8 may participate in the reprogramming of normal cells into cancerous states [ 10 , 11 ]. Furthermore, various studies have also reported increased expression levels of NANOG in cancer stem cells in other types of cancers, such as breast and lung cancers, supporting that NANOG and NANOGP8 are established cancer markers [ 12 , 13 , 14 , 15 ]. Based on these findings, we analyzed the NANOG DNA sequence associated exosomes derived from a variety of cell sources to identify characteristics that could serve as diagnostic markers of cancer.…”

Section: Introductionmentioning

confidence: 92%

Differential sequences of exosomal NANOG DNA as a potential diagnostic cancer marker

2018

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NANOG has been demonstrated to play an essential role in the maintenance of embryonic stem cells, and its pseudogene, NANOGP8, is suggested to promote the cancer stem cell phenotype. As the roles of these genes are intimately involved with glioblastoma multiforme progression and exosomes are critical in intercellular communication, we conducted a detailed analysis of the association of the NANOG gene family with exosomes to identify diagnostic markers for cancer. Exosomes were precipitated from conditioned culture media from various cell lines, and NANOG gene fragments were directly amplified without DNA isolation using multiple primer sets. The use of the enzymes AlwNI and SmaI with restriction fragment length polymorphism analysis functioned to distinguish NANOGP8 from other NANOG family members. Collectively, results suggest that the NANOG DNA associated with exosomes is not full length and that mixed populations of the NANOG gene family exist. Furthermore, sequence analysis of exosomal DNA amplified with a NANOGP8 specific primer set frequently showed an insertion of a 22 bp sequence into the 3’ UTR. The occurrence rate of this insertion was significantly higher in exosomal DNA clones from cancer cells as compared to normal cells. We have detected mixed populations of NANOG DNA associated with exosomes and have identified preferential modulations in the sequences from cancer samples. Our findings, coupled with the properties of exosomes, may allow for the detection of traditionally inaccessible cancers (i.e. GBM) through minimally invasive techniques. Further analysis of exosomal DNA sequences of NANOG and other embryonic stemness genes (OCT3/4, SOX2, etc.) may establish a robust collection of exosome based diagnostic markers, and further elucidate the mechanisms of cancer formation, progression, and metastasis.

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A Novel Role For Nanog As An Early Cancer Risk Marker In Patients With Laryngeal Precancerous Lesions

Cited by 30 publications

References 19 publications

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

Prognostic implication of SOX2 expression in small intestinal adenocarcinoma

Aggressive Phenotype of Cells Disseminated via Hematogenous and Lymphatic Route in Breast Cancer Patients

Differential sequences of exosomal NANOG DNA as a potential diagnostic cancer marker

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