Cancer Stem Cells, CD44, and Outcomes Following Chemoradiation in Locally Advanced Cervical Cancer: Results From a Prospective Study

Chopra, Supriya; Deodhar, Kedar; Pai, V. R.; Pant, S.; Rathod, Nidul; Goda, Jayant Sastri; Sudhalkar, Niyati; Pandey, Puloma; Waghmare, Sanjeev K.; Engineer, Reena; Mahantshetty, Umesh; Ghosh, Jaya; Gupta, Sudeep; Shrivastava, Shyam K.

doi:10.1016/j.ijrobp.2018.09.003

Cited by 20 publications

(16 citation statements)

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“…The stem cell core transcription factor SOX2 is one of the stemness transcription factors, which can reprogram differentiated cells to stem cells [36]. SOX2 expression as well as expression of the other stem cell factors POU5F1 (also called Oct-4) and NANOG is associated with worse recurrence outcomes in localized cervical cancer patients treated with chemoradiation, suggesting that stemness is a resistance mechanism impeding treatment success in these patients [37]. SOX2 protein abundance derived from amplification of its locus is common in squamous carcinogenesis and is used clinically to confirm a squamous profile in evaluation of lung cancers [38].…”

Section: Discussionmentioning

confidence: 99%

3q26 Amplifications in Cervical Squamous Carcinomas

Voutsadakis

2021

Current Oncology

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Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.

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Section: Discussionmentioning

confidence: 99%

3q26 Amplifications in Cervical Squamous Carcinomas

Voutsadakis

2021

Current Oncology

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“…70 Squamous cancer of the cervix also expressed NANOG protein in 33% of patients; moderate to strong expression was detected in 24% of positive samples. 71…”

Section: Nanog In Cancermentioning

confidence: 99%

NANOG expression in human development and cancerogenesis

Grubelnik

Boštjančič

Pavlič

et al. 2020

Exp Biol Med (Maywood)

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NANOG is an important stem cell transcription factor involved in human development and cancerogenesis. Its expression is complex and regulated on different levels. Moreover, NANOG protein might regulate hundreds of target genes at the same time. NANOG is crucial for preimplantation development phase and progressively decreases during embryonic stem cells differentiation, thus regulating embryonic and fetal development. Postnatally, NANOG is undetectable or expressed in very low amounts in the majority of human tissues. NANOG re-expression can be detected during cancerogenesis, already in precancerous lesions, with increasing levels of NANOG in high grade dysplasia. NANOG is believed to enable cancer cells to obtain stem-cell like properties, which are believed to be the source of expanding growth, tumor maintenance, metastasis formation, and tumor relapse. High NANOG expression in cancer is frequently associated with advanced stage, poor differentiation, worse overall survival, and resistance to treatment, and is therefore a promising prognostic and predictive marker. We summarize the current knowledge on the role of NANOG in cancerogenesis and development, including our own experience. We provide a critical overview of NANOG as a prognostic and diagnostic factor, including problems regarding its regulation and detection. Impact statement NANOG has emerged as a key stem cell transcription factor in normal development and cancerogenesis. It is generally regarded as a good prognostic and predictive factor in various human cancers. It is less known that it is expressed already at precancerous stages in various organs, suggesting that finally an ideal candidate diagnostic marker has been discovered, enabling to distinguish between true dysplasia and reactive atypia. NANOG regulation is complex, and new insights into our understanding of its regulation might provide important information for future development in a broad field of two entirely different processes, i.e. normal development and cancerogenesis, showing how a physiologic mechanism can be used and abused, transforming itself into a key mechanism of disease development and progression.

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“…[14][15][16] High expression of podoplanin has been observed in various kinds of tumor cells, such as oral cancer, esophageal cancer, lung cancer, cervical cancer, renal cancer, and cutaneous basal cell carcinoma. [17][18][19] However, the function of podoplanin remains controversial in tumor cells. In most kinds of cancers, the podoplanin expression is associated with a higher carcinoma cell migration, leading to cancer metastasis, lower survival rates, and poor tumor stage.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Podoplanin in Various Tumors

Wang

Carvalho

Wang

et al. 2021

Technol Cancer Res Treat

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Background: The prognostic significance of podoplanin (PDPN) in tumor cells for cancer patients’ survival remains controversial. Therefore, we performed this meta-analysis to clarify the relationship between the podoplanin-positive tumor cells and cancer prognosis. Method: Eligible studies were identified by searching the Pubmed and EBSCO online databases up to August 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the correlation between podoplanin expression and overall survival (OS) and/or disease-free survival (DFS) and odds ratios (ORs) with 95% CIs severed as the summarized statistics for clinicopathological characteristic. Results: A total of 2155 patients from 21 eligible studies were included. The results revealed that high expression of podoplanin was associated with a poor survival rate in cancer patients. Further subgroup analysis stratified by tumor type showed that podoplanin-positive tumor cell infiltration had a negative prognostic effect associated with survival in esophageal cancer and oropharyngeal cancer. In addition, high expression of these cells was significantly associated with N stage, T stage, TNM stage and vascular invasion. Conclusion: Our study suggests the over-expression of podoplanin might be a significant prognostic indicator for patients with esophageal and oropharyngeal cancer.

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Cancer Stem Cells, CD44, and Outcomes Following Chemoradiation in Locally Advanced Cervical Cancer: Results From a Prospective Study

Cited by 20 publications

References 30 publications

3q26 Amplifications in Cervical Squamous Carcinomas

3q26 Amplifications in Cervical Squamous Carcinomas

NANOG expression in human development and cancerogenesis

Prognostic Value of Podoplanin in Various Tumors

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