Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Hedegaard, Jakob; Lamy, Philippe; Nordentoft, Iver; Algaba, Ferrán; Høyer, Søren; Ulhøi, Benedicte Parm; Vang, Søren; Reinert, Thomas; Hermann, Gregers G.; Mogensen, Karin; Thomsen, Mathilde Borg Houlberg; Nielsen, Morten Muhlig; Márquez, Mirari; Segersten, Ulrika; Aine, Mattias; Höglund, Mattias; Birkenkamp‐Demtröder, Karin; Fristrup, Niels; Borre, Michael; Hartmann, Arndt; Stöhr, Robert; Wach, Sven; Keck, Bastian; Seitz, Anna Katharina; Nawroth, Roman; Maurer, Tobias; Tulić, C.; Simić, Tatjana; Junker, Kerstin; Horstmann, Marcus; Harving, Niels; Petersen, Astrid; Calle, M. Luz; Steyerberg, Ewout W.; Beukers, Willemien; Kessel, Kim E.M. van; Jensen, Jørgen Bjerggaard; Pedersen, Jakob Skou; Malmström, Per Uno; Malats, Núria; Real, Francisco X.; Zwarthoff, Ellen C.; Ørntoft, Torben F.; Dyrskjøt, Lars

doi:10.1016/j.ccell.2016.05.004

Cited by 492 publications

(592 citation statements)

References 54 publications

Supporting

Mentioning

545

Contrasting

Unclassified

Order By: Relevance

“…Differences in gender or smoking status do not influence the results [102]. Class 3 tumors show basal-like characteristics.…”

Section: Rna Messengermentioning

confidence: 73%

“…This study can be overlapped with other previous studies [105]. This kind of analysis could be a way for optimized surveillance programs and treatment selection [102].…”

Section: Rna Messengermentioning

confidence: 93%

“…They are mainly associated with repressed genes and with modifications of histones and/or chromatin. Class 1 tumors are characterized by a good prognosis, while class 2 shows poor prognosis and high expression of late cell-cycle genes, which have previously been associated with aggressiveness in bladder cancer [102,105,106]. Class 1 and class 2 tumors display different levels of aggressiveness.…”

Section: Rna Messengermentioning

confidence: 99%

“…They mapped sequences to the human genome and then explored the heterogeneity in early-stage bladder cancer of 8074 genes [102]. The results were interpreted by statistical analysis and, on the basis of these results; the bladder tumors were sub-grouped into three major classes [102][103][104]. They found that tumors of high stage and grade were more frequently observed in classes 2 and 3 than in class 1.…”

Section: Rna Messengermentioning

confidence: 99%

“…Hedegaard et al prepared a total RNA-sequencing (RNA-seq) libraries for 476 patients with bladder cancer at different stages (Ta, T1, in situ [CIS], MIBC). They mapped sequences to the human genome and then explored the heterogeneity in early-stage bladder cancer of 8074 genes [102]. The results were interpreted by statistical analysis and, on the basis of these results; the bladder tumors were sub-grouped into three major classes [102][103][104].…”

Section: Rna Messengermentioning

confidence: 99%

See 4 more Smart Citations

Bladder Cancer Markers and Recent Innovations

Viola-Magni¹,

Cataldi²,

Marocco³

2017

Bladder Cancer - Management of NMI and Muscle-Invasive Cancer

View full text Add to dashboard Cite

Bladder cancer (urothelial carcinoma) is the most common tumor of the urinary tract. It occurs more frequently among men about 65 years old on average. Two forms of the tumor are known: a non-muscle-invasive one and a muscle-invasive one. The latter turns out to be very aggressive with a survival of 5 years average. The non-muscle-invasive form frequently recurs (60-70%) and in 15% of cases, it progresses into the invasive form. The diagnosis is made mainly by cystoscopy and urine cytology. A high number of researches were dedicated in order to find a simple test using voided urine to frequently monitor possible tumor recurrence. During the last 10 years, many tests were proposed concerning either special proteins of which the most common are the bladder tumor antigen (BTA) and the nuclear matrix protein 22 (NMP22) or the presence of genetic mutations [most frequently, fibroblasts growth factor receptor 3 (FGFR3) and TP53], alteration of DNA methylation, chromatin structure and, more recently, the presence of specific micro-RNA. Recently the analysis of lipids present in voided urine showed a difference in fatty acids between healthy individuals and those affected by non-invasive forms. These markers appear to have a high specificity and sensitivity: a deepening of these results could lead to the development of a test that avoids invasive treatment and the cost of cystoscopy.

show abstract

“…Differences in gender or smoking status do not influence the results [102]. Class 3 tumors show basal-like characteristics.…”

Section: Rna Messengermentioning

confidence: 73%

“…This study can be overlapped with other previous studies [105]. This kind of analysis could be a way for optimized surveillance programs and treatment selection [102].…”

Section: Rna Messengermentioning

confidence: 93%

Section: Rna Messengermentioning

confidence: 99%

Section: Rna Messengermentioning

confidence: 99%

Section: Rna Messengermentioning

confidence: 99%

See 3 more Smart Citations

Bladder Cancer Markers and Recent Innovations

Viola-Magni¹,

Cataldi²,

Marocco³

2017

Bladder Cancer - Management of NMI and Muscle-Invasive Cancer

View full text Add to dashboard Cite

show abstract

Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient‐derived spheroid cultures

et al. 2017

Self Cite

View full text Add to dashboard Cite

Patient‐derived in vitro cultures of colorectal cancer (CRC) may help guide treatment strategies prior to patient treatment. However, most previous studies have been performed on a single biopsy per tumor. The purpose of this study was to analyze multiple spatially distinct biopsies from CRCs and see how well intratumor heterogeneity (ITH) was recapitulated in matching patient‐derived spheroids. Three to five biopsies were collected from six CRC tumors. Each biopsy was split in two; one half was used for spheroid culturing, while the other half was used for DNA and RNA purification. For two patients, lymph node metastases were analyzed. Somatic mutations were called from whole exome sequencing data. Each tumor contained mutations shared across all biopsies and spheroids, including major CRC drivers such as APC, KRAS, and TP53. At the same time, all tumors exhibited ITH on both mutation and copy number level. The concordance between biopsies and spheroids ranged between 40 and 70% for coding mutations. For three patients, the biopsy and spheroid from matching areas clustered together, meaning that the spheroid resembled the area of origin more than the other areas. However, all biopsies and spheroids contained private mutations. Therefore, multiple cultures from spatially distinct sites of the tumor increase the insight into the genetic profile of the entire tumor. Molecular subtypes were called from RNA sequencing data. When based on transcripts from both cancer and noncancerous cells, the subtypes were largely independent of sampling site. In contrast, subtyping based on cancer cell transcripts alone was dependent on sample site and genetic ITH. In conclusion, all examined CRC tumors showed genetic ITH. Spheroid cultures partly reflected this ITH, and having multiple cultures from distinct tumor sites improved the representation of the genetic tumor subclones. This should be taken into account when establishing patient‐derived models for drug screening.

show abstract

DRP1 contributes to head and neck cancer progression and induces glycolysis through modulated FOXM1/MMP12 axis

et al. 2022

View full text Add to dashboard Cite

Abnormal DRP1 expression has been identified in a variety of human cancers. However, the prognostic potential and mechanistic role of DRP1 in head and neck cancer (HNC) are currently poorly understood. Here, we demonstrated a significant upregulation of DRP1 in HNC tissues, and that DRP1 expression correlates with poor survival of HNC patients. Diminished DRP1 expression suppressed tumor growth and metastasis in both in vitro and in vivo models. DRP1 expression was positively correlated with FOXM1 and MMP12 expression in HNC patient samples, suggesting pathological relevance in the context of HNC development. Moreover, DRP1 depletion affected aerobic glycolysis through the downregulation of glycolytic genes, and overexpression of MMP12 in DRP1-depleted cells could help restore glucose consumption and lactate production. Using ChIP-qPCR, we showed that DRP1 modulates FOXM1 expression, which can enhance MMP12 transcription by binding to its promoter. We also showed that miR-575 could target 3'UTR of DRP1 mRNA and suppress DRP1 expression. Collectively, our study provides mechanistic insights into the role of DRP1 in HNC and highlights the potential of targeting the miR-575/DRP1/FOXM1/MMP12 axis as a novel therapy for the prevention of HNC progression.

show abstract

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Cited by 492 publications

References 54 publications

Bladder Cancer Markers and Recent Innovations

Bladder Cancer Markers and Recent Innovations

Characterization of genetic intratumor heterogeneity in colorectal cancer and matching patient‐derived spheroid cultures

DRP1 contributes to head and neck cancer progression and induces glycolysis through modulated FOXM1/MMP12 axis

Contact Info

Product

Resources

About