Increased expression of Psoriasin is correlated with poor prognosis of bladder transitional cell carcinoma by promoting invasion and proliferation

Liu, Jia; Zhao, Zehang; Sun, Zhiwei; Liu, Chang; Cheng, Xiaoxing; Ruge, Fiona; Yang, Yong; Jiang, Wen Guo; Ye, Lin

doi:10.3892/or.2019.7445

Cited by 5 publications

(8 citation statements)

References 29 publications

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“…Upregulation of calcium-sensing proteins CALML3, CALML5 and S100A7A was also noted in 'non-responders'. Previously, a correlation of S100A7A (also known as psoriasin) expression with poor bladder cancer survival was seen [37]. A role for other S100 family of calcium-binding proteins in bladder cancer cisplatin sensitivity has also been reported [38,39].…”

Section: Discussionmentioning

confidence: 94%

Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Hepburn

Lazzarini

Veeratterapillay

et al. 2021

Cancers

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Cisplatin-based neoadjuvant chemotherapy (NAC) is recommended prior to radical cystectomy for muscle-invasive bladder cancer (MIBC) patients. Despite a 5–10% survival benefit, some patients do not respond and experience substantial toxicity and delay in surgery. To date, there are no clinically approved biomarkers predictive of response to NAC and their identification is urgently required for more precise delivery of care. To address this issue, a multi-methods analysis approach of machine learning and differential gene expression analysis was undertaken on a cohort of 30 MIBC cases highly selected for an exquisitely strong response to NAC or marked resistance and/or progression (discovery cohort). RGIFE (ranked guided iterative feature elimination) machine learning algorithm, previously demonstrated to have the ability to select biomarkers with high predictive power, identified a 9-gene signature (CNGB1, GGH, HIST1H4F, IDO1, KIF5A, MRPL4, NCDN, PRRT3, SLC35B3) able to select responders from non-responders with 100% predictive accuracy. This novel signature correlated with overall survival in meta-analysis performed using published NAC treated-MIBC microarray data (validation cohort 1, n = 26, Log rank test, p = 0.02). Corroboration with differential gene expression analysis revealed cyclic nucleotide-gated channel, CNGB1, as the top ranked upregulated gene in non-responders to NAC. A higher CNGB1 immunostaining score was seen in non-responders in tissue microarray analysis of the discovery cohort (n = 30, p = 0.02). Kaplan-Meier analysis of a further cohort of MIBC patients (validation cohort 2, n = 99) demonstrated that a high level of CNGB1 expression associated with shorter cancer specific survival (p < 0.001). Finally, in vitro studies showed siRNA-mediated CNGB1 knockdown enhanced cisplatin sensitivity of MIBC cell lines, J82 and 253JB-V. Overall, these data reveal a novel signature gene set and CNGB1 as a simpler proxy as a promising biomarker to predict chemoresponsiveness of MIBC patients.

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Section: Discussionmentioning

confidence: 94%

Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Hepburn

Lazzarini

Veeratterapillay

et al. 2021

Cancers

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“…Nevertheless, increased expression of S100A7 protein has been described in various cancer types (e.g. breast, bladder and head and neck carcinomas) and often with a correlation to poor clinical outcome (9)(10)(11)(12)(13)(14)20). In addition, S100A7 has been shown to be functionally linked to oncogenic properties in oral SCCs, as depletion of this gene inhibited cell growth, invasion and migration (21).…”

Section: Discussionmentioning

confidence: 99%

“…A handful of these prognostic studies have utilized IHC to quantify psoriasin expression. However, different quantification approaches and different cut-off levels for psoriasin expression have been used ( 10 , 14 , 15 ). For this reason, we here applied a cut-off value previously used in HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…cell survival and maturation. Increased expression of the protein has been reported in malignant and premalignant lesions and overexpression has also been correlated with clinical outcome (9)(10)(11)(12)(13)(14). In a previous study by Tripathi et al (15), the expression of psoriasin was correlated to a worse prognosis in patients with head and neck carcinomas (HNSCC), but neither HPV status nor sub-site was considered in that study.…”

Section: Introductionmentioning

confidence: 94%

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Psoriasin expression is associated with survival in patients with human papillomavirus-positive base of tongue squamous cell carcinoma

et al. 2021

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Patients with human papillomavirus-positive (HPV+) base of tongue squamous cell carcinomas (BOTSCC) have an improved survival compared with patients with HPV-negative BOTSCC and it has been suggested that treatment should be tailored. Before individualized treatment can be introduced, additional prognostic markers are required. A prognostic role of psoriasin has previously been demonstrated outside BOTSCC. Therefore, the present study aimed to examine psoriasin in BOTSCC, with focus on HPV+ BOTSCC, in relation to prognosis. A total of 72 BOTSCC samples were stained for psoriasin by immunohistochemistry, and the association between expression and clinical outcomes was analyzed. Patients with low psoriasin expression exhibited significantly improved overall survival (OS; P=0.001) and disease-free survival (DFS; P=0.007), which also was observed in patients with HPV+ BOTSCC (OS, P<0.001; DFS, P= 0.02). Furthermore, psoriasin was a significant prognostic factor in univariable and multivariable analyses. In conclusion, psoriasin could be used as a prognostic marker in HPV+ BOTSCC.

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“…S100 family members are involved in a plethora of cellular processes including proliferation, differentiation, inflammation and apoptosis 55 . Altered S100A7 expression has been linked to poor clinical outcomes in several solid cancer types by promoting invasiveness of cancer cells via upregulation of MMPs 56 . Moreover, S100A2 is a crucial factor for proliferation and differentiation of epithelial cells 57 and promoting neoplastic transformation 19 .…”

Section: Discussionmentioning

confidence: 99%

MACE RNA sequencing analysis of conjunctival squamous cell carcinoma and papilloma using formalin-fixed paraffin-embedded tumor tissue

Boneva

Schlecht

Zhang

et al. 2020

Sci Rep

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Recent advances in the field of biomedical research allow for elucidation of the transcriptional signature of rare tumors such as conjunctival squamous cell carcinoma (SCC). In this study we compare its expression profile to conjunctival papilloma (Pap) and healthy conjunctival tissue (Ctrl) and develop a classification tool to differentiate these entities. Seven conjunctival SCC, seven Pap and ten Ctrl were formalin-fixed and paraffin-embedded (FFPE) and analyzed using Massive Analysis of cDNA Ends (MACE) RNA sequencing. Differentially expressed genes (DEG) and gene ontology (GO) clusters were explored and the abundance of involved cell types was quantified by xCell. Finally, a classification model was developed to distinguish SCC from Pap and Ctrl. Among the most prominent DEG in SCC a plethora of keratins were upregulated when compared to Pap and Ctrl. xCell analysis revealed an enrichment of immune cells, including activated dendritic cells and T-helper type 1 cells (Th1), in SCC when compared to Ctrl. The generated classification model could reliably discriminate between the three entities according to the expression pattern of 30 factors. This study provides a transcriptome-wide gene expression profile of rare conjunctival SCC. The analysis identifies distinct keratins, as well as dendritic and Th1 cells as important mediators in SCC. Finally, the provided gene expression classifier may become an aid to the conventional histological classification of conjunctival tumors in uncertain cases.

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Increased expression of Psoriasin is correlated with poor prognosis of bladder transitional cell carcinoma by promoting invasion and proliferation

Cited by 5 publications

References 29 publications

Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Identification of CNGB1 as a Predictor of Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Psoriasin expression is associated with survival in patients with human papillomavirus-positive base of tongue squamous cell carcinoma

MACE RNA sequencing analysis of conjunctival squamous cell carcinoma and papilloma using formalin-fixed paraffin-embedded tumor tissue

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