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Insights into Urologic Cancer

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 28765

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Special Issue Editors

Dr. Jörg Ellinger

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Guest Editor

University Hospital Bonn, Clinic for Urology and Pediatric Urology, Bonn, Germany
Interests: urological oncology; renal cell carcinoma; epigenetics; biomarker

Dr. Niklas Klümper

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Guest Editor

University Hospital Bonn, Clinic for Urology and Pediatric Urology, Bonn, Germany
Interests: urological oncology; immuno-oncology; renal cell carcinoma

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit a manuscript to the Special Issue “Insights into Urological Cancer”. Urological malignancies account for a fifth of newly diagnosed cancers in Western countries. Despite advances in medical tumor therapy, metastatic disease is a common cause of death in patients with a prostate, bladder, or kidney cancer. The development of new therapeutic approaches enables a better understanding of molecular changes in urological tumors. In addition, molecular stratification is necessary to achieve individualized therapies in the future.

This Special Issue of Cancers, therefore, welcomes original research articles and reviews related to urological malignancies.

We look forward to receiving your contributions.

Dr. Jörg Ellinger
Dr. Niklas Klümper
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

prostate cancer
bladder cancer
renal cell carcinoma
testicular cancer
carcinogenesis
immune checkpoint inhibition
immunotherapy
biomarker
early diagnosis
epigenetics
genomics
transcriptomics

Published Papers (14 papers)

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Editorial

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4 pages, 194 KiB

Open AccessEditorial

Insights into Urologic Cancer

by Niklas Klümper and Jörg Ellinger

Cancers 2023, 15(12), 3108; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123108 - 08 Jun 2023

Viewed by 678

Abstract

Collectively, urological malignancies account for a considerable proportion of cancer cases worldwide [...] Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

Research

Jump to: Editorial

14 pages, 2474 KiB

Open AccessArticle

Patient’s Desire and Real Availability Concerning Supportive Measures Accompanying Radical Prostatectomy: Differences between Certified Prostate Cancer Centers and Non-Certified Centers Based on Patient-Reported Outcomes within the Cross-Sectional Study Improve

by Ingmar Wolff, Martin Burchardt, Julia Peter, Christian Thomas, Danijel Sikic, Christian Fiebig, Sören Promnitz, Bernd Hoschke, Maximilian Burger, Marco J. Schnabel, Christian Gilfrich, Niklas Löbig, Nina N. Harke, Florian A. Distler and Matthias May

Cancers 2023, 15(10), 2830; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15102830 - 19 May 2023

Cited by 4 | Viewed by 1087

Abstract

Certification as a prostate cancer center requires the offer of several supportive measures to patients undergoing radical prostatectomy (RP). However, it remains unclear how patients estimate the relevance of these measures and whether the availability of these measures differs between certified prostate cancer centers (CERTs) and non-certified centers (NCERTs). In 20 German urologic centers, a survey comprising questions on the relevance of 15 supportive measures was sent to 1000 patients at a median of 15 months after RP. Additionally, patients were asked to rate the availability of these measures using a four-item Likert scale. The aim of this study was to compare these ratings between CERTs and NCERTs. The response rate was 75.0%. In total, 480 patients underwent surgery in CERTs, and 270 in NCERTs. Patients rated 6/15 supportive measures as very relevant: preoperative medical counselling concerning treatment options, a preoperative briefing answering last questions, preoperative pelvic floor exercises (PFEs), postoperative PFEs, postoperative social support, and postoperative rehabilitation addressing physical fitness recovery. These ratings showed no significant difference between CERTs and NCERTs (p = 0.133–0.676). In addition, 4/9 of the remaining criteria were rated as more detailed by patients in CERTs. IMPROVE represents the first study worldwide to evaluate a patient-reported assessment of the supportive measures accompanying RP. Pertinent offers vary marginally between CERTs and NCERTs. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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18 pages, 6460 KiB

Open AccessArticle

Altered Plasma, Urine, and Tissue Profiles of Sulfatides and Sphingomyelins in Patients with Renal Cell Carcinoma

by Robert Jirásko, Jakub Idkowiak, Denise Wolrab, Aleš Kvasnička, David Friedecký, Krzysztof Polański, Hana Študentová, Vladimír Študent, Bohuslav Melichar and Michal Holčapek

Cancers 2022, 14(19), 4622; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194622 - 23 Sep 2022

Cited by 7 | Viewed by 2586

Abstract

Purpose: RCC, the most common type of kidney cancer, is associated with high mortality. A non-invasive diagnostic test remains unavailable due to the lack of RCC-specific biomarkers in body fluids. We have previously described a significantly altered profile of sulfatides in RCC tumor tissues, motivating us to investigate whether these alterations are reflected in collectible body fluids and whether they can enable RCC detection. Methods: We collected and further analyzed 143 plasma, 100 urine, and 154 tissue samples from 155 kidney cancer patients, together with 207 plasma and 70 urine samples from 214 healthy controls. Results: For the first time, we show elevated concentrations of lactosylsulfatides and decreased levels of sulfatides with hydroxylated fatty acyls in body fluids of RCC patients compared to controls. These alterations are emphasized in patients with the advanced tumor stage. Classification models are able to distinguish between controls and patients with RCC. In the case of all plasma samples, the AUC for the testing set was 0.903 (0.844–0.954), while for urine samples it was 0.867 (0.763–0.953). The models are able to efficiently detect patients with early- and late-stage RCC based on plasma samples as well. The test set sensitivities were 80.6% and 90%, and AUC values were 0.899 (0.832–0.952) and 0.981 (0.956–0.998), respectively. Conclusion: Similar trends in body fluids and tissues indicate that RCC influences lipid metabolism, and highlight the potential of the studied lipids for minimally-invasive cancer detection, including patients with early tumor stages, as demonstrated by the predictive ability of the applied classification models. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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12 pages, 1554 KiB

Open AccessFeature PaperArticle

Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value—Need for Biomarker Testing in High-Risk Patients?

by Severin Rodler, Lennert Eismann, Boris Schlenker, Jozefina Casuscelli, Isabel Brinkmann, Andrea Sendelhofert, Raphaela Waidelich, Alexander Buchner, Christian Stief, Gerald Bastian Schulz and Stephan Ledderose

Cancers 2022, 14(18), 4411; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184411 - 11 Sep 2022

Cited by 10 | Viewed by 2722

Abstract

Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody–drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan–Meier method. Median expression of Nectin-4 was 150 (range 0–250) in SCC, 140.5 (range 30–275) in ADENO, and 10 (0–185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (p < 0.001). For SCC, ADENO or SARCO no differences regarding OS or PFS were observed based on Nectin-4 expression levels (p > 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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23 pages, 7646 KiB

Open AccessArticle

NXPH4 Promotes Gemcitabine Resistance in Bladder Cancer by Enhancing Reactive Oxygen Species and Glycolysis Activation through Modulating NDUFA4L2

by Decai Wang, Pu Zhang, Zijian Liu, Yifei Xing' and Yajun Xiao

Cancers 2022, 14(15), 3782; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153782 - 03 Aug 2022

Cited by 6 | Viewed by 2272

Abstract

Bladder cancer is one of the most prevalent kinds of cancer worldwide, and resistance to gemcitabine is a major problem for patients. The pathogenesis of bladder cancer and mechanism of resistance to chemotherapy remain to be explored. Through bioinformatics analysis, we first found that NXPH4 was independently related to the prognosis of patients with bladder cancer. Through wound healing assays, transwell invasion assays, and plate clone formation assays, we found that NXPH4 promoted the proliferation, migration, and invasion of bladder cancer cells. The induced gemcitabine resistance cell line also showed a higher expression of NXPH4. A glycolytic activity assay demonstrated that the expression of NXPH4 was positively related to glycolysis. A higher level of reactive oxygen species caused by enhanced levels of NXPH4 was found in gemcitabine-resistant cell lines. NDUFA4L2, glycolysis, and reactive oxygen species were shown to be essential for NXPH4-regulated functions through rescue assays in cell lines. The roles of NXPH4-regulated glycolysis, gemcitabine resistance, and NDUFA4L2 were validated in vivo as well. Our results imply that NXPH4 contributes to the proliferation, migration, and invasion of bladder cancer by maintaining the stability of NDUFA4L2 and consequently activating reactive oxygen species and glycolysis. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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21 pages, 5206 KiB

Open AccessArticle

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer

by Lijiang Gu, Yuhang Chen, Xing Li, Yibo Mei, Jinlai Zhou, Jianbin Ma, Mengzhao Zhang, Tao Hou, Dalin He and Jin Zeng

Cancers 2022, 14(15), 3739; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153739 - 31 Jul 2022

Cited by 8 | Viewed by 2257

Abstract

RBPs in the development and progression of BC remains unclear. Here, we elucidated the role of RBPs in predicting the survival of patients with BC. Clinical information and RNA sequencing data of the training and validation cohorts were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Survival-related differentially expressed RBPs were identified using Cox regression analyses. A total of 113 upregulated and 54 downregulated RBPs were observed, with six showing prognostic values (AHNAK, MAP1B, LAMA2, P4HB, FASN, and GSDMB). In both the GSE32548 and GSE31684 datasets, patients with low-risk scores in survival-related six RBPs-based prognostic model showed longer overall survival than those with high-risk scores. AHNAK, MAP1B, P4HB, and FASN expression were significantly upregulated in both BC tissues and cell lines. BC tissues from high-risk group showed higher proportions of naive CD4+ T cells, M0 and M2 macrophages, and neutrophils and lower proportions of plasma cells, CD8+ T cells, and T-cell follicular helper compared to low-risk group. AHNAK knockdown significantly inhibited the proliferation, invasion, and migration of BC cells in vitro and inhibited the growth of subcutaneous tumors in vivo. We thus developed and functionally validated a novel six RBPs-based prognostic model for BC. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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12 pages, 1138 KiB

Open AccessArticle

Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics

by Khaled Bin Satter, Zach Ramsey, Paul M. H. Tran, Diane Hopkins, Gregory Bearden, Katherine P. Richardson, Martha K. Terris, Natasha M. Savage, Sravan K. Kavuri and Sharad Purohit

Cancers 2022, 14(13), 3242; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14133242 - 01 Jul 2022

Cited by 3 | Viewed by 1519

Abstract

Malignant chromophobe renal cancer (chRCC) and benign oncocytoma (RO) are two renal tumor types difficult to differentiate using histology and immunohistochemistry-based methods because of their similarity in appearance. We previously developed a transcriptomics-based classification pipeline with “Chromophobe-Oncocytoma Gene Signature” (COGS) on a single-molecule counting platform. Renal cancer patients (n = 32, chRCC = 17, RO = 15) were recruited from Augusta University Medical Center (AUMC). Formalin-fixed paraffin-embedded (FFPE) blocks from their excised tumors were collected. We created a custom single-molecule counting code set for COGS to assay RNA from FFPE blocks. Utilizing hematoxylin-eosin stain, pathologists were able to correctly classify these tumor types (91.8%). Our unsupervised learning with UMAP (Uniform manifold approximation and projection, accuracy = 0.97) and hierarchical clustering (accuracy = 1.0) identified two clusters congruent with their histology. We next developed and compared four supervised models (random forest, support vector machine, generalized linear model with L2 regularization, and supervised UMAP). Supervised UMAP has shown to classify all the cases correctly (sensitivity = 1, specificity = 1, accuracy = 1) followed by random forest models (sensitivity = 0.84, specificity = 1, accuracy = 1). This pipeline can be used as a clinical tool by pathologists to differentiate chRCC from RO. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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13 pages, 2339 KiB

Open AccessArticle

DJ-1 Expression Might Serve as a Biologic Marker in Patients with Bladder Cancer

by Shuhei Hirano, Kazumasa Matsumoto, Kei Tanaka, Noriyuki Amano, Dai Koguchi, Masaomi Ikeda, Yuriko Shimizu, Benio Tsuchiya, Ryo Nagashio, Yuichi Sato and Masatsugu Iwamura

Cancers 2022, 14(10), 2535; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14102535 - 21 May 2022

Cited by 3 | Viewed by 1810

Abstract

The overexpression of DJ-1 protein and its secretion into the bloodstream has been reported in various neoplasms. However, serum levels and the subcellular localization of DJ-1 have not been analyzed in detail in bladder cancer (BC). Our comprehensive analysis of these variables started with the measurement of DJ-1 in serum from 172 patients with BC, 20 patients with urolithiasis and 100 healthy participants. Next, an immunohistochemical study of DJ-1 expression and localization was conducted in 92 patients with BC, and associations with clinicopathologic factors and patient outcomes were evaluated. Serum DJ-1 was significantly higher in patients with BC than in those with urolithiasis or in healthy participants. Immunohistochemically, a cytoplasm-positive (Cy+) and nucleus-negative (N−) DJ-1 pattern was associated with age and pathologic stage. Log-rank tests indicated that the Cy+, N− pattern was significantly associated with overall survival (OS), recurrence-free survival (RFS), and cancer specific survival (CSS). In addition, the Cy+, N− pattern was an independent prognostic factor in the multivariate analysis adjusted for the effects of the clinicopathologic outcomes. The investigation of DJ-1 expression might help physicians to make decisions regarding further follow-up and additional treatments. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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19 pages, 2568 KiB

Open AccessArticle

Characterization of the Peri-Membrane Fluorescence Phenomenon Allowing the Detection of Urothelial Tumor Cells in Urine

by Charly Gutierrez, Xavier Pinson, Kathleen Jarnouen, Marine Charpentier, Raphael Pineau, Laëtitia Lallement and Rémy Pedeux

Cancers 2022, 14(9), 2171; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092171 - 26 Apr 2022

Cited by 1 | Viewed by 2039

Abstract

Urine cytology is non-invasive, easy to collect, with medium sensitivity and a high specificity. It is an effective way to detect high-grade bladder cancer (BC), but it is less effective on low-grade BC because the rate of equivocal results is much higher. Recently, the fluorescent properties of plasma membranes of urothelial tumor cells (UTC) found in urine cytology have been shown to be useful in improving the early detection of BC. This phenomenon is called peri-membrane fluorescence (PMF). Based on previous studies that have identified the PMF on UTCs, the main objective was to characterize this phenomenon. For this study, a software was specially created to quantify the PMF of all tested cells and different treatments performed. PMF was not found to be a morphological and discriminating feature of UTCs, all cells in shape and not from urine show PMF. We were able to highlight the crucial role of plasma membrane integrity in the maintenance of PMF. Finally, it was found that the induction of a strong cellular stress induced a decrease in PMF, mimicking what was observed in non-tumor cells collected from urine. These results suggest that PMF is found in cells able to resist this stress, such as tumor cells. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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12 pages, 2729 KiB

Open AccessArticle

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

by Takuto Shimizu, Makito Miyake, Nobutaka Nishimura, Kuniaki Inoue, Koyo Fujii, Yusuke Iemura, Kazuki Ichikawa, Chihiro Omori, Mitsuru Tomizawa, Fumisato Maesaka, Yuki Oda, Tatsuki Miyamoto, Keiichi Sakamoto, Keisuke Kiba, Masahiro Tanaka, Nobuo Oyama, Eijiro Okajima, Ken Fujimoto, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Kazumasa Torimoto, Nobumichi Tanaka and Kiyohide Fujimoto Show full author list Hide full author list

Cancers 2022, 14(7), 1735; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071735 - 29 Mar 2022

Cited by 7 | Viewed by 2129

Abstract

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30–40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63–22.4) p < 0.0001; HR 3.63 (1.97–6.69), p < 0.0001; HR 2.75 (1.35–5.59), p = 0.0053; and HR 3.17 (1.00–10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02–0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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19 pages, 9425 KiB

Open AccessArticle

Targeting circDGKD Intercepts TKI’s Effects on Up-Regulation of Estrogen Receptor β and Vasculogenic Mimicry in Renal Cell Carcinoma

by Jie Ding, Xin-Gang Cui, Hao-Jie Chen, Yin Sun, Wei-Wei Yu, Jie Luo, Guang-Qian Xiao, Chawnshang Chang, Jun Qi and Shuyuan Yeh

Cancers 2022, 14(7), 1639; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071639 - 23 Mar 2022

Cited by 4 | Viewed by 1954

Abstract

Vasculogenic mimicry (VM) has been reported as an alternative channel to increase tumor nutrient supplies and accelerate tumor progression, and is associated with poor survival prognosis in multiple cancers, including renal cell carcinoma (RCC). The currently used anti-angiogenic treatment for metastatic RCC, sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation. Previously we identified that the estrogen receptor β (ERβ) functions as an oncogenic factor to promote RCC progression, supported by the analytic results from The Cancer Genome Atlas (TCGA) database. We have also found evidence that sunitinib induces RCC VM formation by up-regulating ERβ expression. In this study, we further demonstrated that treatment with sunitinib, as well as axitinib, another TKI, could induce ERβ expression in RCC cell lines. Clinical clear cell RCC (ccRCC) patients with higher ERβ expression are more likely to be found VE-cadherin positive and VM positive. Mechanism dissection showed that TKI- induced ERβ transcriptionally up-regulates the circular RNA of DGKD (circDGKD, hsa_circ_0058763), which enhances VE-cadherin expression by sponging the microRNA miR-125-5p family. Targeting circDGKD intercepts sunitinib-pretreatment-induced RCC VM formation, reduces metastases and improves survival in an experimental orthotopic animal model. Targeting ERβ/circDGKD signals may improve the TKI efficacy and provide novel combination therapies for metastatic RCC. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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11 pages, 1391 KiB

Open AccessArticle

Expression of Membranous CD155 Is Associated with Aggressive Phenotypes and a Poor Prognosis in Patients with Bladder Cancer

by Kohei Mori, Kazumasa Matsumoto, Noriyuki Amano, Dai Koguchi, Soichiro Shimura, Masahiro Hagiwara, Yuriko Shimizu, Masaomi Ikeda, Yuichi Sato and Masatsugu Iwamura

Cancers 2022, 14(6), 1576; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061576 - 19 Mar 2022

Cited by 3 | Viewed by 2149

Abstract

Objective: To investigate the relationship between clinicopathological findings and membranous CD155 (mCD155) or cytoplasmic CD155 (cCD155) expression in bladder cancer (BC). Methods: We retrospectively analyzed 103 patients with BC who underwent radical cystectomy between 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining was performed to evaluate CD155 expression in tumor cells. Cases with > 10% expression on the membrane or cytoplasm of tumor cells were positive. The Fisher′s exact test was used for categorical variables and the Kaplan–Meier method was used for survival outcomes. Univariate and multivariate Cox regression hazard models were used to evaluate the survival risk factors. Results: Cases that were mCD155-positive were associated with high-grade tumors (p = 0.02), nodal status (p < 0.01), and pT stage (p = 0.04). No association with any clinicopathological factor was observed in the cCD155 cases. Kaplan–Meier analysis showed that mCD155-positive cases had shorter periods of recurrence-free survival (p = 0.015) and cancer-specific survival (p = 0.005). Only nodal status was an independent predictor for both cancer-specific survival and recurrence-free survival in multivariate analysis (p = 0.02 and p < 0.01, respectively). Conclusion: mCD155 expression may be a marker of an aggressive phenotype and a poor prognosis in patients with BC. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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14 pages, 4178 KiB

Open AccessArticle

CD103+ Tissue Resident T-Lymphocytes Accumulate in Lung Metastases and Are Correlated with Poor Prognosis in ccRCC

by Christine Sanders, Almotasem Salah M. Hamad, Susanna Ng, Racha Hosni, Jörg Ellinger, Niklas Klümper, Manuel Ritter, Carsten Stephan, Klaus Jung, Michael Hölzel, Glen Kristiansen, Stefan Hauser and Marieta I. Toma

Cancers 2022, 14(6), 1541; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061541 - 17 Mar 2022

Cited by 7 | Viewed by 2023

Abstract

Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor with variable responses to immune checkpoint therapy. The significance of the immune cell infiltrate in distant metastases, their association with the immune infiltrate in the primary tumors and their impact on prognosis are poorly described. We hypothesized that specific subtypes of immune cells may be involved in the control of metastases and may have an impact on the prognosis of ccRCC. We analyzed the immune microenvironment in ccRCC primary tumors with distant metastases, paired distant metastases and non-metastasized ccRCC (n = 25 each group) by immunohistochemistry. Confirmatory analyses for CD8+ and CD103+ cells were performed in a large ccRCC cohort (n = 241) using a TCGA-KIRC data set (ITGAE/CD103). High immune cell infiltration in primary ccRCC tumors was significantly correlated with the development of distant tumor metastasis (p < 0.05). A high density of CD103+ cells in ccRCC was more frequent in poorly differentiated tumors (p < 0.001). ccRCCs showed high levels of ITGAE/CD103 compared with adjacent non-neoplastic tissue. A higher density of CD103+ cells and a higher ITGAE/CD103 expression were significantly correlated with poor overall survival in ccRCC (log rank p < 0.05). Our results show a major prognostic value of the immune pattern, in particular CD103+ cell infiltration in ccRCC, and highlight the importance of the tumor immune microenvironment. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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16 pages, 4490 KiB

Open AccessArticle

Identification of Survival and Therapeutic Response-Related Ferroptosis Regulators in Bladder Cancer through Data Mining and Experimental Validation

by Pu Zhang, Zijian Liu, Decai Wang, Yunxue Li, Yuan Zhang and Yajun Xiao

Cancers 2021, 13(23), 6069; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13236069 - 02 Dec 2021

Cited by 4 | Viewed by 2285

Abstract

Ferroptosis has been reported to regulate tumorigenesis, metastasis, drug resistance and the immune response. However, the potential roles of ferroptosis regulators in the advancement of bladder cancer remain to be explored. We systematically evaluated the multidimensional alteration landscape of ferroptosis regulators in bladder cancer and checked if their expression correlated with the ferroptosis index. We used least absolute shrinkage and selection operator regression to form a signature consisting of seven ferroptosis regulator. We confirmed the signature’s prognostic and predictive accuracy with five independent datasets. A nomogram was built to predict the overall survival and risk of death of patients. The relative expression of the genes involved in the signature was also clarified by real-time quantitative PCR. We found the risk score was related to tumor progression and antitumor immunity-related pathways. Moreover, there existed negative association between the relative antitumor immune cell infiltration level and the risk score, and higher tumor mutation burden was found in the group of lower risk score. We used The Tumor Immune Dysfunction and Exclusion database and IMvigor210 cohort having immunotherapy efficacy results to confirm the prediction function of the risk score. Furthermore, the ferroptosis regulator signature could also reflect the chemotherapy sensitivity of bladder cancer. Full article

(This article belongs to the Special Issue Insights into Urologic Cancer)

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