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Abstract Background With over 65,000 new cases per year in Germany, prostate cancer (PC) is the most common cancer in men in Germany. Localized PC is often treated by radical prostatectomy and has a very good prognosis. Postoperative quality of life (QoL) is significantly influenced by the side effects of surgery. One possible approach to improve QoL is postoperative symptom monitoring using ePROMs (electronic patient-reported outcome measures) to accurately identify any need for support. Methods The PRO-P (“Influence of ePROMS in surgical therapy of PC on the postoperative course”) study is a randomized controlled trial employing 1:1 randomization at 6 weeks postoperatively, involving 260 patients with incontinence (≥ 1 pad/day) at six participating centers. Recruitment is planned for 1 year with subsequent 1-year follow-up. PRO-monitoring using domains of EPIC-26, psychological burden, and QoL are assessed 6, 12, 18, 24, 36, and 52 weeks postoperatively. Exceeding predefined PRO-score cutoffs triggers an alert at the center, prompting patient contact, medical consultation, and potential interventions. The primary endpoint is urinary continence. Secondary endpoints refer to EPIC-26 domains, psychological distress, and QoL. Aspects of feasibility, effect, and implementation of the intervention will be investigated within the framework of a qualitative process evaluation. Discussion PRO-P investigates the effect on postoperative symptom monitoring of a structured follow-up using ePROMs in the first year after prostatectomy. It is one of the first studies in cancer surgery investigating PRO-monitoring and its putative applicability to routine care. Patient experiences with intensified monitoring of postoperative symptoms and reflective counseling will be examined in order to improve primarily urinary continence, and secondly other burdens of physical and psychological symptoms, quality-of-life, and patient competence. The potential applicability of the intervention in clinical practice is facilitated by IT adaption to the certification standards of the German Cancer Society and the integration of the ePROMs survey via a joint patient portal. Positive outcomes could readily translate this complex intervention into routine clinical care. PRO-P might improve urinary incontinence and QoL in patients with radical prostatectomy through the structured use of ePROMs. Trial registration ClinicalTrials.gov NCT05644821. Registered on 09 December 2022.

Abstract Background Few diagnostic and prognostic biomarkers are available for head-and-neck squamous cell carcinoma (HNSCC). Long non-coding RNAs (lncRNAs) have shown promise as biomarkers in other cancer types and in some cases functionally contribute to tumor development and progression. Here, we searched for lncRNAs useful as biomarkers in HNSCC. Methods Public datasets were mined for lncRNA candidates. Two independent HNSCC tissue sets and a bladder cancer tissue set were analyzed by RT-qPCR. Effects of lncRNA overexpression or downregulation on cell proliferation, clonogenicity, migration and chemosensitivity were studied in HNSCC cell lines. Results Data mining revealed prominently CASC9, a lncRNA significantly overexpressed in HNSCC tumor tissues according to the TCGA RNAseq data. Overexpression was confirmed by RT-qPCR analyses of patient tissues from two independent cohorts. CASC9 expression discriminated tumors from normal tissues with even higher specificity than HOTAIR, a lncRNA previously suggested as an HNSCC biomarker. Specificity of HNSCC detection by CASC9 was further improved by combination with HOTAIR. Analysis of TCGA pan-cancer data revealed significant overexpression of CASC9 across different other entities including bladder, liver, lung and stomach cancers and especially in squamous cell carcinoma (SCC) of the lung. By RT-qPCR analysis we furthermore detected stronger CASC9 overexpression in pure SCC of the urinary bladder and mixed urothelial carcinoma with squamous differentiation than in pure urothelial carcinomas. Thus, CASC9 might represent a general diagnostic biomarker and particularly for SCCs. Unexpectedly, up- or downregulation of CASC9 expression in HNSCC cell lines with low or high CASC9 expression, respectively, did not result in significant changes of cell viability, clonogenicity, migration or chemosensitivity. Conclusions CASC9 is a promising biomarker for HNSCC detection. While regularly overexpressed, however, this lncRNA does not seem to act as a major driver of development or progression in this tumor.

The INK4/ARF locus at chromosome 9p21 encoding p14ARF, p15INK4B and p16INK4A is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC). In addition to deletions and DNA hypermethylation, further epigenetic mechanisms might underlie its repression. One candidate factor is the long noncoding RNA ANRIL, which recruits Polycomb proteins (PcG) to regulate expression of target genes in cis and trans. We observed ANRIL overexpression in many UC tissues and cell lines mainly resulting from upregulation of 3’-truncated isoforms. However, aberrant ANRIL expression was neither associated with repression of INK4/ARF genes nor with proliferation activity or senescence. We wondered whether truncated ANRIL isoforms exhibit altered properties resulting in loss of function in cis. We excluded delocalization and performed RNA immunoprecipitation demonstrating interaction between full length or truncated ANRIL and PcG protein CBX7, but not SUZ12 of PRC2. Our data indicate that ANRIL in UC cells may not interact with PRC2, which is central for initializing gene repression. Thus, tissue-specific binding activities between ANRIL and PcG proteins may determine the regulatory function of ANRIL. In conclusion, ANRIL does not play a major role in repression of the INK4/ARF locus in UC.

Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to stratify patients by molecular subtype, thus aiding personalized treatments.