Ye, Dingwei

Increasing evidence demonstrated that noncoding RNA is abnormally expressed in cancer tissues and serves a vital role in tumorigenesis, tumor development, and metastasis. The aim of the present study was to determine an lncRNA signature in order to predict the overall survival (OS) of patients with muscle-invasive bladder cancer (MIBC). A total of 246 patients with pathologically confirmed MIBC in The Cancer Genome Atlas (TCGA) dataset were recruited and included in the present study. We choose patients who have smoked less (including never smoking) or more than 15 years. A total of 44 differentially expressed lncRNAs were identified with a fold change larger than 1.5 and a P value < 0.05 through the limma package. Subsequently, a comparison between patients with no tobacco smoke exposure for <15 years and patients who had been exposed to tobacco smoke for >15 years was performed by using the matchIt package. Among the 44 differentially expressed lncRNAs, 5 lncRNAs were identified to be significantly associated with OS. Based on the characteristic risk scores of these 5 lncRNAs, patients were divided into low-risk and high-risk groups and exhibited significant differences in OS. Multivariate Cox regression analysis demonstrated that the 5-lncRNA signature was independent of age, tumor-node metastasis (TNM) staging, lymphatic node status, and adjuvant postoperative radiotherapy. In the present study, a novel 5-lncRNA signature was developed and was demonstrated to be useful in predicting the survival of patients with MIBC. If validated, this lncRNA signature may assist in the selection of a high-risk subpopulation that requires more aggressive therapeutic intervention. The risk scores involved in several associated pathways were identified using gene set enrichment analysis (GSEA). However, the clinical implications and mechanism of these 5 lncRNAs require further investigation.

AbstractMolecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node‐positive penile SCC. Patients with node‐positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer‐specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3‐CpG‐based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P < .001). The addition of the methylation score significantly improved the pN‐stage C‐index from 0.70 to 0.79 (incremental C = 0.09, P < .001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN‐stage C‐index from 0.69 to 0.78 (incremental C = 0.09, P < .001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node‐positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high‐risk group may benefit from more aggressive therapy or clinical trials.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and Methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk‐calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m‐R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN 3 , and ILNM ratio were associated with higher recurrence rate. The 2‐year OS rates were lower for patients with high (>37%) and intermediate (19–37%) compared to low (<19%) 24m‐R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment ( P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts ( P > 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.