Nesprin1 deficiency is associated with poor prognosis of renal cell carcinoma and resistance to sunitinib treatment.

INTRODUCTION: Nuclear envelope spectrin repeat protein (Nesprin) 1 encoded by SYNE1, crucially regulates the morphology and functions of the cell. Mutations in the SYNE1 gene are associated with various diseases; however, their significance in renal cell carcinoma (RCC) remains unknown. In this study, we have investigated the association of SYNE1/Nesprin1 with the progression and prognosis of clear cell RCC (ccRCC). METHODS: In silico analyses of publicly available datasets of patients with RCC were performed. Based on the cohort data, Nesprin1 expression in nephrectomized tissue samples acquired from patients with ccRCC was analyzed using immunohistochemical staining. The invasion, migration, and proliferation of the SYNE1-knockdown human RCC cell lines were analyzed in vitro; moreover, RNA sequencing and Gene Set Enrichment Analysis were conducted to study the molecular mechanism underlying the association of SYNE1/Nesprin1 with prognosis of RCC. RESULTS: Patients with RCC-associated SYNE1 gene mutations exhibited significantly worse overall and progression-free survivals. Patients with Nesprin1-negative ccRCC tumors exhibit significantly poorer overall, cancer-specific, and recurrence-free survival rates than those recorded in the Nesprin1-positive group. SYNE1 knockdown enhanced the invasion and migration of RCC cells, however, it did not influence the proliferation of cells. RNA sequencing and Gene Set Enrichment Analysis revealed that SYNE1 knockdown significantly altered the expression of genes associated with oxidative phosphorylation. Consistently, patients with RCC exhibiting low SYNE1 expression, who were treated with the vascular endothelial growth factor receptor inhibitor sunitinib, had worse progression-free survival. CONCLUSIONS: The results indicate that the expression of SYNE1/Nesprin1 and SYNE1 mutations in patients with RCC are closely linked to their prognosis and responsiveness to sunitinib treatment.

Comprehensive genomic profiling testing in Japanese castration-resistant prostate cancer patients: results of a single-center retrospective cohort study.

OBJECTIVE: Comprehensive genomic profiling testing using a hybrid-capture next-generation sequencing is commonly used in clinical practice to employ precision medicine in cancer treatment worldwide. In this study, we aimed to analyze the profiles obtained using comprehensive genomic profiling testing that was performed in Japanese castration-resistant prostate cancer patients and to discuss the genetic findings in a real-world setting. METHODS: A total of 60 cases and 57 castration-resistant prostate cancer patients underwent comprehensive genomic profiling testing between 1 January 2021 and 31 December 2022. Four types of comprehensive genomic profiling testing were selected, and clinically significant cancer-specific gene alterations were identified. RESULTS: The median age of patients was 74 years, and the median prostate-specific antigen value at the time of submission was 18.6 ng/ml. Fifty-seven (95%) of 60 cases were metastatic castration-resistant prostate cancers, and 3 cases (5%) were non-metastatic. Among all genetic alterations, androgen-receptor alteration was the most frequently detected in 17 cases (28.3%), followed by 15 cases of TP53 (25.0%), 14 cases of CDK12 (23.3%), 10 cases of phosphatase and tensin homolog (16.7%) and 9 cases of ATM (15.0%) mutations. A total of 13 patients (21.7%) received systemic therapy according to the comprehensive genomic profiling testing results. Overall, the survival rate was significantly greater in the group treated through systemic therapy based on comprehensive genomic profiling testing compared with the group without new therapeutic treatment (P = 0.041). CONCLUSIONS: Comprehensive genomic profiling testing is recommended in castration-resistant prostate cancer patients identified as resistant to standard therapy as this can provide a new therapeutic option.

Histopathological Analysis of False-positive Lesions in mpMRI/TRUS Fusion Prostate Biopsy.

BACKGROUND/AIM: Multi-parametric magnetic resonance imaging (mpMRI)/ultrasonography fusion prostate biopsy (FB) is a more accurate method of diagnosis than conventional prostate biopsy, but false-positive lesions still exist. Limited studies have examined the cause of false-positive lesions by histological analysis. PATIENTS AND METHODS: We examined 322 patients who underwent mpMRI/transrectal ultrasonography (TRUS) FB. We classified prostate imaging-recording and data system (PI-RADS) 3 and PI-RADS 4-5 as low PI-RADS lesions and high PI-RADS lesions, respectively. In total, 105 lesions were identified as false-positive lesions. We performed histological analysis of atrophy, hyperplasia, and lymphocyte infiltration in these lesions, comparing low PI-RADS lesions and high PI-RADS lesions. RESULTS: The frequencies of prostate hyperplasia and lymphocyte infiltration were higher in high PI-RADS lesions than in low PI-RADS lesions (p=0.028 and 0.024, respectively). There was no significant difference regarding atrophy (p=0.295). CONCLUSION: Histopathological change may be one of the reasons for false-positive lesions.

Primary adenocarcinoma of the rete testis with elevated serum CA19-9 antigen levels.

Primary adenocarcinoma of the rete testis is an extremely rare tumor with a poor prognosis. Herein, we report a case of primary adenocarcinoma of the rete testis accompanied by elevated serum carbohydrate antigen 19-9 (CA19-9) antigen levels in a 44-year-old man who presented with left scrotal swelling. Para-aortic lymph node swelling was observed on the computed tomography scan. Germ cell tumor markers were within the normal range, but serum CA19-9 antigen levels were high. Radical orchiectomy was performed, and histological examination revealed primary adenocarcinoma of the rete testis with no evidence of other primary carcinomas. The patient underwent three lines of chemotherapy, although no reports suggest the use of gemcitabine and oxaliplatin (GEMOX) in a patient with adenocarcinoma of the rete testis. Unfortunately, he developed metastasis at multiple sites and passed away due to adenocarcinoma 13 months after undergoing orchiectomy. Some reports suggest that CA19-9 antigen levels are elevated in patients with adenocarcinoma of the rete testis, although it has not been clarified whether elevated CA19-9 antigen levels reflect the progression of adenocarcinoma of the rete testis. In this case, as CA19-9 antigen levels increased with progression, CA19-9 might be a marker for primary adenocarcinoma of the rete testis. GEMOX chemotherapy as a line of treatment in primary adenocarcinoma of the rete testis has not been reported. Therefore, further studies must evaluate the efficacy of the aforementioned chemotherapy regimen.

Renal metastasis from primary hepatocellular carcinoma: a case report.

We report a rare case of renal metastasis from primary hepatocellular carcinoma (HCC). A mass in the right kidney of a 71-year-old man was detected by follow-up computed tomography (CT) for HCC. He was diagnosed as having primary HCC 18 years ago and had undergone partial hepatectomy, transarterial chemoembolization, and pulmonary segmentectomy for primary HCC and its metastasis over 10 years. Eight years after this, follow-up CT revealed a right kidney mass, and laboratory testing showed an elevated level of protein induced by vitamin K absence II (PIVKA-II). We performed laparoscopic radical nephrectomy for the right kidney mass. Histopathology revealed renal metastasis from primary HCC. To date, only a small number of cases of renal metastasis from HCC have been reported.

Fibroblast Growth Factor Family in the Progression of Prostate Cancer.

Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play an important role in the maintenance of tissue homeostasis and the development and differentiation of prostate tissue through epithelial-stromal interactions. Aberrations of this signaling are linked to the development and progression of prostate cancer (PCa). The FGF family includes two subfamilies, paracrine FGFs and endocrine FGFs. Paracrine FGFs directly bind the extracellular domain of FGFRs and act as a growth factor through the activation of tyrosine kinase signaling. Endocrine FGFs have a low affinity of heparin/heparan sulfate and are easy to circulate in serum. Their biological function is exerted as both a growth factor binding FGFRs with co-receptors and as an endocrine molecule. Many studies have demonstrated the significance of these FGFs and FGFRs in the development and progression of PCa. Herein, we discuss the current knowledge regarding the role of FGFs and FGFRs-including paracrine FGFs, endocrine FGFs, and FGFRs-in the development and progression of PCa, focusing on the representative molecules in each subfamily.