Accuracy, safety, and diagnostic prediction of percutaneous renal mass biopsy and subsequent changes in treatment.

Introduction: The incidence of renal tumours is increasing annually, and imaging alone cannot meet the diagnostic needs. Aim: This single-centre study aimed to evaluate the predictors of diagnostic imaging-guided percutaneous renal mass biopsy (PRMB), its accuracy and safety, and subsequent changes to the treatment plan. Material and methods: We retrospectively collected the clinical data of patients who had undergone PRMB. The diagnosis rate, pathological data, and complications were analysed. Potential predictors of a diagnostic PRMB were evaluated using logistic regression analysis. Changes to the treatment plan due to PRMB results were also analysed. Results: A total of 158 patients were included in this study. The univariate analysis showed that higher tumour diameter (OR = 1.223, 95% CI: 1.018-1.468, p = 0.031) and number of biopsy cores ≥ 2 (OR = 6.125, 95% CI: 2.006-18.703, p = 0.001) were significantly associated with diagnostic biopsy, and multivariate analysis results showed that higher tumour diameter (OR = 1.215, 95% CI: 1.008-1.463, p = 0.041) was an independent predictor of diagnostic biopsy. A nomogram including tumour diameter and number of biopsy cores was constructed to predict diagnostic biopsy. Compared with postoperative pathology, the concordance between biopsy and postoperative pathology at identifying malignancies, histologic type, and histologic grade were 100% (47/47), 85.1% (40/47), and 54.1% (20/37), respectively. The treatment plans of 15 patients (9.5%) changed based on the PRMB results. Fourteen patients (8.9%) had minor complications (Clavien-Dindo classification < 2). Conclusions: Our results suggest that tumour diameter was an independent predictor of diagnostic biopsy. Furthermore, PRMB can be accurately and safely performed and may guide clinical decision-making for patients with renal tumours.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a frequent urological malignancy characterized by a high rate of metastasis and lethality. The treatment strategy for advanced RCC has moved through multiple iterations over the past three decades. Initially, cytokine treatment was the only systemic treatment option for patients with RCC. With the development of medicine, antiangiogenic agents targeting vascular endothelial growth factor and mammalian target of rapamycin and immunotherapy, immune checkpoint inhibitors (ICIs) have emerged and received several achievements in the therapeutics of advanced RCC. However, ICIs have still not brought completely satisfactory results due to drug resistance and undesirable side effects. For the past years, the interests form researchers have been attracted by the combination of ICIs and targeted therapy for advanced RCC and the angiogenesis and immunogenic tumor microenvironmental variations in RCC. Therefore, we emphasize the potential principle and the clinical progress of ICIs combined with targeted treatment of advanced RCC, and summarize the future direction.

P300/SP1 complex mediating elevated METTL1 regulates CDK14 mRNA stability via internal m7G modification in CRPC.

BACKGROUND: N7-methylguanosine (m7G) modification is, a more common epigenetic modification in addition to m6A modification, mainly found in mRNA capsids, mRNA interiors, transfer RNA (tRNA), pri-miRNA, and ribosomal RNA (rRNA). It has been found that m7G modifications play an important role in mRNA transcription, tRNA stability, rRNA processing maturation, and miRNA biosynthesis. However, the role of m7G modifications within mRNA and its "writer" methyltransferase 1(METTL1) in tumors, particularly prostate cancer (PCa), has not been revealed. METHODS: The differential expression level of METTL1 between hormone-sensitive prostate cancer (HSPC) and castrate-resistant prostate cancer (CRPC) was evaluated via RNA-seq and in vitro experiments. The effects of METTL1 on CRPC progression were investigated through in vitro and in vivo assays. The upstream molecular mechanism of METTL1 expression upregulation and the downstream mechanism of its action were explored via Chromatin Immunoprecipitation quantitative reverse transcription polymerase chain reaction (CHIP-qPCR), Co-immunoprecipitation (Co-IP), luciferase reporter assay, transcriptome-sequencing, m7G AlkAniline-Seq, and mRNA degradation experiments, etc. RESULTS AND CONCLUSION: Here, we found that METTL1 was elevated in CRPC and that patients with METTL1 elevation tended to have a poor prognosis. Functionally, the knockdown of METTL1 in CRPC cells significantly limited cell proliferation and invasive capacity. Mechanistically, we unveiled that P300 can form a complex with SP1 and bind to the promoter region of the METTL1 gene via SP1, thereby mediating METTL1 transcriptional upregulation in CRPC. Subsequently, our findings indicated that METTL1 leads to enhanced mRNA stability of CDK14 by adding m7G modifications inside its mRNA, ultimately promoting CRPC progression.

TEAD3 inhibits the proliferation and metastasis of prostate cancer via suppressing ADRBK2.

TEAD3 acts as a transcription factor in many tumors to promote tumor occurrence and development. But in prostate cancer (PCa), it appears as a tumor suppressor gene. Recent studies have shown that this may be related to subcellular localization and posttranslational modification. We found that TEAD3 was down-expressed in PCa. Immunohistochemistry of clinical PCa specimens confirmed that TEAD3 expression was the highest in benign prostatic hyperplasia (BPH) tissues, followed by primary PCa tissues, and the lowest in metastatic PCa tissues, and its expression level was positively correlated with overall survival. MTT assay, clone formation assay, and scratch assay confirmed that overexpression of TEAD3 could significantly inhibit the proliferation and migration of PCa cells. Next-generation sequencing results indicated that Hedgehog (Hh) signaling pathway was significantly inhibited after overexpression of TEAD3. Rescue assays suggested that ADRBK2 could reverse the proliferation and migration ability caused by overexpression of TEAD3. TEAD3 is downregulated in PCa and associated with poor patient prognosis. Overexpression of TEAD3 inhibits the proliferation and migration ability of PCa cells via restraining the mRNA level of ADRBK2. These results indicate that TEAD3 was down-expressed in PCa patients and was positively correlated with a high Gleason score and poor prognosis. Mechanistically, we found that the upregulation of TEAD3 inhibits the proliferation and metastasis of prostate cancer by inhibiting the expression of ADRBK2.