Comprehensive Analysis of N6-Methylandenosine-Related lncRNAs in Clear Cell Renal Cell Carcinoma: A Correlation With Prognosis, Tumor Progression, and Therapeutic Response.

This study aims to develop a prognostic signature based on m6A-related lncRNAs for clear cell renal cell carcinoma (ccRCC). Differential expression analysis and Pearson correlation analysis were used to identify m6A-related lncRNAs associated with patient outcomes in The Cancer Genome Atlas (TCGA) database. Our approach led to the development of an m6A-related lncRNA risk score (MRLrisk), formulated using six identified lncRNAs: NFE4, AL008729.2, AL139123.1, LINC02154, AC124854.1 and ARHGAP31-AS1. Higher MRLrisk was identified as a risk factor for patients' prognosis in ccRCC. Furthermore, an MRLrisk-based nomogram was developed and demonstrated as a reliable tool for prognosis prediction in ccRCC. Enrichment analysis and tumor mutation signature studies were conducted to investigate MRLrisk-related biological phenotypes. The tumor immune dysfunction and exclusion (TIDE) score was employed to infer patients' response to immunotherapy, indicating a negative correlation between high MRLrisk and immunotherapy response. Our focus then shifted to LINC02154 for deeper exploration. We assessed LINC02154 expression in 28 ccRCC/normal tissue pairs and 3 ccRCC cell lines through quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, including EdU incorporation, flow cytometry and transwell assays, were performed to assess the role of LINC02154 in ccRCC cell functions, discovering that its downregulation hinders cancer cell proliferation and migration. Furthermore, the influence of LINC02154 on ccRCC cells' sensitivity to Sunitinib was explored using CCK-8 assays, demonstrating that decreased LINC02154 expression increases Sunitinib sensitivity. In summary, this study successfully developed an MRLrisk model with significant prognostic value for ccRCC and established LINC02154 as a critical biomarker and prospective therapeutic target in ccRCC management.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Correction: Atomically flat semiconductor nanoplatelets for light-emitting applications.

Correction for 'Atomically flat semiconductor nanoplatelets for light-emitting applications' by Bing Bai et al., Chem. Soc. Rev., 2023, 52, 318-360, https://doi.org/10.1039/D2CS00130F.

Atomically flat semiconductor nanoplatelets for light-emitting applications.

The last decade has witnessed extensive breakthroughs and significant progress in atomically flat two-dimensional (2D) semiconductor nanoplatelets (NPLs) in terms of synthesis, growth mechanisms, optical and electronic properties and practical applications. Such NPLs have electronic structures similar to those of quantum wells in which excitons are predominantly confined along the vertical direction, while electrons are free to move in the lateral directions, resulting in unique optical properties, such as extremely narrow emission line width, short photoluminescence (PL) lifetime, high gain coefficient, and giant oscillator strength transition (GOST). These unique optical properties make NPLs favorable for high color purity light-emitting applications, in particular in light-emitting diodes (LEDs), backlights for liquid crystal displays (LCDs) and lasers. This review article first introduces the intrinsic characteristics of 2D semiconductor NPLs with atomic flatness. Subsequently, the approaches and mechanisms for the controlled synthesis of atomically flat NPLs are summarized followed by an insight on recent progress in the mediation of core/shell, core/crown and core/crown@shell structures by selective epitaxial growth of passivation layers on different planes of NPLs. Moreover, an overview of the unique optical properties and the associated light-emitting applications is elaborated. Despite great progress in this research field, there are some issues relating to heavy metal elements such as Cd2+ in NPLs, and the ambiguous gain mechanisms of NPLs and others are the main obstacles that prevent NPLs from widespread applications. Therefore, a perspective is included at the end of this review article, in which the current challenges in this stimulating research field are discussed and possible solutions to tackle these challenges are proposed.

Pancreatic cancer detected with 18F-FDG PET/CT in a case of IgG4-related disease.

We present a case of a 67-year-old male presenting with severe abdominal pain, laboratory tests revealed IgG levels of 63.5 g/L, IgG4 levels of 63.7 g/L, and negative results for ANCA (Anti-Neutrophil Cytoplasmic Antibodies), Hematuria immunofixation electrophoresis, as well as Cold globulin qualitative test. 18F-FDG PET/CT revealed multiple lesions with increased metabolism in the submaxillary saliva gland, intrahepatic bile ducts, prostate, seminal vesicle glands, and the body of the pancreas. Additionally, a circular cystic-solid lesion with metabolic heterogeneity was observed in the head of the pancreas, accompanied by visible dilatation of the pancreatic duct. The diagnostic imaging suggested IgG4-related disease (IgG4-RD), while pancreatic malignancy could not be definitively ruled out. The patient underwent fine-needle aspiration (FNA) biopsies of lung nodules and the prostate gland, all of which were consistent with the diagnosis of IgG4-RD. Additionally, FNA biopsy of a pancreatic lesion is consistent with the diagnosis of pancreatic ductal adenocarcinoma.

[Applying Biomod2 for modeling of species suitable habitats:a case study of Paeonia lactiflora in China].

Paeonia lactiflora is an important medicinal resource in China. It is of great significance for the protection and cultivation of P. lactiflora resources to find the suitable habitats. The study was based on the information of 98 distribution sites and the data of 20 current environmental factors of wild P. lactiflora in China. According to the correlation and importance of environmental factors, we selected the main environmental factors affecting the potential suitable habitats. Then, BCC-CSM2-MR model was employed to predict the distribution range and center change of potential suitable habitat of wild P. lactiflora in the climate scenarios of SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5 during 2021-2100. The ensemble model combined with GBM, GLM, MaxEnt, and RF showed improved prediction accuracy, with TSS=0.85 and AUC=0.95. Among the 20 environmental factors, annual mean temperature, monthly mean diurnal range of temperature, temperature seasonality, mean temperature of the warmest quarter, precipitation of the wettest month, precipitation seasonality, precipitation of the driest quarter, and elevation were the main factors that affected the suitable habitat distribution of P. lactiflora. At present, the potential suitable habitats of wild P. lactiflora is mainly distributed in Inner Mongolia, Heilongjiang, Jilin, Liaoning, Hebei, Beijing, Shaanxi, Shanxi, Shandong, Gansu, Xinjiang, Tibet, and Ningxia, and concentrated in the northeastern Inner Mongolia, central Heilongjiang, and northern Jilin. Under future climate conditions, the highly sui-table area of wild P. lactiflora will shrink, and the potential suitable habitat will mainly be lost to different degrees. However, in the SSP5-8.5 scenario, the low suitable area of wild P. lactiflora will partially increase in the highlands and mountains in western China including Xinjiang, Tibet, and Qinghai during 2061-2100. The distribution center of wild P. lactiflora migrated first to the northeast and then to the southwest. The total suitable habitats were stable and kept in the high-latitude zones. The prediction of the potential geo-graphical distribution of P. lactiflora is of great significance to the habitat protection and standardized cultivation of this plant in the future.

Histopathological validation of safe margin for nephron-sparing surgery based on individual tumor growth pattern.

BACKGROUND: To evaluate the clinicopathologic value of morphological growth patterns of small renal cell carcinoma (sRCC) and determine the actual demand for taking a rim of healthy parenchyma to avoid positive SM. METHODS: Data was collected from 560 sRCC patients who underwent laparoscopic surgeries from May 2010 to October 2017. One hundred forty-nine cases received nephron-sparing surgery (NSS) and others received radical nephrectomy (RN). All specimens were analyzed separately by two uropathologists, and three morphological growth patterns were identified. The presence of pseudocapsule (PC), surgical margins (SM), and other routine variables were recorded. The relationship between growth patterns and included variables was measured by the χ2 test and Fisher's exact probability test. Survival outcomes were evaluated by Kaplan-Meier method and the log-rank test. RESULTS: The median age of patients was 63.2 years old and the mean tumor diameter was 3.0 cm. Four hundred eighty (85.7%) cases were clear cell RCC and 541 (96.6%) cases were at the pT1a stage. Peritumoral PC was detected in 512 (92.5%) specimens, and the ratio of tumor invasion in PC in infiltration pattern increased obviously than that of the other growth patterns. Similarly, the pT stage was significantly correlated with the infiltration pattern as well. One hundred forty-nine patients underwent NSS and 3 (2.0%) of them showed positive SM after operation. Statistical differences of the 5-year overall survival (OS) and the cancer-specific survival (CSS) existed between different morphological growth patterns, PC status, and pT stages. CONCLUSIONS: Morphological growth patterns of sRCC might be used as a potential biomarker to help operate NSS to avoid the risk of positive SM. How to distinguish different morphological growth patterns before operation and the effectiveness of the growth pattern as a novel proposed parameter to direct NSS in sRCC patients deserves further exploration.

Postoperative prognostic model for patients with clear cell renal cell carcinoma in a Chinese population.

OBJECTIVES: To develop a predictive model for the oncological outcomes of clear cell renal cell carcinoma in a Chinese population. METHODS: A retrospective study of 1108 patients with clear cell renal cell carcinoma who underwent nephrectomy or partial nephrectomy between January 2006 and December 2013 was carried out. Recurrence-free survival was calculated using Kaplan-Meier analysis. Differences between the groups were compared using the log-rank test. Cox proportional hazard regression was used to test associations between features and outcomes. The discriminative ability of the models was validated using Harrell's concordance index and bootstrapping. RESULTS: Overall, 942 patients who met the inclusion criteria had been followed. The median follow-up period was 72 months (range 1-143 months). Multivariate analysis showed that age, Eastern Cooperative Oncology Group performance status, preoperative platelet count, neutrophil-to-lymphocyte ratio, tumor size, 2010 tumor stage (pT3 and pT4) and Fuhrman nuclear grade were independent risk factors affecting recurrence-free survival in clear cell renal cell carcinoma patients (P < 0.05). These factors were assigned to develop a new model. The patients were divided into three groups based on the risk of recurrence. The difference among the prognoses of patients in the three groups was statistically significant (P < 0.05). The concordance index for our new model and that for Leibovich's 2018 model were 0.791 and 0.750, respectively. CONCLUSIONS: In the present study, the new model has a higher concordance index than does Leibovich's 2018 model of clear cell renal cell carcinoma in the Asian population, with no added pain for patients. This new model might be an appropriate risk stratification tool for clinical work.

Down-regulation of Sphk2 suppresses bladder cancer progression.

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. The abnormal expression of sphingosine kinase 2 (SphK2) is associated with tumor progression and a poor patient survival rate, however, the effect of SphK2 on the bladder cancer cells remains unclear. The aim of the paper was to study the expression of SphK2 in bladder cancer and the role of SphK2 on the cell proliferation, metastasis, and apoptosis in bladder cancer in vitro. Our results showed that SphK2 is up-regulated in bladder cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of SphK2 was significantly higher in human bladder cancer cells in comparison with normal bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a significant increase in the number of apoptotic cells. Furthermore, the transwell assay also showed significant cell migration inhibition in SphK2 siRNA transfectant compared with cell lines transfected with NC. Thus, this study suggested that SphK2 inhibition may provide a promising treatment for bladder cancer patients.

Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer.

BACKGROUND Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. MATERIAL AND METHODS We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. RESULTS We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. CONCLUSIONS Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese.

Radixin enhances colon cancer cell invasion by increasing MMP-7 production via Rac1-ERK pathway.

As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in many tumor tissues. However, little is known about its role in the progression of colon cancer. So we here aimed to determine the function of radixin in colon cancer cell invasion. Interestingly, we found that the expression of radixin was significantly elevated in colon cancer cells. Knockdown of radixin suppressed the invasion and migration of colon cancer cells. Further, knockdown of radixin inhibited the activation of Rac1 and ERK1/2, and decreased the expression and secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the radixin-promoted invasion and MMP-7 production. Together, our findings suggest that radixin enhances the invasion and migration of colon cancer cells. Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production may contribute to the function of radixin in the regulation of colon cancer cell invasion. Thus, radixin may act as a novel target for the diagnosis and treatment of colon cancer.

An ethnobotanical survey on the medicinal and edible plants used by the Daur people in China.

BACKGROUND: The Daur people are one of the 55 minority ethnic groups in China and have lived in Northern China for 300 years. In traditional Daur medicine, medicinal and edible plants (MEPs) are utilised for health benefits and therapeutic purposes; however, related ethnobotanical knowledge is rarely reported, which is disadvantageous for the sustainable development of these MEPs. METHODS: Semi-structured interviews with 122 informants, six focus group discussions, and a resource survey were conducted in a Daur minority nationality area in Inner Mongolia from 2015 to 2020, and the data statistics were analysed. In this study, we simulated a system dynamics model aimed at understanding the multiple feedback mechanisms involved in the relationships between the cultural influences and socioeconomic factors, sustainable environment, and development of MEPs. RESULTS: A total of 52 species of MEPs were identified and relevant ethnobotanical knowledge was assessed using Daur medicinal species data from Inner Mongolia and the Xinjiang region, with the literature and Ewenki ethnic group data used for comparison. The most commonly used medicinal plant species by the Daur were found to be Betula pendula subsp. mandshurica, Artemisia integrifolia, Crataegus pinnatifida, Saposhnikovia divaricata, Artemisia argyi, and Jacobaea cannabifolia. The MEPs most frequently targeted the digestive and rheumatic immunity systems, as well as infectious diseases or parasitic infections and other common diseases and basic health issues. MEP knowledge was primarily limited to older generations; thus, the valuable ethnobotanical knowledge on traditional medicines must be protected from future losses. CONCLUSIONS: Our findings provide insights for future research aimed at exploiting the rich phytochemical diversity in traditional medicine and promote its use in modern lifestyles. Effective assessment and management of plant resources will lead to their application for the improvement of dietary diversity, nutrition, and health care.

Small Cell Carcinoma of the Ureter With Early Recurrence and Multiple Metastases Shown on 18 F-FDG PET/CT.

ABSTRACT: Primary small cell carcinoma of the ureter is an extremely rare malignancy with a poor prognosis. We present rare interesting 18 F-FDG PET/CT images of primary small cell carcinoma of the ureter in a 37-year-old man with early recurrence and multiple metastases 2 months after laparoscopic left nephroureterectomy and pelvic tumor resection. PET/CT showed high FDG-avid lesions in the pelvis, peritoneum, the left posterior wall of the bladder, and in the right lung, providing important value in the detection of recurrence and systemic metastases.

circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6.

BACKGROUND: Gastric cancer (GC) is the most common cancer globally. Recent research has suggested that circular RNAs (circRNAs) play crucial roles in GC tumorigenesis and progression. The present study is performed to clarify the possible mechanism of circRNA has_circ_0006089 (circ_0006089) in GC. METHODS: The differentially expressed circRNAs were screened out by analyzing the dataset GSE83- 521. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0006089, miR-515-5p and CXCL6 expression levels in GC tissues and cell lines. CCK-8, BrdU and Transwell assays were adopted to examine the biological function of circ_0006089 in GC cells. The interaction between miR-515-5p and circ_0006089, as well as between CXCL6 and miR-515-5p, was confirmed through bioinformatics, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and RNA pull-down assay. RESULTS: Circ_0006089 was significantly upregulated in GC tissues and cells, and miR-515-5p was remarkably downregulated. After knocking down circ_0006089 or overexpressing miR-515-5p, the growth, migration and invasion of GC cells were markedly reduced. In terms of mechanism, miR-515- 5p was verified to be the target of circ_0006089, and CXCL6 was validated as miR-515-5p's downstream target gene. Inhibiting miR-515-5p reversed the inhibitory effect knocking down circ_0006089 had on GC cell proliferation, migration and invasion. CONCLUSION: Circ_0006089 facilitates the malignant biological behaviors of GC cells via the miR-515- 5p/CXCL6 axis. Circ_0006089 can probably act as one of the important biomarkers and therapeutic targets in GC treatment strategies.

TFEB Rearranged Renal Cell Carcinoma: Pathological and Molecular Characterization of 10 Cases, with Novel Clinical Implications: A Single Center 10-Year Experience.

To report our experience with the cases of TFEB rearranged RCC, with particular attention to the clinicopathological, immunohistochemical and molecular features of these tumors and to their predictive markers of response to therapy. We have retrieved the archives of 9749 renal cell carcinomas in the Institute of Urology, Peking University and found 96 rearranged RCCs between 2013 and 2022. Among these renal tumors, ten cases meet the morphologic, immunohistochemical and FISH characterization for TFEB rearranged RCC. The 10 patients' mean and median age is 34.9 and 34 years, respectively (range 23-55 years old), and the male to female ratio is 1:1.5. Macroscopically, these tumors generally have a round shape and clear boundary. They present with variegated, grayish yellow and grayish brown cut surface. The average maximum diameter of the tumor is 8.5 cm and the median 7.7 (ranged from 3.4 to 16) cm. Microscopically, the tumor is surrounded by a thick local discontinuous pseudocapsule. All tumors exhibit two types of cells: voluminous, clear and eosinophilic cytoplasm cells arranged in solid sheet, tubular growth pattern with local cystic changes, and papillary, pseudopapillary and compact nested structures are also seen in a few cases. Non-neoplastic renal tubules are entrapped in the tumor. A biphasic "rosette-like" pattern, psammomatous calcifications, cytoplasmic vacuolization, multinucleated giant cells and rhabdomyoid phenotype can be observed in some tumors. A few tumors may be accompanied by significant pigmentation or hemorrhage and necrosis. The nucleoli are equivalent to the WHO/ISUP grades 2-4. All tumors are moderately to strongly positive for Melan-A, TFEB, Vimentin and SDHB, and negative for CK7, CAIX, CD117, EMA, SMA, Desmin and Actin. CK20 and CK8/18 are weakly positive. In addition, AE1/AE3, P504s, HMB45 and CD10 are weakly moderately positive. TFE3 is moderately expressed in half of the cases. PAX8 can be negative, weakly positive or moderately-strongly positive. The therapy predictive marker for PD-L1 (SP263) is moderately to strongly positive membranous staining in all cases. All ten tumors demonstrate a medium frequency of split TFEB fluorescent signals ranging from 30 to 50% (mean 38%). In two tumors, the coincidence of the TFEB gene copy number gains are observed (3-5 fluorescent signals per neoplastic nuclei). Follow-up is available for all patients, ranging from 4 to 108 months (mean 44.8 and median 43.4 months). All patients are alive, without tumor recurrences or metastases. We described a group of TFEB rearranged RCC identified retrospectively in a large comprehensive Grade III hospital in China. The incidence rate was about 10.4% of rearranged RCCs and 0.1% of all the RCCs that were received in our lab during the ten-year period. The gross morphology, histological features, and immunohistochemistry of TFEB rearranged RCC overlapped with other types of RCC such as TFE3 rearranged RCC, eosinophilic cystic solid RCC, or epithelioid angiomyolipoma, making the differential diagnosis challenging. The diagnosis was based on TFEB fluorescence in situ hybridization. At present, most of the cases reported in the literature have an indolent clinical behavior, and only a small number of reported cases are aggressive. For this small subset of aggressive cases, it is not clear how to plan treatment strategies, or which predictive markers could be used to assess upfront responses to therapies. Between the possible options, immunotherapy currently seems a promising strategy, worthy of further exploration. In conclusion, we described a group of TFEB rearranged RCC identified in a large, comprehensive Grade III hospital in China, in the last 10 years.

Alpha-fetoprotein-elevated postpubertal testicular teratoma with retroperitoneal metastasis on 18F-FDG PET/CT: case report and literature review.

Postpubertal testicular teratoma exhibits malignant biological behavior and has metastatic potential. We report a case of a 17-year-old patient diagnosed with postpubertal testicular teratoma with massive retroperitoneal metastasis. The pathological examination revealed a mature teratoma without any other components. However, the patient had a significantly increased level of AFP, and 18F-FDG PET/CT showed the retroperitoneal metastasis had increased FDG uptake, with a SUVmax of 15.6, suggesting the coexistence of other germ cell tumor components, and the patient might have a poor prognosis. After resection of the retroperitoneal tumor, PET/CT further revealed multiple abdominal and pelvic metastases, with a SUVmax of 22.5. Therefore, the patient received a cycle of chemotherapy and follow-up PET/CT imaging showed the achievement of complete metabolic response after the treatment. In this case, PET/CT played a crucial role in detecting metastasis, compensating for the limitations of pathological sampling, thus establishing a definitive diagnosis and predicting prognosis. And it was evident that PET/CT also has the advantage of evaluating therapeutic efficacy.

Multimodality imaging of Xp11.2 translocation/TFE3 gene fusion associated with renal cell carcinoma: a case report.

Background: Xp11.2 translocation/TFE3 gene fusion associated with renal cell carcinoma (Xp11.2 RCC) exhibits unique biological characteristics and is associated with an increased incidence of tumor thrombosis, lymph node metastasis, and advanced disease stages. Multimodality imaging, including US, contrast-enhanced CT, multi-parametric MRI, and 18F-FDG PET/CT plays a crucial role in the preoperative diagnosis and differentiation of renal tumors. Case report: A 15-year-old female presented with lumbar pain worsened, and developed persistent painless hematuria. The CT attenuation values of the scan without contrast, corticomedullary phase, nephrographic phase, and delayed phases were 35 HU, 83 HU, 82 HU, and 75 HU, respectively. The solid component of the mass displayed heterogeneous marked enhancement. Furthermore, MRU indicated that the lesion involved the cortical medulla and infringed on the renal sinus fat. The lesion appeared isosignal in T1WI, slightly low signal in T2WI, and slightly high signal in DWI. The degree of enhancement in the three phases of enhancement scan was lower than that in the renal parenchyma, and hemorrhage and necrosis were observed within the internal part of the lesion. To further clarify the staging, the patient underwent 18F-FDG PET/CT. PET/CT images showed multiple irregular occupancies in the right kidney with unclear borders, showing a heterogeneous increase in 18F-FDG uptake, with SUVmax values ranging from 2.3 to 5.2 in the routine imaging phase (60 min post-injection), compared to SUVmax values ranging from 2.8 to 6.9 in the delayed imaging phase (160 min post-injection). Additionally, multiple enlarged and fused lymph nodes were observed in the medial part of the right kidney and the retroperitoneum, exhibiting a heterogeneous increase in 18F-FDG uptake, with SUVmax values ranging from 4.1 to 8.7 in the routine imaging phase, compared to SUVmax values ranging from 4.4 to 9.1 in the delayed imaging phase. The postoperative pathology, immunohistochemistry, and molecular analysis of histiocytes were consistent with a diagnosis of Xp11.2 RCC. One month after surgery, enhanced-CT examination of the patient revealed lung metastasis, peritoneal metastasis, and multiple lymph node metastases throughout the body, with an overall survival of 16 months. Conclusion: Xp11.2 RCC exhibits unique biological characteristics and is associated with an increased incidence of tumor thrombosis, lymph node metastasis, and advanced disease stages. Long-term follow-up is essential to monitor the likelihood of recurrence and metastasis. 18F-FDG PET/CT examination can comprehensively visualize the lesion's location and extent, providing a basis for clinical tumor staging and aiding in treatment monitoring and follow-up. To address the limitations of FDG, the utilization of specific tracers designed for RCC or tracers that are not excreted via the urinary system would be ideal. Further advancements in molecular imaging technologies and the development of novel tracers hold great promise in advancing the diagnosis and management of RCC, ultimately contributing to better patient outcomes and overall disease management.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.

H-ras mutation detection in bladder cancer by COLD-PCR analysis and direct sequencing.

OBJECTIVE: A sensitive mutation detection method called co-amplification at lower denaturation temperature-polymerase chain reaction (COLD-PCR) was applied to improve the detection frequencies of expressive mutations in the H-ras gene, including exons 1 and 2, in a group of Chinese patients diagnosed with bladder cancer. MATERIALS AND METHODS: The expressive mutations in the H-ras gene in 86 fresh tissues of human bladder cancer were identified by COLD-PCR or conventional PCR, followed by direct sequencing. RESULTS: A high frequency of silent mutations of 29.1% (25 of 86) in exon 1 (c.81T>C, H27H) and activating mutations of 8.1% (7 of 86) were detected by COLD-PCR, yielding a 36% improvement in mutation detection compared with conventional PCR. No significant association was shown between activating mutations and clinicopathologic parameters, but the frequencies of silent mutations in recurrent tumors were higher than those in primary tumors (p = 0.034). CONCLUSIONS: COLD-PCR is a highly sensitive, reliable, and convenient clinical assay for mutation detection. The adoption of the method is straightforward and requires no additional reagents or instruments. Silent mutations might be important genomic alterations in bladder cancer, and play a role in bladder cancer recurrence.

Diagnostic performance and prognostic value of preoperative 18F-FDG PET/CT in renal cell carcinoma patients with venous tumor thrombus.

BACKGROUND: To observe the diagnostic efficacy of preoperative fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) upon venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC), and investigate the prognostic value of imaging parameters integrated with clinicopathological characteristics in patients with VTT after nephrectomy with tumor thrombectomy. METHODS: Patients with newly diagnosed RCC who underwent 18F-FDG PET/CT were reviewed retrospectively. The diagnostic efficacy of 18F-FDG PET/CT in VTT was analyzed. Logistic regression analysis was carried out to identify the clinical variables and PET/CT variables (including maximum standardized uptake value (SUVmax) of primary tumor, VTT SUVmax and primary tumor size) for differentiating early VTT (Mayo 0-II) from advanced VTT (Mayo III-IV). Cox proportional hazard analyses were used to evaluate clinicopathological factors and PET/CT factors (including distant metastasis, primary tumor SUVmax, VTT SUVmax and primary tumor size) for disease-free survival (DFS) in patients with VTT after operation. RESULTS: A total of 174 eligible patients were included in this study, including 114 men (65.5%) and 60 women (34.5%), with a median age of 58 years (range, 16-81 years). The distribution of pathological tumor stage (T stage) was 56 (T1), 17 (T2), 95 (T3), and 6 cases (T4), respectively. According to WHO/ISUP grade, except for 4 cases of chromophobe cell RCC, there were 14 patients (8.0%) of grade 1, 59 patients (33.9%) of grade 2, 74 patients (42.5%) of grade 3 and 23 patients (13.2%) of grade 4. The median maximum diameter of the primary tumor on PET/CT was 7.3 cm (5.0-9.5 cm). The distal metastasis was observed in 46 patients (26.4%). Sixty-one cases (35.1%) were confirmed with VTT by pathology. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT imaging were 96.7, 99.1, 98.3, 98.3, and 98.2%, in detecting VTT, respectively, and 70.0, 100.0, 94.9, 100.0, and 94.2%, in evaluating the level of VTT, respectively. Elevated VTT SUVmax (≥5.20) could significantly distinguish the early VTT group and advanced VTT group (P = 0.010). In the prognosis analysis, elevated VTT SUVmax (≥4.30) (P = 0.018, HR 3.123, 95% CI 1.212-8.044) and distant metastasis (P = 0.013, HR 3.344, 95% CI 1.293-8.649) were significantly independent predictors for DFS. CONCLUSION: Preoperative 18F-FDG PET/CT has a high diagnostic efficacy in detecting VTT and evaluating its level in RCC patients. Those patients with elevated VTT SUVmax should be carefully monitored to detect the possibility of disease progression after operation.