Translational cancer research最新文献

Background: Glioma is a primary malignant brain tumor with a poor prognosis. Glioma-related biomarkers need to be identified to enable the personalized treatment of and predict the prognosis of glioma patients. Cuproptosis is an unusual mechanism of cell death, and is closely associated with disease progression and the immune-microenvironment of the tumor. However, the function of cuproptosis in glioma is still unclear, therefore the aim of this study was to investigate the role of cuproptosis-related genes in gliomas.

Methods: We examined the relationship between cuproptosis and glioma using the clinical and expression data of glioma tumors from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA).

Results: First, we determined the rate of somatic mutations and copy number variations (CNVs) of 51 copper homeostasis-related genes and studied their correlation with prognosis. We then identified three molecular subgroups of copper homeostasis-related genes linked to prognosis. We discovered that different subgroups had distinct immune and biological features. We then developed a prognostic model by least absolute shrinkage and selection operator (LASSO) regression that comprised four cuproptosis-related genes; that is, a solute carrier family 31 member A1 (SLC31A1), microtubule-associated protein tau (MAPT), ATPase beta (ATP7B), and six-transmembrane epithelial antigen of prostate 3 (STEAP3). This model was found to have strong prognostic ability in the CGGA cohort (P<0.05).

Conclusions: We investigated the function of copper homeostasis-related genes in neuroglioma and their relationship with tumor immunology. Our in-depth analyses revealed that these biomarkers are useful for diagnostic and prognostic purposes and could be used to guide our understanding of the progression of and treatment of glioma tumorigenesis.

Testicular cancer is the most commonly diagnosed cancer among young men in the United States. Seminoma comprises a little over half of all testicular germ cell neoplasms. After radial inguinal orchiectomy, management of seminoma is dictated by tumor stage and risk stratification. Dissemination patterns for metastatic testicular cancer are predictable and reproducible, initially metastasizing to the retroperitoneum before disseminating to the lungs or other viscera. Seminomas are exquisitely sensitive to radiation therapy and platinum-based chemotherapy. Approximately 80-85% of men presenting with early stage (clinical stage I) seminoma will not experience a relapse after radical orchiectomy alone. Therefore, surveillance has been supported by the National Comprehensive Cancer Network (NCCN) guidelines as the preferred management strategy. For those at higher risk of relapse, one or two cycles of single-agent carboplatin or radiation therapy are alternative options to reduce the risk of relapse. For patients with early disseminated seminoma (clinical stage IIA and IIB), radiation therapy or chemotherapy with three cycles of bleomycin, etoposide, cisplatin (BEP) or four cycles of etoposide and cisplatin (EP) are well-established options with excellent cure rates. However, these therapies may be associated with significant long-term toxicities. Primary retroperitoneal lymph node dissection (RPLND) in patients with low-volume metastatic seminoma has recently been evaluated for safety and efficacy in prospective clinical trials. Finally, though the role of surgery in patients with advanced seminoma (clinical stage IIC and III) is limited, a subset of patients with a residual mass following chemotherapy >3 cm suggestive of viable germ cell tumor on imaging may benefit from surgical resection. Herein we review the contemporary indications for surgery and outcomes for men with testicular seminoma.

Background and objective: For patients with resectable renal cell carcinoma (RCC), extirpative surgery with curative intent remains the standard of care. Despite surgical resection, most patients with high-risk features experience disease recurrence. The role of perioperative systemic therapy in the management of these patients' disease remains unclear. Several studies have evaluated the efficacy and safety of tyrosine kinase inhibitors (TKIs); however, most trials have yielded negative results. Adjuvant pembrolizumab demonstrated a disease-free survival benefit in the KEYNOTE-564 trial; however, multiple studies of other immune checkpoint inhibitors (ICIs) in a similar patient population did not yield consistent results. This review summarizes the current evidence for perioperative systemic therapy studies in RCC.

Methods: The PubMed, American Society of Clinical Oncology (ASCO), and clinicaltrials.gov databases were used to retrieve articles published from January 1, 2001 to December 31, 2023 using the following search terms: "adjuvant", "neoadjuvant", "perioperative", "VEGF inhibitors", "immune checkpoint inhibitors", and "renal cell carcinoma". The search was limited to articles published in English.

Key content and findings: We summarize the major perioperative systemic therapy studies in RCC patients and provide an analysis of study outcomes, comparing differences in trial design and patient selection. We also discuss ongoing trials and the emergence of novel biomarkers designed to improve patient selection.

Conclusions: The optimal use of perioperative systemic therapy in high-risk RCC is an area of active investigation. The use of adjuvant TKIs failed to demonstrate a survival benefit and was limited by high rates of toxicity. Several neoadjuvant and adjuvant ICI-based combination studies are being carried out to further improve clinical outcomes. Further studies will be needed to identify effective biomarkers to improve patient selection while avoiding overtreatment.

[This retracts the article DOI: 10.21037/tcr.2019.12.11.].

Background: Myxopapillary ependymoma (MPE) is a rare tumor. Most studies have discussed the clinical symptoms and treatment of individual cases, but limited data are provided on overall survival and its influencing factors. Consequently, we aimed to further explore the epidemiological features of MPE and factors influencing overall survival.

Methods: The cohort study extracted information about all patients diagnosed with intracranial MPE from the Surveillance, Epidemiology, and End Results (SEER) 2004-2015. Epidemiological characteristics and prognostic factors after adjustment for different variables were analyzed. Outcomes were 5- and 10-year overall survival. Univariate and multivariate analyses were conducted using the Cox proportional hazards model, with hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: A total of 1,026 cases were identified in the SEER database. No significant difference was found between the incidence of total MPE and the incidence of non-malignant MPE from 2004 to 2015, and there was no incidence trend. The incidence of MPE was higher among people aged 30-34 and 45-49 years old. In 2005, 2007 and 2011, the incidence of men was greater than that of women (P<0.001). Blacks had a lower incidence than whites in years other than 2007, 2010, and 2013. The older age (older vs. younger: HR =1.081, 95% CI: 1.055-1.107), widowed status (widowed vs. single/unmarried: HR =3.058, 95% CI: 1.282-7.296), no surgery (surgery vs. no surgery: HR =0.283, 95% CI: 0.126-0.635), and radiotherapy (radiotherapy vs. no radiotherapy: HR =4.355, 95% CI: 2.211-8.578) were significantly adverse prognostic factors.

Conclusions: Age, marital status, surgery and radiotherapy are factors influencing the overall survival of MPE patients. Surgery is still the main therapeutic choice, while radiotherapy plays a negative role in the management of MPE. Therefore, prospective research is required to verify and complement our findings for MPE control.

Prostate cancer (CaP) represents a significant cause of cancer-related mortality on a global scale. Low- and middle-income countries (LMIC), particularly those in sub-Saharan Africa (SSA), face a disproportionate burden of this disease. Underlying genetic factors as well as barriers to early diagnosis and treatment lead to overall worse outcomes for CaP patients in SSA compared with the United States (U.S.). The number of available therapies for CaP has exploded over the last decade. Discussion of the potential impact these therapies could have on the current management of patients with metastatic CaP in SSA may help to prioritize goals for making drugs available to more patients. We review U.S. Food and Drug Administration (FDA)-approved treatments for metastatic CaP while acknowledging that many of these treatment regimens may not be feasible in SSA given barriers to medication access, significant follow-up required, and limited technological advancements needed to diagnose and treat. The purpose of this manuscript is to aid readers who may be unfamiliar with the currently approved regimens for CaP in the U.S. to provide information that may aid in prioritization of the available therapies for this cancer in SSA. Given our review of both the treatment of CaP in SSA and current treatment options available in the U.S., abiraterone has demonstrated remarkable benefits in advanced CaP and has been well-tolerated. Abiraterone and prednisone combination therapy has demonstrated significant survival benefit to patients in multiple phase three trials and given it was the first of the newer generation hormone therapies to become available, generic options are available allowing for a cost-effective option for patients. Studies have demonstrated similar efficacy when administering low-dose abiraterone taken with a low-fat meal (compared to full dose taken when fasting), which can lead to cost-savings if the drug is at a lower dose. In conclusion, abiraterone and prednisone can be clinically meaningful for patients in SSA and has a favorable and manageable side effect profile. Additional treatment options also have meaningful benefits; however, the absolute benefit of abiraterone as well as the ease of administration would favor pursuing options to make this or similar newer-generation hormone therapy available to patients in SSA.

Background: OpenAI's ChatGPT is a large language model-based artificial intelligence (AI) chatbot that can be used to answer unique, user-generated questions without direct training on specific content. Large language models have significant potential in urologic education. We reviewed the primary data surrounding the use of large language models in urology. We also reported findings of our primary study assessing the performance of ChatGPT in renal cell carcinoma (RCC) education.

Methods: For our primary study, we utilized three professional society guidelines addressing RCC to generate fifteen content questions. These questions were inputted into ChatGPT 3.5. ChatGPT responses along with pre- and post-content assessment questions regarding ChatGPT were then presented to evaluators. Evaluators consisted of four urologic oncologists and four non-clinical staff members. Medline was reviewed for additional studies pertaining to the use of ChatGPT in urologic education.

Results: We found that all assessors rated ChatGPT highly on the accuracy and usefulness of information provided with overall mean scores of 3.64 [±0.62 standard deviation (SD)] and 3.58 (±0.75) out of 5, respectively. Clinicians and non-clinicians did not differ in their scoring of responses (P=0.37). Completing content assessment improved confidence in the accuracy of ChatGPT's information (P=0.01) and increased agreement that it should be used for medical education (P=0.007). Attitudes towards use for patient education did not change (P=0.30). We also review the current state of the literature regarding ChatGPT use for patient and trainee education and discuss future steps towards optimization.

Conclusions: ChatGPT has significant potential utility in medical education if it can continue to provide accurate and useful information. We have found it to be a useful adjunct to expert human guidance both for medical trainee and, less so, for patient education. Further work is needed to validate ChatGPT before widespread adoption.

Microphthalmia-associated transcription factor family translocation renal cell carcinoma (MiT-tRCC) stands out as a rare subtype of kidney cancer with distinct biological features compared to other kidney cancer subtypes. It encompasses TFE3-rearranged RCC (also known as Xp11 translocation RCC) and TFE-rearranged translocations RCC, although multiple new fusion partners were identified. Traditionally thought to primarily affect children and young adults, more cases of MiT-tRCC are being identified in adults. It was first officially recognized in the 2004 World Health Organization (WHO) renal tumor classification and recently TFE3 (Xp11) rearrangement and TFEB alterations were included in the WHO 2022 "molecularly defined renal carcinomas" as a distinct group. This subtype is distinguished by gene fusions involving the MiT family of transcription factors. Recent strides in diagnostic and molecular sequencing assays have significantly enhanced our comprehension of these tumors, uncovering novel and distinct molecular features. The discovery of novel immune-checkpoint inhibitors and anti-angiogenic targeted therapies has notably broadened the therapeutic options for clear cell RCC. These advancements have prompted the consideration and study of these innovative therapies in translocation RCC. In this review, we offer an overview of translocation RCC and delve into the current strides in the management of this distinctive disease, highlighting the integration of recent breakthroughs in therapeutic approaches.

Background: Alpha-fetoprotein-to-PIVKA-II ratio (APR) may serve as a new marker to predict the grade of differentiation, imaging characteristics, and prognosis of hepatocellular carcinoma (HCC). This study aimed to demonstrate the prognostic significance of high APR for poorly differentiated HCC (PD-HCC), imaging characteristics and overall survival (OS) in patients after intra-arterial therapies.

Methods: Receiver operating characteristic (ROC) curves were constructed and areas under the curve (AUCs) were calculated to evaluate the predictive ability of APR to discriminate subgroup(s) of HCC with good or poor prognosis. Kaplan-Meier survival analysis was performed to evaluate the effect of tumor differentiation and change in APR on overall patient survival.

Results: The cut-off value of APR used in the diagnostic setting was 0.175. Almost all patients in the PD-HCC group (90.9%) had a high APR value, while 100% and 84.2% of well-differentiated and moderately differentiated HCC (WD-HCC and MD-HCC) patients, respectively, had a low APR value (P<0.001). APR had a high sensitivity (91%) and specificity (90%) in differentiating PD-HCCs from WD-HCCs/MD-HCCs (P<0.001). Patients with high APR tended to have large and multiple tumors, vascular invasion and high percentage signal ratio (PSR). OS was slightly shorter in the PD-HCC group and in the high (>0.175) APR group.

Conclusions: This study showed that patients with high APR and those with PD-HCC had a worse prognosis, and APR could be an important non-invasive biomarker for predicting the degree of tumor differentiation, imaging characteristics and patient prognosis.