Oncology最新文献

Introduction: As the primary members of the deubiquitinase family, ubiquitin-specific proteases can regulate the efficacy of immunotherapy and mediate immune evasion. However, further research is needed to explore the influence of USP52 on the prognosis of colorectal cancer (CRC), the tumor immune microenvironment, and therapeutic response.

Methods: The differential expression of USP52 between CRC and normal tissues was analyzed using multiple public databases. The relationship between USP52 with the prognosis and clinicopathological characteristics of CRC patients was evaluated, and a nomogram was constructed to predict patient survival based on USP52 expression. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP52 in CRC. The impact of USP52 on the tumor microenvironment (TME) was estimated. Moreover, the effect of USP52 on the response to immunotherapy and chemotherapeutic drugs in CRC was investigated. Finally, the correlation between tumor mutation burden (TMB)/microsatellite instability (MSI) status and USP52 was explored.

Results: The expression of USP52 was markedly upregulated in CRC, correlating with a poor prognosis in patients. GSVA uncovered a strong association between high USP52 and immune suppression. Furthermore, high USP52 was found to be correlated with a non-inflamed TME, resulting in reduced immune cell infiltration levels. Additionally, it was observed that patients with high USP52 exhibited low sensitivity to both immunotherapy and chemotherapeutic drugs. Lastly, high USP52 was negatively associated with high TMB and MSI.

Conclusion: This study revealed the significance of USP52 in TME, efficacy of therapy, and clinical prognosis in CRC, offering novel insights for the therapeutic advancements in CRC.

Introduction: Identifying accurate biomarkers for predicting response to chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC) is a critical challenge. The protein SIRT1, recognized for its implications in longevity, has been associated with tumor promotion in ESCC. However, data regarding its correlation with CRT sensitivity remain unreported. Therefore, in this study, we aimed to investigate the relationship between SIRT1 expression and CRT sensitivity and concurrently assess the effect of SIRT1 knockdown on CRT sensitivity in ESCC.

Methods: This study included 73 patients who underwent radical esophagectomy after CRT. SIRT1 expression in pre-treatment endoscopic biopsies was assessed through immunostaining, followed by a comparative analysis of CRT effects on surgical specimens. Small interfering RNA was used to attenuate SIRT1 expression in TE5 and TE10 cells, which were then subjected to cisplatin treatment at varying doses and concentrations and irradiation with X-rays, respectively.

Results: High SIRT1 tissue expression was significantly associated with CRT resistance. Multivariate analysis identified high SIRT1 expression as an independent biomarker for poor CRT response. In TE-5 and TE-10 cells, SIRT1 knockdown significantly decreased cell viability and increased sensitivity to cisplatin and radiation treatment compared to that of the negative control.

Conclusion: Our study results demonstrate the potential of SIRT1 as a predictive biomarker for CRT response in ESCC, highlighting the heightened sensitivity to CRT upon the transcriptional inactivation of SIRT1. Targeting SIRT1 emerges as a promising strategy for enhancing the efficacy of CRT for ESCC.

Introduction: Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients.

Materials and methods: The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated.

Results: In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01).

Conclusion: The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.

Introduction: In silico tools capable of predicting the functional consequences of genomic differences between individuals, many of which are AI-driven, have been the most effective over the past two decades for non-synonymous single nucleotide variants (nsSNVs). When appropriately selected for the purpose of the study, a high predictive performance can be expected. In this feasibility study, we investigate the distribution of nsSNVs with an allele frequency below 5%. To classify the putative functional consequence, a tier-based filtration led by AI-driven predictors and scoring system was implemented to the overall decision-making process, resulting in a list of prioritised genes.

Methods: The study has been conducted on breast cancer patients of homogeneous ethnicity. Germline rare variants have been sequenced in genes that influence pharmacokinetic parameters of anticancer drugs or molecular signalling pathways in cancer. After AI-driven functional pathogenicity classification and data mining in pharmacogenomic (PGx) databases, variants were collapsed to the gene level and ranked according to their putative deleterious role.

Results: In breast cancer patients, seven of the twelve genes prioritised based on the predictions were found to be associated with response to oncotherapy, histological grade, and tumour subtype. Most importantly, we showed that the group of patients with at least one rare nsSNVs in cystic fibrosis transmembrane conductance regulator (CFTR) had significantly reduced disease-free (log rank, p = 0.002) and overall survival (log rank, p = 0.006).

Conclusion: AI-driven in silico analysis with PGx data mining provided an effective approach navigating for functional consequences across germline genetic background, which can be easily integrated into the overall decision-making process for future studies. The study revealed a statistically significant association with numerous clinicopathological parameters, including treatment response. Our study indicates that CFTR may be involved in the processes influencing the effectiveness of oncotherapy or in the malignant progression of the disease itself.

Introduction: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients.

Methods: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated.

Results: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis.

Conclusion: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.

Introduction: This study aimed to show the relationship between the serum uric acid level measured at diagnosis and the BRAF mutation status in the primary tumor tissue in patients with metastatic colorectal cancer.

Methods: In this retrospective cross-sectional study, 264 patients (64% male) whose serum uric acid level was measured at the time of diagnosis and whose BRAF mutation status in the primary tumor was determined were included.

Results: The BRAF mutation rate was 14% (n = 37). The median serum uric acid levels of all patients were 6.9 mg/dL (25%, 75% percentile range 3.7, 8.2). The serum uric acid level cut-off value was 6.6 mg/dL. Sensitivity and specificity for BRAF mutated patients were 84% and 27%, respectively. These rates were calculated as 85% and 70% in BRAF-mutated patients aged 65 and over. There was a significant correlation between BRAF mutation and high serum uric acid level, female gender, tumor located in the ascending colon, and multiple metastatic sites. The independent factors affecting BRAF mutation were age 65 and over, tumor in the ascending colon, and high serum uric acid level.

Conclusion: As a result, we concluded that high serum uric acid level measured during diagnosis in metastatic colorectal cancer is an accessible and economical biomarker that can predict BRAF mutation in patients aged 65 and over.

Introduction: Adolescents and young adults (AYAs) diagnosed with chronic myeloid leukemia (CML) constitute a significant demographic group, particularly in regions with youthful populations like Qatar. Despite the global median age of CML diagnosis being 65 years, Qatar's age distribution reflects a younger cohort. This study investigates whether AYAs with CML exhibit distinct clinicopathological characteristics or outcomes compared to older age groups.

Methods: A total of 224 CML patients were enrolled, including 114 AYAs (defined as ages 15 through 39). Demographic and clinical parameters, including gender, BMI, BCR-ABL1 transcript type, white blood cell (WBC) count, hemoglobin level, platelet count, and spleen size, were compared between AYAs and older patients. Prognostic scoring systems (Sokal, Hasford, EUTOS, and ELTS) and molecular response rates (MMR and DMR) were also evaluated.

Results: AYAs demonstrated higher WBC counts at diagnosis (median 142.3 vs. 120; p = 0.037) and lower hemoglobin levels (10.5 vs. 11.40; p = 0.004) compared to older patients. Spleen size was significantly larger in AYAs (18.8 vs. 15.5; p = 0.001). While AYAs showed better prognostic scores by Sokal and Hasford criteria, EUTOS and ELTS scores indicated comparable risk stratification. However, AYAs exhibited lower rates of MMR (56.7 vs. 73.4%; p = 0.016) and achieved MMR at a slower pace (median time 130 vs. 103 months; p = 0.064). Similarly, the percentage of DMR was lower in AYAs (37.1 vs. 46.8%; p = 0.175).

Conclusion: Despite their younger age, AYAs with CML displayed poorer prognoses compared to older patients. These findings underscore the importance of tailored management strategies for AYAs with CML to optimize outcomes in this distinct patient population.

Key point: AYAs are underrepresented in CML studies and risk scores, so this is the focus of this study.

Introduction Retinoblastoma treatment and follow-up is complex and varies between patients. Pathways of care can enhance quality of care, patient outcomes, safety, satisfaction, and resource optimization. Developing a pathway of care for retinoblastoma was identified as a top research priority by the retinoblastoma community. This study aimed to co-design and pilot a pathway of care called the "Retinoblastoma Journey Map" tailored for caregivers of newly diagnosed children with retinoblastoma. Methods A working group of patients, health professionals and researchers used human-centred design to ideate, prototype and refine the Retinoblastoma Journey Map. Caregivers of affected children were recruited to use and evaluate the Map. Mixed-methods data was collected on feasibility, acceptability, usability and perceived impact on communication, self-efficacy, anxiety, depression, and the quality of physician-patient interaction. Results The Retinoblastoma Journey Map consisted of an illustrated roadmap with 25 child-friendly stickers covering clinical treatment, medical education and milestones. Quantitative analysis revealed that the Map was feasible, acceptable, and usable; however, no significant effect on communication, self-efficacy, anxiety, depression or quality of physician-patient interaction was observed. Qualitative analysis identified 6 themes: Primary Use, Challenges, Impact, Limitations, Feasibility, Acceptability and Usability, and Unmet Needs. Conclusion A pathway of care for retinoblastoma, co-designed by researchers, health professionals and patients, was usable, acceptable, and feasible by caregivers of children with retinoblastoma. While significant effects on communication and physician-patient interaction were not observed, 'legacy building' - documentation of the pathway of care by families for later education of their child - emerged as an unanticipated yet important use of the Retinoblastoma Journey Map.

Introduction: Anaplastic lymphoma kinase (ALK) has been to be involved in the uptake and regulation of dopamine 2 receptor (D2R), a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures.

Methods: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined high-level group term (HLGT): "Seizures (incl. subtype)" including high-level term (HLT): "seizures and seizure disorders NEC." This study used the information component (IC), a signal score, as a Bayesian statistical method for disproportionality analysis. The signal detection criteria used in this study were the same as those reported previously: a lower limit of 95% credible interval (CrI) for IC >0.

Results: The signal scores of '"seizures and seizure disorders not elsewhere classified (NEC)" "for each ALK inhibitor were crizotinib (IC: -0.00052, 95% CrI: -0.38-0.27), ceritinib (IC: 1.18, 95% CrI: 0.68-1.54), alectinib (IC: 0.68, 95% CrI: 0.19-1.02), brigatinib (IC: 1.04, 95% CrI: 0.32-1.54), and lorlatinib (IC: 0.82, 95% CrI: 0.11-1.32). On the other hand, "generalized tonic-clonic seizures," "partial simple seizures NEC," "absence seizures," and "partial complex seizures" had no or few reported cases, and no signal was detected.

Conclusion: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures.