Clinical Medicine Insights-Oncology最新文献

Background: Immunohistochemical results are of vital importance in the classification of patients with breast cancer into subgroups and in treatment decision-making at every stage. However, differences can occur in biopsy results obtained from the same patient. In our study, we aimed to investigate the importance of pathological examination, which is a possible reason for the differences in patients' immunohistochemistry results.

Methods: For this purpose, patients were divided into 3 groups. The differences in estrogen receptor, progesterone receptor, HER2, and Ki-67 were examined between the following groups: patients who received neoadjuvant chemotherapy and then underwent surgery (41 patients), patients who underwent surgery without chemotherapy (50 patients), and the same specimen from a different center and our center (21 patients).

Results: The pathological discordance rates were 34.1% in the neoadjuvant chemotherapy group, 28% in the surgery without chemotherapy group, and 38.1% in the comparison between our institution and an external center, with no statistically significant difference across the 3 groups (P = .667). When examining the changes within each group, statistically significant differences were found in HER2 (P = .002) for the tru-cut biopsy surgery group and Ki-67 (P = .025) for the group comparing our center to an external center.

Conclusions: As a result, it was considered that one of the important reasons for the immunohistochemical differences in breast biopsies, which is a known fact, is the evaluating center and pathologist.

Background: Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer typically diagnosed at advanced stages, limiting treatment options and reducing survival rates. Targeted therapy presents a promising strategy to improve outcomes. This study aims to identify novel molecular biomarkers influencing ICC development and explore their roles in tumor progression.

Methods: Data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed using weighted gene co-expression network analysis (WGCNA) to identify genes related to tumor metastasis and recurrence. Survival analysis and gene set enrichment analysis (GSEA) assessed the relationship between gene expression and survival, as well as associated signaling pathways. Cellular experiments, including small interfering RNA (siRNA) knockdown, cell viability assays, Transwell migration assays, and flow cytometry, were performed.

Results: The Kaplan-Meier analysis showed that ICC patients with high N-acetyltransferase 2 (NAT2) expression had significantly shorter survival times than those with low expression (P < .001). Gene set enrichment analysis revealed enrichment of MYC and MTORC1 pathways, linked to tumor proliferation, and E2F and G2M pathways, which regulate the cell cycle, in high NAT2 expression samples (P < .01). The NAT2 knockdown reduced RBE cell proliferation (P < .001) and increased late apoptosis (P < .001). Immunofluorescence analysis showed increased Bax and Caspase-3 expression and decreased BCL-2 expression (P < .05), supporting NAT2's role in regulating ICC cell apoptosis.

Conclusion: NAT2, a novel therapeutic target, holds significant potential to improve the prognosis of ICC patients.

The eradication of tumors remains a critical and challenging issue in medical research. Exosomes (EXOs) derived from various sources have garnered increasing attention in the field of tumor therapy. Among these, cord blood (CB)-derived EXOs may offer unique advantages in combating tumors due to the distinctive properties of CB. This narrative review examines the current application status of CB-derived EXOs in tumor prevention and treatment: in the context of tumor treatment, it focuses on their direct therapeutic application and their use as drug carriers; regarding tumor prevention, it explores their application in cancer vaccines. In addition, it also reviews the specific components of CB from which these EXOs are derived, their particle sizes, characteristic proteins, and the types of tumors to which they have been primarily applied for prevention and treatment. In conclusion, we believe that CB-derived EXOs hold substantial potential for effective tumor prevention and treatment and are likely to emerge as a prominent area of research in the future.

Background: This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.

Methods: We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, in vitro siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.

Results: Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, P < .05; GSE48075: HR > 1.5, P = .07; GSE169455: HR > 2.8, P < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.

Conclusion: This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.

Background: This study aimed to determine the prognostic effect of the serum vitamin B12 level/CRP ratio (BCR) on patients diagnosed with solid cancer.

Methods: Patients >18 years diagnosed with solid cancer were included in the study, the data of the patients were retrospectively examined, and the cut-off values for BCR were determined using receiver operating characteristic (ROC) analysis. Accordingly, grouping was performed, appropriate statistical analyses were performed, and P < .05 was accepted as the significance limit value.

Results: The median age of the 344 patients included in the study was found to be 60.9 (range: 27-88) years. Around 56.6% (n = 174) of the patients had nondistant metastatic group and 49.4% (n = 170) had metastatic group. The median follow-up period of the patients was found to be 46.8 (range: 4-63) months. In the metastatic group, mortality was statistically significantly 2.1 times higher in those with a BCR cut-off value <3.5 (95% confidence interval [CI]; 1.4-3.2, P < .001). In the nonmetastatic group, mortality was statistically significantly twice higher in those with a BCR cut-off value <3.8 (95% CI; 1.4-3.3, P < .001). In addition, mortality was statistically significantly higher in high-risk patients in the nonmetastatic group (63.8% (n = 188) vs 45.5% (n = 156) (P < .001). The mOS period for patients in the high-risk group was 42.8 ± 1.4 (95% CI: 40.1-45.5) months, the mOS period for patients in the low-risk group was 51.5 ± 1.3 (95% CI: 49.0-54.0) months, and the mOS period for the entire group was 46.8 ± 1.0 (95% CI: 44.8-48.7) months (P < .001).

Conclusıons: In conclusion, our study has shown that BCR, which has not been reported in the literature to date, is one of the cheapest and easily accessible inflammation markers that can determine prognosis in cancer patients.

Background: Cribriform pattern 4 (CP4) is an aggressive variant in prostate cancer linked to worse clinical outcomes, including biochemical recurrence, metastases, and prostate cancer-specific mortality. However, its prognostic significance across age groups remains unclear. This study investigates whether the impact of CP4 on progression-free survival (PFS) differs by age in patients undergoing radical prostatectomy (RP).

Methods: This retrospective analysis used patient data from the TCGA database, evaluating patients who underwent RP stratified by CP4 status. The primary outcome was PFS, defined as the time from RP to biochemical recurrence, radiographic progression, or death from any cause. Multivariable Fine-Gray competing risk regression analyses assessed the association between CP4 and PFS, adjusting for preoperative prostate-specific antigen (PSA), Gleason score, tumor stage, and surgical margin status. An interaction term between age (dichotomized at 60 years to facilitate clinical interpretation and applicability, approximating the cohort median age of 61 years [interquartile range = 56-66]) and CP4 status was included in the analysis.

Results: Of 431 patients, CP4 was present in 134 (31%). In multivariable analysis, CP4 was associated with significantly worse PFS in patients older than 60 years (adjusted hazard ratio [AHR]: 1.99, 95% confidence interval [CI]: 1.01-3.92, P < .001), but not in younger patients (⩽60 years; AHR: 1.00, 95% CI: 0.49-2.04, P = .997). Adjusted 5-year PFS was significantly lower in older CP4-positive patients (50.8%, 95% CI: 33.0%-78.2%) compared with older CP4-negative patients (74.6%, 95% CI: 63.6%-87.6%; P < .001).

Conclusion: CP4 strongly predicts reduced PFS in patients above 60 years but not younger patients, suggesting that age may influence the clinical impact of CP4. These findings support age-specific risk stratification in CP4-positive prostate cancer. Prospective studies are needed to validate results and explore tailored treatment strategies based on age.

Background: Our aim was to demonstrate the efficacy and safety of pembrolizumab monotherapy as second-line treatment in Vietnamese nonsmall cell lung cancer (NSCLC) patients.

Methods: We performed a single-center retrospective study of patients with advanced NSCLC who received pembrolizumab as second-line therapy at the Vietnam National Cancer Hospital between January 2017 and October 2023. The primary endpoints were overall survival (OS) and tumor response.

Results: A total of 52 patients were included. Adenocarcinoma was observed in 43 of 52 cases (82.7%), and 40.4% of patients had PD-L1 expression in at least 50% of tumor cells. Median body weight was 57 kg (range, 45-80), and 73.1% of patients received pembrolizumab at a dose of 100 mg/3 weeks, with a median dose of 1.9 mg/kg/3-weeks (range, 1.3-4.3). The overall response rate and disease control rate were 26.9% and 51.9%, respectively. Median PFS was 6.5 months (95% CI, 3.3-9.7), and 1-year and 2-year PFS rates were 28.5% and 15.9%, respectively. Median OS was 12.0 months (95% CI, 9.8-14.2); 1-year, 2-year, and 3-year OS rates were 53.1%, 22.3%, and 8.5%, respectively. ECOG status and number of organs metastases were significantly associated with PFS and OS in the multivariate analysis. No adverse events of grades 3 to 4 were reported during the treatment.

Conclusions: Second-line pembrolizumab has a good disease control rate and prolonged survival and is a viable option for the treatment of Vietnamese NSCLC patients. Further clinical studies are necessary to determine the effectiveness of administering a low dose of pembrolizumab in this setting, particularly in Asian population.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the current standard for locally advanced rectal cancer. This study aimed to evaluate the need for adjuvant chemotherapy and clinical outcomes in patients with ypT3-4N0M0 rectal cancer.

Methods: This is a retrospective cohort study. We reviewed the patients with locally advanced rectal cancer who had undergone radical resection after nCRT between 2010 and 2016. A total of 69 patients with ypT3-4N0M0 rectal cancer were included. The prognostic factors affecting disease-free and overall survival were analyzed.

Results: With clinical stage II-III and pathological stage II disease, the overall survival in the adjuvant chemotherapy group (n = 38) was better than that of the group without adjuvant chemotherapy (n = 31) (86.8%, vs 74.2%, P = 0.016). The disease-free survival was better in 2 groups, but the difference was not statistically significant (73.7%, vs 67.4%, P = 0.193).

Conclusions: In patients with clinical stage III rectal cancer downstaged to ypStage II after nCRT and TME, adjuvant chemotherapy may improve overall survival. nCRT combined with postoperative adjuvant chemotherapy remains an effective strategy for patients unsuitable for complete total neoadjuvant therapy protocols.

Background: Euthyroid sick syndrome (ESS) is associated with cancer staging and influences prognosis in patients with lung and various other solid tumors. Although previous studies have examined the association between ESS and factors such as age, body mass index, Eastern Cooperative Oncology Group performance status (ECOG PS), hemoglobin (Hb), and acute-phase reactants in patients with solid cancers, its relationship with 25-hydroxyvitamin D [25(OH)D] remains unclear. In this study, we investigated the factors associated with ESS and explored the relationship between 25(OH)D levels and ESS in hospitalized patients with solid cancers (HSC).

Methods: This retrospective study included 105 patients with HSC. Laboratory parameters were assessed using the initial blood samples collected upon hospitalization. Patients with low fT3, normal or low fT4, and normal thyrotropin (TSH) levels were classified as having ESS.

Results: The overall prevalence of ESS was 37.1%. Among HSC receiving supportive care, the ESS rate was 40.3%, whereas it was lower-28.6%-in those hospitalized for chemotherapy. A statistically significant association was observed between ESS and ECOG PS, C-reactive protein (CRP), and Hb levels. Specifically, a poor ECOG PS (P < .001), low Hb levels (P = .001), and elevated CRP levels (P < .001) were significantly associated with ESS. However, no significant relationship was found between 25(OH)D levels and ESS (P = .118).

Conclusion: Euthyroid sick syndrome may be relatively common among patients with HSC and is more frequently observed in those hospitalized for supportive care. In this patient population, ESS was significantly associated with ECOG PS, Hb, and CRP; however, no significant association was identified between ESS and 25(OH)D.

Background: To evaluate the efficacy and safety of cisplatin combined with alternating temozolomide (TMZ) for recurrent high-grade glioma, as current treatments lack standardized protocols and predictive markers.

Methods: This study evaluated cisplatin (20 mg/m² IV, days 1-3) and TMZ (125 mg/m² orally, days 1-7 and 15-21) in 35 patients, using the RANO criteria with 6-month progression-free survival (PFS-6) as the primary endpoint. The Kaplan-Meier analysis was applied for survival, and tumor molecular profiles were retrospectively assessed.

Results: A median follow-up time was 61.2 months. The PFS-6 rate was 45.2%, and the median time to progression was 5.07 months. Four patients showed partial response, 16 had stable disease, and 11 had disease progression, with predominantly grade I to II toxicities. Low CD8+ tumor-infiltrating lymphocytes (TILs) correlated with improved disease control (P = .031). Data from the CGGA showed that low CD8+ TILs were associated with better survival, while high CD8+ TILs indicated increased immune response and higher immune checkpoint expression, including programmed death 1 (PD-1).

Conclusions: The cisplatin plus alternating TMZ regimen is feasible and safe for recurrent high-grade gliomas, with low CD8+ TILs potentially predicting favorable responses.