Clinical Medicine Insights-Oncology最新文献

Background: The DNA methylation statuses of PAX1 and ZNF582 show great promise as biomarkers for the detection of oral squamous cell carcinoma (OSCC). This study aims to investigate the distribution of PAX1 or ZNF582 methylation in the exfoliated oral epithelial cells (OECs) of OSCC.

Methods: Methylation data from 528 tumors and 50 adjacent nontumor tissues were acquired from The Cancer Genome Atlas and analyzed using UALCAN database. Sixty-one OSCC cases from Peking University School and Hospital of Stomatology were included in this study and the exfoliated OECs collected by oral swabs were collected from the cancerous lesion (CL), adjacent normal (AN), and contralateral normal (CN) sites. The methylation levels of these 2 genes in different sites were evaluated.

Results: PAX1 and ZNF582 were both hypermethylated in OSCC compared with nontumor sites but showed different methylation patterns within the oral environment. Generally, a CL-centric methylation pattern of PAX1 where methylation levels decrease gradually from CL through AN to CN was observed, suggesting a field cancerization effect. ZNF582 methylation levels are significantly higher at lesion sites compared with normal sites, but no significant difference is observed between AN and CN. Coexistence of ZNF582 methylation in CL and AN or CN sites was also observed in some patients with OSCC. Furthermore, ZNF582 methylation was more sensitive among patients with OSCC.

Conclusions: DNA methylation detection of PAX1 and ZNF582 in the exfoliated OECs is helpful for OSCC diagnosis. Hypermethylated PAX1 and ZNF582 show different methylation patterns in the oral cavity of patients with OSCC.

Serine hydroxymethyltransferase 2 (SHMT2) is a crucial mitochondrial enzyme in 1-carbon (1C) metabolism. It catalyzes the conversion of serine to glycine, generating 1C units essential for purine and pyrimidine synthesis, thereby supporting DNA replication and repair. Abnormally high expression is associated with malignant progression and treatment tolerance in various cancers. This review systematically summarizes the functions of SHMT2 in different types of cancer, underscoring on its roles in metabolism, immune microenvironment, and key signaling pathways (PI3K/AKT/mTOR, JAK-STAT, etc.) and outlines its epigenetic regulation and posttranslational modification mechanisms. Compared with the existing research, we focused on the latest regulatory mechanisms of SHMT2 and its potential in cancer treatment, such as the development and application of small-molecule inhibitors (SHIN2 and AGF347).

Background: Computed tomography with bone scans (CT-B) has been widely used for staging metastatic hormone-sensitive prostate cancer (mHSPC), but whole-body magnetic resonance imaging (WB-MRI) is increasingly adopted. This study compares WB-MRI and CT-B in detecting metastatic sites, disease classification (CHAARTED and LATITUDE), and treatment outcomes in mHSPC.

Methods: This retrospective study included patients with mHSPC diagnosed between February 2017 and August 2023 at 2 UK NHS hospitals. Patients underwent baseline staging with either WB-MRI or CT-B. Data on demographics, disease extent, and treatment were analysed. Patients were stratified using CHAARTED and LATITUDE criteria. Survival outcomes were assessed using Kaplan-Meier and Cox regression analyses.

Results: Among 203 patients (120 WB-MRI, 83 CT-B), WB-MRI identified higher rates of bone-only disease (47% vs 22%, P < .001), high-volume (49% vs 22%, P < .001), high-risk (47% vs 18%, P < .001), and de novo metastatic disease (91% vs 65%, P < .001), but lower lymph node-only metastases (10% vs 26%, P = .003) and prior radical treatment (surgery: 2% vs 13%, P < .001; radiotherapy: 7% vs 25%, P < .001). CHAARTED (HR 4.922, 95% CI: 1.937-12.507, P < .0001) and LATITUDE (HR 4.807, 95% CI: 1.674-13.809, P = .003) classifications independently predicted overall survival, with significant volume/risk differences only observed in WB-MRI (P < .001 and P = .001, respectively).

Conclusions: Whole-body magnetic resonance imaging appears to enhance staging accuracy and risk stratification in mHSPC, potentially influencing treatment decisions. While limited by retrospective design, these findings suggest that WB-MRI may optimise management in mHSPC, warranting further prospective validation.

Background: The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, specifically the cysteine residue mutation KRAS (G12C), has garnered significant attention as a therapeutic target for solid cancer patients with KRAS mutations. Despite this interest, the efficacy and safety profiles of KRAS G12C inhibitors remain incompletely understood. In this study, we comprehensively evaluate the effectiveness and toxicity of relevant KRAS G12C inhibitors (Sotorasib, Adagrasib, Garsorasib, and Divarasib) in patients with colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), and pancreatic ductal adenocarcinomas (PDAC).

Methods: Our systematic review is guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We review the available clinical trials data on KRAS G12C inhibitors in KRAS G12C-mutated solid tumors. We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials from January 2020 until August 2023.

Results: A total of 17 eligible studies were included. KRAS G12C inhibitions with Sotorasib (41.2%) and Adagrasib (41.2%) each of them were reported in 7 studies. Divarasib was reported in 2 studies (11.8%) and Garsorasib was reported in 1 study (6.7%). Sotorasib showed a significant clinical benefit in terms of objective response rate (ORR) (7.1%-47%), progression-free survival (PFS) (4-6.8 months), and overall survival (OS) (4-24 months); it is more efficient in NSCLC patients with an OS of 2 years, PFS of 6.3 months, and an ORR of 41%. Adagrasib also showed significant clinical activity with an ORR (19%-53%), PFS (3.3-11.1 months), and OS (10.5-23.4 months), with more effectiveness in NSCLC patients with an OS of 23.4 months, PFS of 11.1 months, and an ORR of 53.3%. Adagrasib is more efficient with an ORR of 35.1%, PFS of 7.4 months, and an OS of 14 months in patients with PDAC, than Sotorasib which showed an ORR of 21%, PFS of 4 months, and an OS of 6.9 months. However, Adagrasib and Sotorasib are moderately efficient in CRC clinical trials.

Conclusion: This study confirms that patients treated with these KRAS G12C inhibitors, exclusively or combined with conventional therapies, achieve better treatment responses and modulate the progressions of these solid tumors.

Background: Detoxification enzymes of the glutathione S-transferase (GST) family are cytosolic phase II detoxification enzymes and play an important role in the normal functioning of the human antioxidant system. When the normal function of GST is disturbed or absent, there can be disturbances in cell metabolism, proliferation, and apoptosis. Deletions in the GSTM1 and GSTT1 genes have been observed in several different diseases as well as in the development of cancer. There is a need to analyze the relationship between glioma and GSTM1 and GSTT1 gene deletion to better understand the relationship between brain tumors and GST polymorphisms, which is crucial for adopting a multidisciplinary approach to prognosis and treatment of brain tumors.

Methods: In a cross-sectional clinical-laboratory study, gene deletions were examined in 34 patients with brain tumors originating from glial cells-gliomas and 88 healthy individuals. All participants were of Polish nationality and were not related.

Results: An increase in GSTM1 and GSTT1 gene deletions was observed in glioma patients compared with the control group. The greatest increase showing a marked rise of 10 times (11.8% vs 1.14%, P < .05) is in the null genotype of both genes (GSTM1-/GSTT1) [odds ratio [OR] = 0.86; 95% confidence interval [CI] = 0.09-0.802] but less in the genotype with deletion of 1 GST gene (GSTM1-/GSTT1+ and GSTM1+/GSTT1-). In addition, the findings indicated a decrease in the non-deletion genotype of both genes (GSTM1+/GSTT1+) in healthy individuals. This study showed a higher frequency of GST gene deletion in glioma patients in the studied population.

Conclusions: Based on the obtained findings, it can be said that the examination of the selected detoxification enzymes can be a useful marker in the diagnosis of glioblastoma.

Background: Emerging evidence indicates the importance of tertiary lymphoid structures (TLSs) in predicting the outcomes of nonsmall cell lung cancer (NSCLC) patients; however, their prognostic value and correlations with peripheral inflammatory prognostic indices in stage I patients have been less well studied.

Methods: Stage I NSCLC patients were recruited retrospectively; the presence and location of TLSs (peritumoral [pTLSs] and intratumoral [iTLSs]) were determined via hematoxylin and eosin (H&E)-stained slides. Peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI), were obtained and compared among these subgroups. Disease-free survival (DFS) and overall survival (OS) were tested via Kaplan-Meier analysis, and risk factors for survival were determined via a Cox proportional hazards model.

Results: A total of 24.73% and 92.73% of patients were positive for pTLSs and iTLSs, respectively. The absolute number of iTLSs was significantly greater than that of pTLSs (P < .001). Low preoperative LMR and ALI were detected only in patients with pTLSs but not in those without. Only pTLS was found to be a risk factor for both DFS and OS, and it was independently associated with OS (HR = 3.93, 95% confidence interval [CI] = 1.16-13.37; P = .028). Accordingly, patients with pTLSs had relatively poor DFS (log rank = 5.46, P = .019) and OS (log rank = 10.48, P = .001) rates.

Conclusions: Among the heterogeneous results concerning the prognostic value of pTLSs and iTLSs in stage I NSCLC, our results for the first time indicated that the presence of pTLSs may predict poor outcomes in these patients and no correlation of iTLSs with the outcomes was validated; however, additional studies with large sample size are needed in future.

Background: Cervical cancer is the second most common cancer in Bangladesh and is primarily caused by persistent high-risk human papillomavirus (HR-HPV) infection. Several risk factors, including immunological, genetic, environmental, and viral factors, may contribute to the development of cervical cancer. Moreover, a disruption in an otherwise delicate balance between immune response and cytokine production may lead to diseased states. Henceforth, this study aimed to determine and compare selected cytokines, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ), interleukin-10 (IL-10), GM-CSF, interleukin-8 (IL-8), and MCP-1 among HR-HPV-infected patients with cervical cancer, precancer individuals, and healthy participants to test the propensity of these cytokines to serve as predictive biomarkers for the detection of cervical cancer during its early stages.

Methods: A cross-sectional study was conducted on female patients visiting two referral hospitals in Bangladesh from September to November 2022. Among them, 80 women were enrolled in the study as patients with cervical cancer and precancerous lesions along with HPV DNA-negative healthy individuals. The selected cytokines in the cervical swab were estimated by flow cytometry.

Result: Cervical cancer and precancer were primarily detected in patients aged above 40 years (73.3% and 46.7% of the patients in the respective groups). Other significant risk factors, including poor educational, socioeconomic status and nutritional conditions, age of first coitus, multiparity, and tobacco and betel nut consumption, were found significant for the development of cervical cancer and precancer (P < .05). The levels of IL-6, IL-1β, IL-10, IL-8, and MCP-1 were substantially elevated in patients with cancer than in patients with precancer and healthy individuals (P < .001). Moreover, the levels of IL-6, IL-1β, IL-10, and IL-8 were also significantly increased in patients with precancer than in healthy individuals (P < .05).

Conclusions: Thus, IL-6, IL-1β, IL-10, IL-8, and MCP-1 can be used as potential biomarkers for diagnostic and prognostic purposes in HPV-induced cervical cancer and precancer.

Background: Bone metastases (BMs) are a common complication in patients with cancer, often leading to significant pain that adversely affects quality of life, necessitating effective pain management strategies. This study aims to evaluate the effectiveness of pain management in patients with BMs undergoing palliative radiotherapy and to identify determinants of pain management adequacy.

Methods: We conducted an observational analysis of 560 patients from the Palliative Radiotherapy and Inflammation Study (PRAIS) trial across several European centers, focusing on the Pain Management Index (PMI) for assessing pain management adequacy. Key predictors examined included Karnofsky Performance Status (KPS), treatment setting, primary tumor type, and site of BMs.

Results: Our findings indicate that 19.0% of patients experienced inadequate pain management (PMI < 0). Specifically, patients with KPS ⩾ 90 had a notably lower rate of adequate analgesic therapy (59.3%) compared with those with a KPS < 90 (85.0%). Among outpatients, 23.7% reported inadequate pain management, contrasted with a significantly lower inadequacy rate (3.8%) in palliative care or hospice settings. In addition, in outpatients, pain management adequacy varied with the primary tumor type, showing improved outcomes for patients with lung cancer (89.2%) versus other primary tumors (79.1%). Moreover, in non-outpatients, pain management was less effective for patients receiving radiotherapy on pelvic BMs (89.5%) compared with other sites (95.7%).

Conclusion: Although overall rates of inadequate pain management were lower than seen in previous studies, significant variability exists based on patient health status, care setting, primary tumor type, and site of BMs. These results underscore the need for personalized pain management approaches and highlight specific areas for improvement in outpatient settings and among patients with generally good health but significant pain from BMs.

Background: Research proved the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in some hematological malignancies. This study aimed to analyze the role of pretreatment NLR, LMR, PLR, RDW coefficient of variation (RDW-CV), and RDW standard deviation (RDW-SD) as prognostic markers for acute myeloid leukemia (AML).

Methods: This retrospective cohort study included 204 patients newly diagnosed with AML in the Department of Hematooncology and Bone Marrow Transplantation of the Medical University of Lublin.

Results: In the univariate models, higher RDW-CV and lower LMR predicted a poorer response to induction chemotherapy (odds ratio [OR] = 1.21, 95% confidence interval [CI95] = [1.09-2.36], P < .001; OR = 0.95, CI95 = [0.89-0.99], P = .045, respectively). In the multivariate model, age of diagnosis, ECOG (Performance Status Assessment by Eastern Cooperative Oncology Group) score, cytogenetic risk, NLR, and RDW-CV affected the odds of no response to chemotherapy significantly. The risk of progression was influenced by NLR and RDW-CV in the univariate analysis (hazard ratio [HR] = 1.20, CI95 = [1.09-1.33], P < .001; HR = 1.10, CI95 = [1.04-1.17], P = .002, respectively). In the multivariate settings, cytogenetic risk, leukocyte count, and RDW-CV affected progression free survival (PFS) significantly. Based on univariate models, the risk of death, when overall survival (OS) was taken into account, was influenced by NLR, LMR, and RDW-CV (HR = 1.05, CI95 = [1.00-1.09], P = .034; HR = 0.94, CI95 = [0.89-0.98], P = .010; HR = 1.06, CI95 = [1.01-1.10], P = .014, respectively).

Conclusions: Higher NLR, higher RDW, lower LMR, and possibly lower PLR are poor prognostic factors that may help in the risk stratification of patients with AML.

[This retracts the article DOI: 10.1177/11795549211012666.].