World Journal of Oncology最新文献

Background: Acute lymphoblastic leukemia (ALL) is relatively rare in adults with poor rates of long-term remission. Chemotherapy protocols for adults have been adapted from pediatric protocols, including asparaginase. While asparaginase has shown significant efficacy in pediatric patients, its use in adults is limited due to hepatotoxicity, pancreatitis, and thrombosis. This study seeks to review the toxicity profile in Hispanic adults at a large safety-net hospital.

Methods: We performed a chart review of patients over the age of 18 with ALL treated with asparaginase. Data were collected between the years of 2015 and 2021 and included demographics, laboratory parameters on diagnosis, treatment details, and information on complications related to treatment.

Results: A total of 14 Hispanic patients diagnosed with ALL and treated with asparaginase from January 2016 to November 2021 were included in this study. Our patient population had an average body mass index (BMI) of 34 (standard deviation (SD) 8.7), with the majority (64%) classified as obese (BMI ≥ 30). Twelve patients (86%) were Philadelphia chromosome negative. The incidence of grade 3 to 4 hyperbilirubinemia (> 3 times the upper limit of normal (ULN) for serum bilirubin) was six out of 14 patients (43%). The incidence of grade 3 to 4 transaminitis (> 5 times the ULN for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels) was 13 out of 14 patients (93%). Thrombosis occurred in six out of 14 patients (43%), with one patient experiencing disseminated intravascular coagulation (DIC).

Conclusions: Our cohort of Hispanic adults experienced transaminitis and hyperbilirubinemia at a high rate (93%). The higher incidence noted in our patients with class III obesity is in line with recent expert recommendations for dose reduction of asparaginase in patients with severe obesity. Our study suggests that our Hispanic population is at higher risk for developing hepatotoxicity after asparaginase use, though this could also be related to the high prevalence of obesity in our population. This is important for future care in selecting candidates for asparaginase therapy including those who may be at higher risk for adverse events.

Background: E26 transformation-specific variant transcription factor 7 (ETV7) is implicated in various cancers, but its role in oral squamous cell carcinoma (OSCC) remains undefined. This study explores the clinicopathological significance and molecular mechanisms of ETV7 upregulation in OSCC.

Methods: ETV7 protein expression was assessed via immunohistochemistry (IHC) in 173 OSCC and 60 non-OSCC tissues. ETV7 mRNA levels were analyzed using bulk RNA sequencing and single-cell RNA sequencing, supplemented by immune infiltration, enrichment and cell communication analysis.

Results: IHC revealed significantly higher ETV7 protein expression in OSCC than in non-OSCC tissues (P < 0.001), correlating with advanced T (r = 0.380, P < 0.001) and N stages (r = 0.592, P < 0.001). High-throughput data confirmed ETV7 mRNA upregulation (standardized mean difference (SMD) = 0.35, 95% confidence interval (CI): 0.15 - 0.56; summary receiver operating characteristic (s receiver operating characteristic) area under the curve (AUC) = 0.78, 95% CI: 0.74 - 0.81), with levels decreasing twofold post-nivolumab treatment (P < 0.001). Enrichment analysis pinpointed the immune response-regulating signaling pathway as a key mechanism, supported by elevated immune cell infiltration (e.g., CD8⁺ T cells) in high-ETV7 samples. SLC15A4 and DAB2IP emerged as potentially overexpressed ETV7 targets. Cell communication analysis showed ETV7 enhancing myeloid cell interactions via the midkine (MK) pathway.

Conclusions: ETV7 upregulation drives OSCC progression, potentially through immune microenvironment modulation, positioning it as a candidate biomarker and therapeutic target. Its association with clinical stage and immunotherapy response underscores its prognostic relevance in OSCC management.

Background: Immune checkpoint inhibitors (ICIs) can cause severe gastrointestinal immune-related adverse events (irAEs), often leading to treatment interruption and increased morbidity. Immune-mediated colitis (IMC) ranges from mild diarrhea to life-threatening colitis, sometimes requiring urgent intervention. While corticosteroids are the first-line treatment, selective immunosuppressive therapy (SIT) with either infliximab or vedolizumab is used for steroid-refractory or dependent cases. However, standardized practices are lacking, and treatment decisions are largely left to provider discretion. This study compares infliximab and vedolizumab for IMC, focusing on remission rates, recurrence, SIT dosing, and systemic steroid exposure duration.

Methods: We identified six retrospective cohort studies that compared infliximab with vedolizumab in the treatment of IMC through a systematic search of PubMed, EMBASE, Cochrane Library, Scopus, CINAHL, Google Scholar, and Web of Science in English from inception until October 2024. From the identified literature, we extracted pertinent data such as remission and recurrence of IMC. Pooled analysis and heterogeneity analysis were performed using R Studio version 4.4.1. The risk of bias was assessed using the Newcastle-Ottawa Scale.

Results: A total of six studies with 645 patients were included. In ICI-associated colitis, vedolizumab was associated with lower recurrence rates (odds ratio (OR): 0.29, 95% confidence interval (CI): 0.15 - 0.54) and shorter systemic steroid exposure (mean difference (MD): -16.88 days, 95% CI: -20.47 to -13.30) compared to infliximab. While vedolizumab showed improved remission, there was no statistically significant difference in remission rates between vedolizumab and infliximab monotherapy (OR: 3.16, 95% CI: 0.29 - 34.01). Remission was achieved with fewer doses of infliximab than vedolizumab (MD: 1.16, 95% CI: 0.09 - 2.22). The mean number of vedolizumab doses was 2.57 (raw mean score (MRAW): 2.57, 95% CI: 1.43 - 2.71), while the mean number of infliximab doses was 1.36 (MRAW: 1.36, 95% CI: 0.69 - 2.02).

Conclusions: Among patients with ICI-induced colitis, vedolizumab demonstrated superiority over infliximab by being associated with lower rates of colitis recurrence and decreased systemic steroid exposure, although it required a higher number of doses compared to infliximab.

Background: Ovarian cancer, particularly epithelial ovarian cancer (EOC), is one of the deadliest gynecological malignancies due to nonspecific early symptoms and late diagnosis. Current diagnostic tools, while useful, often do not account for regional variations in disease presentation, particularly in Asian populations. This study aimed to develop and validate a new preoperative diagnostic index tailored to the Thai population by integrating complete blood count (CBC), tumor markers, and ultrasound features.

Methods: This retrospective cohort study included patients with pathologic pelvic or adnexal masses scheduled for surgery at Vajira Hospital from April 2022 to October 2024. Clinical data, CBC, cancer antigen 125 (CA125) levels, and ultrasound findings were analyzed to develop and validate a diagnostic index (KMUTT-NMU Diagnostic Index for Ovarian Cancer (KN-DIOC)). The model's performance was compared against established indices like Risk of Malignancy Index (RMI), Risk of Ovarian Malignancy Algorithm (ROMA), and Rajavithi-Ovarian Cancer Predictive Score (R-OPS) through multivariate logistic regression, focusing on key predictors.

Results: The study comprised 195 patients divided into 151 for the development dataset and 44 for the validation dataset. The KN-DIOC showed high discriminative ability with an area under curve (AUC) of 0.866, indicating very good capability in differentiating between benign and malignant ovarian masses. The index achieved a sensitivity of 93.75% and a specificity of 78.57%, demonstrating superior performance to traditional diagnostic tools, especially in the validation dataset.

Conclusion: The novel diagnostic index (KN-DIOC), incorporating CBC, ultrasound features, and tumor markers, provides a robust tool for preoperative assessment of ovarian tumors in Thai patients. It offers significant improvements in sensitivity and specificity over existing models, suggesting its potential for broader application in similar settings. This index supports enhanced decision-making in gynecological oncology, potentially leading to better patient outcomes through timely and accurate diagnosis.

Bone is a common site of breast cancer metastasis, with the spine showing a particularly high affinity. An 83-year-old Japanese woman with Alzheimer's disease presented with a palpable mass in her left breast. A needle biopsy revealed invasive ductal carcinoma of the breast, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, with lymph node metastasis. Chest dynamic computed tomography showed no distant metastases. She was diagnosed with luminal-type, stage IIB (T2N1M0) breast cancer and underwent surgery. During induction of general anesthesia, intubation was difficult due to airway edema, necessitating bronchoscopy. The day after surgery, she reported neck pain, and radiography revealed a compression fracture of the third cervical vertebra. Magnetic resonance imaging confirmed a metastatic lesion in the third cervical vertebra. Postoperatively, she received endocrine therapy with letrozole, radiation therapy with zoledronic acid, and a cervical collar for cervical metastases. Seven months later, the osteolytic lesion calcified, and her pain improved. This case is unique because solitary cervical vertebral metastases from breast cancer, leading to compression fractures and airway edema, are rare. The case highlights the importance of considering cervical metastases in patients with breast cancer who develop airway difficulties or unexplained neck pain, particularly in the perioperative setting. Early recognition and intervention are crucial for preventing complications and optimizing patient outcomes.

Background: Invasive lobular carcinoma (ILC) accounts for approximately 10% of invasive breast carcinomas and is the most common special subtype. Most ILCs express estrogen receptors (ERs) and progesterone receptors (PRs) but typically lack ERBB2 (human epidermal growth factor receptor 2 (HER2)) overexpression. HER2-positive ILC is rare, understudied, and often linked to aggressive clinical and histopathologic features. This study aimed to examine the clinicopathologic characteristics of HER2-positive ILC to ensure proper classification and management.

Methods: A retrospective review was conducted on 48 cases, including 28 HER2-positive ILC and 20 pleomorphic invasive lobular carcinoma (p-ILC) cases without HER2 overexpression. Histological features assessed included nuclear pleomorphism, signet ring cell morphology, and apocrine features. Hormone receptor status and clinical outcomes were also analyzed.

Results: All HER2-positive ILC cases exhibited at least one pleomorphic histological feature. Hormone receptor positivity was lower in HER2-positive ILC compared to p-ILC without HER2 overexpression. However, overall survival did not significantly differ between the two groups.

Conclusion: HER2 overexpression in ILC is frequently associated with pleomorphic features. p-ILC, regardless of HER2 status, portends a worse prognosis. Identifying these features in HER2-positive ILC and classifying them as pleomorphic lobular carcinoma, a more aggressive ILC variant, is crucial for closer patient follow-up.

Background: Phosphoglycerate kinase 1 (PGK1) plays a crucial role in the glycolytic pathway and its overexpression has a negative impact on tumor development and prognosis. Resveratrol, a natural polyphenolic compound, has gained significant attention in recent years due to its anti-inflammatory, antioxidant, and anti-tumor properties. However, the mechanism by which resveratrol inhibits breast cancer growth, invasion, and metastasis through the PGK1 glycolytic pathway is still not fully understood.

Methods: We used the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas database to analyze the expression levels of glycolytic enzymes in different breast tissues and their correlation with the prognosis of breast cancer patients. The effect of resveratrol on the biological functions of breast cancer was studied through wound healing experiments and Transwell migration and invasion experiments. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot, and in vivo mouse tumorigenesis experiments were used to explore the possible molecular mechanism of resveratrol inhibiting the occurrence and development of breast cancer.

Results: Resveratrol exerted oncogenic effects both in vivo and in vitro. In our study, we provided additional evidence to support the role of resveratrol in breast cancer treatment. Specifically, we found that resveratrol effectively reduced the expression of PGK1 in BT-549 cells. This reduction is achieved by regulating an important transcription factor c-Myc. As a result, the cellular glycolytic pathway is blocked, leading to the inhibition of malignant biological behavior in breast cancer cells.

Conclusion: Our findings suggest that targeting the PGK1 glycolytic pathway could be a promising approach for resveratrol-based treatment of breast cancer.

Background: The development of targeted next-generation sequencing (NGS) technologies has contributed to precision medicine, as evidenced by the growing interest in evaluating human epidermal growth factor receptor 2 (HER2) expression status to treat unresectable/metastatic HER2-low breast cancer (BC). However, the concordance between erb-b2 receptor tyrosine kinase 2 (ERBB2) copy number alteration (CNA) and HER2 immunohistochemistry (IHC) has never been determined. The aim of this study was to evaluate the utility of targeted NGS for determining HER2 status and optimizing targeted therapies for BC.

Methods: ERBB2 CNAs were examined by targeted NGS in 41 formalin-fixed paraffin-embedded (FFPE) BC tissues. ERBB2 CNA was compared with HER2 status evaluated by IHC in tissue sections, which were identical to those subjected to targeted NGS, using the Ventana 4B5 antibody.

Results: The median fold changes (FCs) for ERBB2 CNAs in tumors with an IHC score of 3+, 2+, 1+, and 0 were 4.81, 1.49, 1.00, and 1.00, respectively. The difference in the FC for ERBB2 CNA according to HER2 status was statistically significant (P < 0.001). An FC greater than 1.0 for ERBB2 CNA was established as the cutoff value to differentiate between tumors with an IHC score of 3+, 2+, or 1+ and tumors with an IHC score of 0, on the basis of receiver operating characteristic curve analysis. The overall percent agreement, positive percent agreement, negative percent agreement, and Cohen's kappa between ERBB2 CNA and HER2 status were 68.3%, 57.7%, 86.7%, and 0.39, respectively. The numbers of patients with mutations in ERBB2, estrogen receptor 1 (ESR1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), serine/threonine kinase 1 (AKT1), and phosphatase and tensin homolog (PTEN) were 7, 3, 6, 1, and 5, respectively. Targeted NGS detected additional gene mutations and presented treatment options for seven of 22 patients (31.8%) with an FC of ERBB2 CNA = 1.00.

Conclusions: Targeted NGS has the potential in distinguishing HER2 IHC 3+, 2+, and 1+ tumors from IHC 0 in patients with BC; however, differentiating between HER2 IHC 1+ and 0 remains challenging. Additionally, targeted NGS may aid in the identification of actionable mutations, thereby contributing to the selection of optimal treatment strategies in BC management.

Background: Lung adenocarcinoma (LUAD), the predominant histological subtype of lung cancer, persists in presenting a dismally low 5-year overall survival (OS) rate, notwithstanding advancements in treatment modalities. There exists a pressing necessity for the identification of innovative biomarkers that can enhance prognostic assessments and facilitate individualized therapeutic strategies. The objective of this investigation was to clarify the involvement of genes associated with metabolic reprogramming in the progression of LUAD and to evaluate their viability as prognostic indicators.

Methods: An analysis of differential gene expression was performed utilizing The Cancer Genome Atlas (TCGA)-LUAD dataset, supplemented by a weighted gene co-expression network analysis (WGCNA). Through intersection analysis focusing on metabolic reprogramming genes (MRGs), pivotal differentially expressed metabolic reprogramming genes (hub DEMRGs) were identified. Consensus clustering categorized patients into subtypes based on these genes. Functional enrichment analysis and immune microenvironment characterization were conducted, followed by Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to construct a prognostic risk model.

Results: A total of 31 hub DEMRGs were identified. Patients were classified into two distinct subtypes (C1 and C2), with the C2 subtype exhibiting a markedly reduced OS rate. Functional enrichment revealed significant activation of nuclear division and cell cycle pathways in C2. Immune profiling demonstrated an immunosuppressive phenotype in C2, characterized by elevated M2 macrophage infiltration and reduced CD8⁺ T cells. The risk model based on five critical hub DEMRGs showed robust predictive performance (area under the curve (AUC): 0.68 - 0.71), and high-risk patients displayed unique immune cell infiltration patterns.

Conclusions: This research highlights the critical role of MRGs in LUAD prognosis and their potential for clinical application. The identified subtypes and risk model provide insights into tumor heterogeneity and immunosuppressive mechanisms, offering potential targets for individualized therapy.

Background: Educational attainment may influence colorectal cancer (CRC) risks, though the association remains inconclusive. The association might be mediated by health behaviors. This study aimed to explore the association of education on risks of CRC and to elucidate the mediatory effects of lifestyle-associated factors.

Methods: This case-control study included 174 cases and 296 healthy controls. We used a semi-structured questionnaire to collect information on participants' sociodemographic factors (age, sex, marital status, monthly income, and family history of CRC) and lifestyle-associated behaviors (smoking status, physical activity, and frequency of red meat, legumes, and vegetables intake). Body mass index (BMI) was calculated using body mass measured at first contact. Participants' education was categorized into those who completed basic education (≥ 12 years) and those who did not complete basic education (< 12 years). Logistic and multiple logistic regression analyses were employed to test the correlation between education and risk of CRC, adjusted by sociodemographic and lifestyle-associated factors. Path analysis was performed to test the mediatory effect of lifestyle-associated behaviors on the correlation.

Results: Participants with lower educational attainment had higher odds of CRC (odds ratio (OR) = 4.76, 95% confidence interval (CI) = 3.07 - 7.38), and the association remained consistent when adjusted by sociodemographic factors (adjusted OR (aOR) = 3.06, 95% CI = 1.86 - 5.03) and combined with lifestyle-associated behaviors (aOR = 2.73, 95% CI = 1.43 - 5.22). The association were consistent among men (OR = 6.14, 95% CI = 3.12 - 12.06; aOR = 4.65, 95% CI = 2.19 - 9.87; aOR = 1.05, 95% CI = 1.02 - 1.09), yet no longer significant among women when adjusted with sociodemographic and lifestyle-associated factors (OR = 3.91, 95% CI = 2.19 - 6.97; aOR = 2.02, 95% CI = 1.02 - 4.00; aOR = 1.56, 95% CI = 0.61 - 3.95). Path analysis showed that the association between educational attainment and risk of CRC was mediated by physical activity, BMI, and intake of red meat, legumes, and vegetables.

Conclusion: In our study, educational attainment was inversely correlated with the odds of CRC and might be mediated by physical activity, BMI, and intake of red meat, legumes, and vegetables. Taking other sociodemographic and lifestyle-associated factors into account, the association between lower educational attainment and higher odds of CRC was more substantial among men. These findings highlight the importance of promoting education and healthy lifestyle behaviors, particularly among men, as an essential part of targeted public health strategies in reducing burden of CRC.