Pub Date : 2023-12-01Epub Date: 2023-11-03DOI: 10.14740/wjon1737
Xu Jia Li, Meng Ge Gao, Xu Xian Chen, Yu Ming Rong, Ling Li Huang, Jin Sheng Huang
Background: Evidence from numerous observational studies and clinical trials has linked gut microbiota and metabolites to digestive tract cancer. However, the causal effect between these factors remains uncertain.
Methods: Data for this study were obtained from the MiBioGen, TwinsUK Registry, and FinnGen (version R8). Two-sample Mendelian randomization analysis with inverse variance weighting method was primarily used, and the results were validated by heterogeneity analysis, pleiotropy test, and sensitivity analysis.
Results: At P < 5 × 10-8, our analysis identified four gut microbiotas as risk factors for digestive tract cancer and six as risk factors for colorectal cancer. Conversely, one gut microbiota exhibited protection against bile duct cancer, and two showed protective effects against stomach cancer. At P < 1 × 10-5, our investigation revealed five, six, three, eight, eight, and eight gut microbiotas as risk factors for esophageal, stomach, bile duct, liver, pancreatic, and colorectal cancers, respectively. In contrast, four, two, eight, two, two, and five gut microbiotas exhibited protective effects against these cancers. Additionally, GABA, a metabolite of gut microbiota, displayed a significant protective effect against colorectal cancer.
Conclusion: In conclusion, specific gut microbiota and metabolites play roles as risk factors or protective factors for digestive tract cancer, and a causal relationship between them has been established, offering novel insights into gut microbiota-mediated cancer development.
{"title":"Genetically Predicted Causal Effects of Gut Microbiota and Gut Metabolites on Digestive Tract Cancer: A Two-Sample Mendelian Randomization Analysis.","authors":"Xu Jia Li, Meng Ge Gao, Xu Xian Chen, Yu Ming Rong, Ling Li Huang, Jin Sheng Huang","doi":"10.14740/wjon1737","DOIUrl":"https://doi.org/10.14740/wjon1737","url":null,"abstract":"<p><strong>Background: </strong>Evidence from numerous observational studies and clinical trials has linked gut microbiota and metabolites to digestive tract cancer. However, the causal effect between these factors remains uncertain.</p><p><strong>Methods: </strong>Data for this study were obtained from the MiBioGen, TwinsUK Registry, and FinnGen (version R8). Two-sample Mendelian randomization analysis with inverse variance weighting method was primarily used, and the results were validated by heterogeneity analysis, pleiotropy test, and sensitivity analysis.</p><p><strong>Results: </strong>At P < 5 × 10<sup>-8</sup>, our analysis identified four gut microbiotas as risk factors for digestive tract cancer and six as risk factors for colorectal cancer. Conversely, one gut microbiota exhibited protection against bile duct cancer, and two showed protective effects against stomach cancer. At P < 1 × 10<sup>-5</sup>, our investigation revealed five, six, three, eight, eight, and eight gut microbiotas as risk factors for esophageal, stomach, bile duct, liver, pancreatic, and colorectal cancers, respectively. In contrast, four, two, eight, two, two, and five gut microbiotas exhibited protective effects against these cancers. Additionally, <i>GABA</i>, a metabolite of gut microbiota, displayed a significant protective effect against colorectal cancer.</p><p><strong>Conclusion: </strong>In conclusion, specific gut microbiota and metabolites play roles as risk factors or protective factors for digestive tract cancer, and a causal relationship between them has been established, offering novel insights into gut microbiota-mediated cancer development.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-21DOI: 10.14740/wjon1644
Raina K Patel, Lexi Frankel, Matthew Cardeiro, Wade Hansen, Kazuaki Takabe, Omar M Rashid
Background: Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease.
Methods: The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio.
Results: The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease.
Conclusions: The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.
{"title":"The Role of Crohn Disease on Breast Cancer Incidence: A Clinical Analysis.","authors":"Raina K Patel, Lexi Frankel, Matthew Cardeiro, Wade Hansen, Kazuaki Takabe, Omar M Rashid","doi":"10.14740/wjon1644","DOIUrl":"https://doi.org/10.14740/wjon1644","url":null,"abstract":"<p><strong>Background: </strong>Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease.</p><p><strong>Methods: </strong>The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio.</p><p><strong>Results: </strong>The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10<sup>-16</sup> and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease.</p><p><strong>Conclusions: </strong>The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-21DOI: 10.14740/wjon1716
Esperanza Millan-Arreola, Diego Alberto Lozano-Jaramillo, Aida Tello De Meneses-Salazar, Oscar Omar Esquer-Cota, Luz Adriana Lavara-Miranda, Miguel Alfonso Valenzuela-Espinoza
Phyllodes tumor (PT) is considered a rare fibroepithelial tumor. Very few series have been reported in children and adolescents. Based on histopathological features, it can be classified as benign, borderline, or malignant, with the latter having a more aggressive clinical behavior. We report the case of a 10-year-old female who began with an asymptomatic mobile right breast mass. An initial fine needle biopsy (FNB) concluded fibroadenoma (FA). Months later, the mass kept growing, with the appearance of pain and nipple discharge. Benign PT was demonstrated in a new biopsy. A total mastectomy was performed. The post-surgical histopathological examination was compatible with a borderline PT. The patient is now symptom-free and with no signs of relapse. Not all breast masses in the pediatric or adolescent age bracket are FA. Attention is warranted when the clinical behavior does not follow the usual outline. PT has to be considered as a possible diagnosis and treated accordingly.
{"title":"Borderline Phyllodes Tumor in a Child.","authors":"Esperanza Millan-Arreola, Diego Alberto Lozano-Jaramillo, Aida Tello De Meneses-Salazar, Oscar Omar Esquer-Cota, Luz Adriana Lavara-Miranda, Miguel Alfonso Valenzuela-Espinoza","doi":"10.14740/wjon1716","DOIUrl":"https://doi.org/10.14740/wjon1716","url":null,"abstract":"<p><p>Phyllodes tumor (PT) is considered a rare fibroepithelial tumor. Very few series have been reported in children and adolescents. Based on histopathological features, it can be classified as benign, borderline, or malignant, with the latter having a more aggressive clinical behavior. We report the case of a 10-year-old female who began with an asymptomatic mobile right breast mass. An initial fine needle biopsy (FNB) concluded fibroadenoma (FA). Months later, the mass kept growing, with the appearance of pain and nipple discharge. Benign PT was demonstrated in a new biopsy. A total mastectomy was performed. The post-surgical histopathological examination was compatible with a borderline PT. The patient is now symptom-free and with no signs of relapse. Not all breast masses in the pediatric or adolescent age bracket are FA. Attention is warranted when the clinical behavior does not follow the usual outline. PT has to be considered as a possible diagnosis and treated accordingly.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-18DOI: 10.14740/wjon1605
Matthew G K Benesch, Erek D Nelson, Shalana B L O'Brien
Signet ring cell adenocarcinomas (SRCCs) are a rare and aggressive histological subtype of adenocarcinomas typically with poor prognosis usually secondary to late stage at detection. In the small bowel, they constitute only 1% of all malignancies. In the last decade, there have been multiple case reports and small case series that have identified SRCCs, typically in the ileum, in patients with Crohn's disease. Crohn's disease is a transmural inflammatory condition that normally manifests in the distal ileum and colon, and is known to temporally increase the risk of malignancy. Given the profound rarity of SRCCs, establishing an association between Crohn's disease and SRCC is challenging. In this study, we performed a systematic review of case reports and small case series describing small bowel SRCCs in Crohn's disease patients. Most cases were found in the distal/terminal ileum, at a mean age of 59 years old. Virtually all tumors were locally advanced (pathological T stage 3 and 4), typically with at least N1 nodal disease. Two case studies (one is a case-control study and the other a cohort design) demonstrated that small bowel SRCC, as opposed to conventional adenocarcinoma, was significantly correlated to a history of Crohn's disease (35% vs. 0%, 73.5% vs. 28.5%), with a propensity to arise in the ileum (95% vs. 30%, 66.7% vs. 42.1%), and at earlier mean age (43 vs. 68 years, 53.7 vs. 61.7 years). We additionally used the Surveillance, Epidemiology, and End Results (SEER) database for insights into the clinicoepidemiological characteristics of ileum SRCCs. SRCCs composed 28.1% of all ileal SRCCs, compared to 11.0% for the adenocarcinomas, with a younger age at diagnosis (60.7 vs. 64.6 years), more distant disease at presentation (41.3% vs. 26.4%), and shorter overall median survival time (20 vs. 39 months). In summary, while there is limited direct evidence to support an association between small bowel SRCC and Crohn's disease, the phenomenon has been increasingly documented in the literature in the last decade. Clinicians treating Crohn's disease patients should consider this in their differential diagnosis, particularly when managing disease complications, as early detection and surgical intervention offer the best prognosis.
{"title":"Malignant Transformation of Long-Standing Ileal Crohn's Disease Likely Favors Signet Ring Cell Adenocarcinoma Histology.","authors":"Matthew G K Benesch, Erek D Nelson, Shalana B L O'Brien","doi":"10.14740/wjon1605","DOIUrl":"10.14740/wjon1605","url":null,"abstract":"<p><p>Signet ring cell adenocarcinomas (SRCCs) are a rare and aggressive histological subtype of adenocarcinomas typically with poor prognosis usually secondary to late stage at detection. In the small bowel, they constitute only 1% of all malignancies. In the last decade, there have been multiple case reports and small case series that have identified SRCCs, typically in the ileum, in patients with Crohn's disease. Crohn's disease is a transmural inflammatory condition that normally manifests in the distal ileum and colon, and is known to temporally increase the risk of malignancy. Given the profound rarity of SRCCs, establishing an association between Crohn's disease and SRCC is challenging. In this study, we performed a systematic review of case reports and small case series describing small bowel SRCCs in Crohn's disease patients. Most cases were found in the distal/terminal ileum, at a mean age of 59 years old. Virtually all tumors were locally advanced (pathological T stage 3 and 4), typically with at least N1 nodal disease. Two case studies (one is a case-control study and the other a cohort design) demonstrated that small bowel SRCC, as opposed to conventional adenocarcinoma, was significantly correlated to a history of Crohn's disease (35% vs. 0%, 73.5% vs. 28.5%), with a propensity to arise in the ileum (95% vs. 30%, 66.7% vs. 42.1%), and at earlier mean age (43 vs. 68 years, 53.7 vs. 61.7 years). We additionally used the Surveillance, Epidemiology, and End Results (SEER) database for insights into the clinicoepidemiological characteristics of ileum SRCCs. SRCCs composed 28.1% of all ileal SRCCs, compared to 11.0% for the adenocarcinomas, with a younger age at diagnosis (60.7 vs. 64.6 years), more distant disease at presentation (41.3% vs. 26.4%), and shorter overall median survival time (20 vs. 39 months). In summary, while there is limited direct evidence to support an association between small bowel SRCC and Crohn's disease, the phenomenon has been increasingly documented in the literature in the last decade. Clinicians treating Crohn's disease patients should consider this in their differential diagnosis, particularly when managing disease complications, as early detection and surgical intervention offer the best prognosis.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-10-21DOI: 10.14740/wjon1685
Syah Mirsya Warli, Adrian Joshua Velaro, Naufal Nandita Firsty, Zaimah Zulkarnaini Tala
Background: The emergence of olaparib, a poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor to treat metastatic castration-resistant prostate cancer (mCRPC), created a measurable clinical question on whether the agent positively influences the treatment outcomes and acceptable safety factors. The objective was to elaborate on the efficacy and safety of olaparib-added regimens in treating mCRPC patients as compared to the established guideline.
Methods: The literature search was performed on several scientific databases, e.g., PubMed, Cochrane, and ScienceDirect, by applying the Boolean Term method. Statistical and risk of bias (RoB) analyses were calculated through RevMan 5.4.1. to investigate our outcomes, i.e., progression-free survival (PFS) and overall survival (OS) with the reported adverse effects (AEs). These outcomes were presented in hazard ratio (HR) and risk ratio (RR).
Results: Three trials consisting of 1,325 individuals with comparable baseline characteristics were investigated. The meta-analysis showed that introducing olaparib into the regimens significantly improved the PFS (HR 0.59 (0.48 - 0.73); P < 0.05), which disclosed even better outcomes among mutated homologous recombinant repair (HRR) and ataxia-telangiectasia mutated (ATM) gene (HR 0.43 (0.30 - 0.62); P < 0.05) in 95% confidence interval (CI). Furthermore, similar outcomes were observed in OS analysis (HR 0.81 (0.67 - 0.99); P < 0.05), despite olaparib group disclosed higher AEs rate with insignificant difference in mortality rate.
Conclusion: The efficacy and safety of olaparib-added regimens in mCRPC patients need to be explored more extensively in trials because they are beneficial, particularly among HRR-mutated individuals.
{"title":"Addition of Olaparib to the New Hormonal Agent Regimen for Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.","authors":"Syah Mirsya Warli, Adrian Joshua Velaro, Naufal Nandita Firsty, Zaimah Zulkarnaini Tala","doi":"10.14740/wjon1685","DOIUrl":"https://doi.org/10.14740/wjon1685","url":null,"abstract":"<p><strong>Background: </strong>The emergence of olaparib, a poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor to treat metastatic castration-resistant prostate cancer (mCRPC), created a measurable clinical question on whether the agent positively influences the treatment outcomes and acceptable safety factors. The objective was to elaborate on the efficacy and safety of olaparib-added regimens in treating mCRPC patients as compared to the established guideline.</p><p><strong>Methods: </strong>The literature search was performed on several scientific databases, e.g., PubMed, Cochrane, and ScienceDirect, by applying the Boolean Term method. Statistical and risk of bias (RoB) analyses were calculated through RevMan 5.4.1. to investigate our outcomes, i.e., progression-free survival (PFS) and overall survival (OS) with the reported adverse effects (AEs). These outcomes were presented in hazard ratio (HR) and risk ratio (RR).</p><p><strong>Results: </strong>Three trials consisting of 1,325 individuals with comparable baseline characteristics were investigated. The meta-analysis showed that introducing olaparib into the regimens significantly improved the PFS (HR 0.59 (0.48 - 0.73); P < 0.05), which disclosed even better outcomes among mutated homologous recombinant repair (HRR) and ataxia-telangiectasia mutated (ATM) gene (HR 0.43 (0.30 - 0.62); P < 0.05) in 95% confidence interval (CI). Furthermore, similar outcomes were observed in OS analysis (HR 0.81 (0.67 - 0.99); P < 0.05), despite olaparib group disclosed higher AEs rate with insignificant difference in mortality rate.</p><p><strong>Conclusion: </strong>The efficacy and safety of olaparib-added regimens in mCRPC patients need to be explored more extensively in trials because they are beneficial, particularly among <i>HRR</i>-mutated individuals.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-18DOI: 10.14740/wjon1715
Natasha T Sobol, Luisina M Solerno, Candela Llavona, Daniel F Alonso, Juan Garona
Background: Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC, 5-fluorouracil (5-FU) clinical use has severe limitations, such as high toxicity, low selectivity and drug resistance. [V4Q5]dDAVP (1-deamino-4-valine-5-glutamine-8-D-arginine vasopressin) is a peptide vasopressin analog and a selective agonist of the arginine vasopressin type 2 membrane receptor (AVPR2), expressed in microvascular and tumor tissue. This synthetic compound has well-proven antitumor and antimetastatic activity in different tumor types, including metastatic CRC. The objective of this work was to assess the potential combinational benefits in preclinical CRC models after [V4Q5]dDAVP addition to 5-FU.
Methods: Effects on cellular viability, cell cycle progression, apoptosis and molecular mechanisms associated to [V4Q5]dDAVP treatment in combination with 5-FU were evaluated in murine CT-26 and human COLO-205 cell lines. In vivo, impact of dual therapy was explored on CRC tumor growth and metastatic spread.
Results: In CRC cells, [V4Q5]dDAVP (1 µM) addition to sub-IC50 5-FU concentrations resulted in the enhancement of cytostatic effects induced by chemotherapy. Reduction of cell viability after combined treatment was associated with cell cycle arrest in the G0/G1 phase, induction of apoptosis and increased gene expression of the cyclin-dependent kinase inhibitor p21 (CDKN1A) and the tumor suppressor p53 (TP53) in malignant cells, as assessed by flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. In vivo, intravenous administration of [V4Q5]dDAVP (0.3 µg/kg) in combination with safe low doses of 5-FU (50 or 80 mg/kg for CT-26 or COLO-205 tumor models, respectively) effectively abrogated CRC growth, reducing aggressiveness of primary lesions and increasing survival of tumor-bearing mice. In addition, concomitant administration of [V4Q5]dDAVP and 5-FU inhibited pulmonary metastasis formation by CT-26 cells in immunocompetent mice, especially reducing macrometastatic disease.
Conclusions: [V4Q5]dDAVP seems to enhance the efficacy of 5-FU-based chemotherapy in CRC by modulating tumor progression, as well as metastatic dissemination, suggesting its potential role as a safe and cost-effective co-adjuvant agent for the management of advanced CRC.
背景:结直肠癌(CRC)是世界范围内癌症相关死亡的主要原因。尽管5-氟尿嘧啶(5-FU)是晚期结直肠癌全身化疗的重要组成部分,但其临床应用存在严重的局限性,如高毒性、低选择性和耐药。[V4Q5]dDAVP(1-脱氨基-4-缬氨酸-5-谷氨酰胺-8- d -精氨酸加压素)是一种肽加压素类似物和精氨酸加压素2型膜受体(AVPR2)的选择性激动剂,在微血管和肿瘤组织中表达。该合成化合物在包括转移性结直肠癌在内的不同肿瘤类型中具有良好的抗肿瘤和抗转移活性。本研究的目的是评估[V4Q5]dDAVP加5-FU后在临床前CRC模型中的潜在联合获益。方法:研究[V4Q5]dDAVP联合5-FU对小鼠CT-26和人COLO-205细胞系细胞活力、细胞周期进程、凋亡的影响及其分子机制。在体内,研究了双重治疗对结直肠癌肿瘤生长和转移扩散的影响。结果:在结直肠癌细胞中,[V4Q5]dDAVP(1µM)加入亚ic50浓度的5-FU可增强化疗诱导的细胞抑制作用。通过流式细胞术、末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸(dUTP) nick末端标记(TUNEL)和定量逆转录聚合酶链反应(qRT-PCR)评估,联合治疗后细胞活力降低与恶性细胞周期阻滞在G0/G1期、诱导细胞凋亡和细胞周期蛋白依赖性激酶抑制剂p21 (CDKN1A)和肿瘤抑制因子p53 (TP53)的基因表达增加有关。分别。在体内,静脉给药[V4Q5]dDAVP(0.3µg/kg)联合安全的低剂量5-FU (CT-26或COLO-205肿瘤模型分别为50或80 mg/kg)有效地抑制了CRC的生长,降低了原发病变的侵袭性,提高了荷瘤小鼠的存活率。此外,同时给予[V4Q5]dDAVP和5-FU可抑制免疫活性小鼠CT-26细胞的肺转移形成,特别是减少大转移性疾病。结论:dDAVP似乎通过调节肿瘤进展和转移性传播来增强5- fu化疗在结直肠癌中的疗效,提示其作为一种安全、经济的晚期结直肠癌辅助佐剂的潜在作用。
{"title":"Vasopressin Analog [V<sup>4</sup>Q<sup>5</sup>]dDAVP Exerts Cooperative Anticancer Effects in Combination With Low-Dose 5-Fluorouracil on Aggressive Colorectal Cancer Models.","authors":"Natasha T Sobol, Luisina M Solerno, Candela Llavona, Daniel F Alonso, Juan Garona","doi":"10.14740/wjon1715","DOIUrl":"https://doi.org/10.14740/wjon1715","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Despite being an essential component of systemic chemotherapy for advanced CRC, 5-fluorouracil (5-FU) clinical use has severe limitations, such as high toxicity, low selectivity and drug resistance. [V<sup>4</sup>Q<sup>5</sup>]dDAVP (1-deamino-4-valine-5-glutamine-8-D-arginine vasopressin) is a peptide vasopressin analog and a selective agonist of the arginine vasopressin type 2 membrane receptor (AVPR2), expressed in microvascular and tumor tissue. This synthetic compound has well-proven antitumor and antimetastatic activity in different tumor types, including metastatic CRC. The objective of this work was to assess the potential combinational benefits in preclinical CRC models after [V<sup>4</sup>Q<sup>5</sup>]dDAVP addition to 5-FU.</p><p><strong>Methods: </strong>Effects on cellular viability, cell cycle progression, apoptosis and molecular mechanisms associated to [V<sup>4</sup>Q<sup>5</sup>]dDAVP treatment in combination with 5-FU were evaluated in murine CT-26 and human COLO-205 cell lines. <i>In vivo</i>, impact of dual therapy was explored on CRC tumor growth and metastatic spread.</p><p><strong>Results: </strong>In CRC cells, [V<sup>4</sup>Q<sup>5</sup>]dDAVP (1 µM) addition to sub-IC<sub>50</sub> 5-FU concentrations resulted in the enhancement of cytostatic effects induced by chemotherapy. Reduction of cell viability after combined treatment was associated with cell cycle arrest in the G<sub>0</sub>/G<sub>1</sub> phase, induction of apoptosis and increased gene expression of the cyclin-dependent kinase inhibitor p21 (CDKN1A) and the tumor suppressor p53 (TP53) in malignant cells, as assessed by flow cytometry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. <i>In vivo</i>, intravenous administration of [V<sup>4</sup>Q<sup>5</sup>]dDAVP (0.3 µg/kg) in combination with safe low doses of 5-FU (50 or 80 mg/kg for CT-26 or COLO-205 tumor models, respectively) effectively abrogated CRC growth, reducing aggressiveness of primary lesions and increasing survival of tumor-bearing mice. In addition, concomitant administration of [V<sup>4</sup>Q<sup>5</sup>]dDAVP and 5-FU inhibited pulmonary metastasis formation by CT-26 cells in immunocompetent mice, especially reducing macrometastatic disease.</p><p><strong>Conclusions: </strong>[V<sup>4</sup>Q<sup>5</sup>]dDAVP seems to enhance the efficacy of 5-FU-based chemotherapy in CRC by modulating tumor progression, as well as metastatic dissemination, suggesting its potential role as a safe and cost-effective co-adjuvant agent for the management of advanced CRC.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR).
Methods: We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals.
Results: The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group.
Conclusions: AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.
背景:大汗腺癌(AC)是一种罕见的乳腺癌类型,在日本的所有乳腺癌中患病率仅为1%,其临床病理特征尚不清楚。本研究的目的是评估AC的特征和预后,与雄激素受体(AR)的存在或缺失有关。方法:我们在日本进行了一项回顾性多中心病例对照研究(横滨临床肿瘤组(YCOG): YCOG1701研究)。在2000年至2017年期间,共有53名患者在ycog附属医院被诊断为AC。结果:患者中位年龄67(43 ~ 94)岁,中位观察时间6.1年。53例中,纯AC (TN-PAC)三阴性24例;ar阳性),而29例有其他类型的AC (other-AC;雌激素受体阳性和/或人表皮生长因子受体2阳性或ar阴性)。与其他ac组相比,TN-PAC组肿瘤体积更小(1.4 cm vs 2.1 cm, P = 0.024),淋巴结转移发生率更低(12.5% vs 37.9%, P = 0.036)。两组患者接受围手术期辅助化疗的人数无显著差异(TN-PAC/other-AC = 50.0%/55.2%, P = 0.525);然而,与其他ac组的5例复发相比,TN-PAC组没有复发。结论:ar阳性AC患者无需辅助化疗预后良好,即使是TN亚型。预计将进行一项临床试验,探索治疗降级的可能性。
{"title":"Clinicopathological Characteristics and Prognosis of Triple-Negative Apocrine Carcinoma: A Case-Control Study.","authors":"Chiho Suzuki, Akimitsu Yamada, Kei Kawashima, Mahato Sasamoto, Yoshie Fujiwara, Shoko Adachi, Masanori Oshi, Tomoko Wada, Shinya Yamamoto, Kazuhiro Shimada, Ikuko Ota, Kazutaka Narui, Sadatoshi Sugae, Daisuke Shimizu, Mikiko Tanabe, Takashi Chishima, Yasushi Ichikawa, Takashi Ishikawa, Itaru Endo","doi":"10.14740/wjon1694","DOIUrl":"https://doi.org/10.14740/wjon1694","url":null,"abstract":"<p><strong>Background: </strong>With a prevalence of only 1% among all breast cancers in Japan, apocrine carcinoma (AC) is a rare type of breast cancer, and its clinicopathological characteristics remain unclear. The aim of this study was to evaluate the characteristics and prognosis of AC, in relation to the presence or absence of androgen receptor (AR).</p><p><strong>Methods: </strong>We conducted a retrospective multi-center case-control study (Yokohama Clinical Oncology Group (YCOG): YCOG1701 study) in Japan. A total of 53 patients were registered who were diagnosed with AC between 2000 and 2017 in YCOG-affiliated hospitals.</p><p><strong>Results: </strong>The median age of the patients was 67 (43 - 94) years, and the median observation time was 6.1 years. Among the 53 cases, 24 had triple-negative pure AC (TN-PAC; AR-positive), whereas 29 had other types of AC (other-AC; estrogen receptor-positive and/or human epidermal growth factor receptor 2-positive or AR-negative). Tumor size was smaller (1.4 vs. 2.1 cm, P = 0.024) and metastasis occurred in fewer nodes (12.5% vs. 37.9%, P = 0.036) in the TN-PAC group than in the other-AC group. The number of patients who were administered perioperative adjuvant chemotherapy did not significantly differ between the two groups (TN-PAC/other-AC = 50.0%/55.2%, P = 0.525); however, there was no recurrence in the TN-PAC group, compared to five cases with relapse in the other-AC group.</p><p><strong>Conclusions: </strong>AR-positive AC patients showed a favorable prognosis without adjuvant chemotherapy, even with the TN subtype. A clinical trial exploring the possibility of treatment de-escalation is anticipated.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-03DOI: 10.14740/wjon1553
Xu Dong Zhu, Jia Hui Yu, Fu Lu Ai, Yue Wang, Wu Lv, Gui Lin Yu, Xian Kui Cao, Jie Lin
Background: Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.
Methods: We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.
Results: The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.
Conclusions: The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.
{"title":"Construction and Validation of a Novel Nomogram for Predicting the Risk of Metastasis in a Luminal B Type Invasive Ductal Carcinoma Population.","authors":"Xu Dong Zhu, Jia Hui Yu, Fu Lu Ai, Yue Wang, Wu Lv, Gui Lin Yu, Xian Kui Cao, Jie Lin","doi":"10.14740/wjon1553","DOIUrl":"https://doi.org/10.14740/wjon1553","url":null,"abstract":"<p><strong>Background: </strong>Postoperative distant metastasis is the main cause of death in breast cancer patients. We aimed to construct a nomogram to predict the risk of metastasis of luminal B type invasive ductal carcinoma.</p><p><strong>Methods: </strong>We applied the data of 364 luminal B type breast cancer patients between 2008 and 2013. Patients were categorized into modeling group and validation group randomly (1:1). The breast cancer metastasis nomogram was developed from the logistic regression model using clinicopathological variables. The area under the receiver-operating characteristic curve (AUC) was calculated in modeling group and validation group to evaluate the predictive accuracy of the nomogram.</p><p><strong>Results: </strong>The multivariate logistic regression analysis showed that tumor size, No. of the positive level 1 axillary lymph nodes, human epidermal growth factor receptor 2 (HER2) status and Ki67 index were the independent predictors of the breast cancer metastasis. The AUC values of the modeling group and the validation group were 0.855 and 0.818, respectively. The nomogram had a well-fitted calibration curve. The positive and negative predictive values were 49.3% and 92.7% in the modeling group, and 47.9% and 91.0% in the validation group. Patients who had a score of 60 or more were thought to have a high risk of breast cancer metastasis.</p><p><strong>Conclusions: </strong>The nomogram has a great predictive accuracy of predicting the risk of breast cancer metastasis. If patients had a score of 60 or more, necessary measures, like more standard treatment methods and higher treatment adherence of patients, are needed to take to lower the risk of metastasis and improve the prognosis.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-18DOI: 10.14740/wjon1718
Ze Nan Liu, Zi Ang Li, Ji De He, Jia Long Wu, Lei Qiu, Zhen Kun Zhao, Min Lu, Hai Bi, Jian Lu
Background: The aim of the study was to investigate the predictive value of the nutritional risk index (NRI) for extracapsular extension (ECE) and seminal vesicle invasion (SVI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), and further develop and validate predictive nomograms for ECE and SVI based on the NRI.
Methods: We retrospectively analyzed 734 PCa patients who underwent RP between 2010 and 2020 in the Department of Urology at Peking University Third Hospital. The enrolled patients were randomly divided into a primary cohort (n = 489) and a validation cohort (n = 245) in a 2:1 manner. The baseline NRI of patients was calculated using serum albumin level and body mass index, and a malnutrition status was defined as NRI ≤ 98. Univariate and multivariate logistic regression analyses were conducted to identify predictors for ECE and SVI. Nomograms for predicting ECE and SVI were established based on the results of the multivariate logistic regression analysis. The performance of the nomograms was estimated using Harrell's concordance index (C-index), the area under curve (AUC) of receiver operating characteristic (ROC) curves and the calibration curves.
Results: In the primary cohort, 70 (14.3%) patients with NRI ≤ 98 were classified as malnutrition, while the remaining 419 (85.7%) patients with NRI > 98 were considered to have normal nutrition. The nomograms for predicting ECE and SVI shared common factors including NRI, percentage of positive biopsy cores (PPC) and biopsy Gleason score, while prostate-specific antigen (PSA) levels and PSA density (PSAD) were only incorporated in ECE nomogram. The C-indexes of the nomograms for predicting ECE and SVI were 0.785 (95% confidence interval (CI): 0.745 - 0.826) and 0.852 (95% CI: 0.806 - 0.898), respectively. The calibration curves demonstrated excellent agreement between the predictions by the nomograms and the actual observations. The results remained reproducible when the nomograms were applied to the validation cohort.
Conclusions: The NRI is significantly associated with ECE and SVI in PCa patients. The nomogram established based on the NRI in our study can provide individualized risk estimation for ECE and SVI in PCa patients, and may be valuable for clinicians in making well-informed decisions regarding treatment strategies and patient management.
{"title":"Development and Validation of Nomograms Based on Nutritional Risk Index for Predicting Extracapsular Extension and Seminal Vesicle Invasion in Patients Undergoing Radical Prostatectomy.","authors":"Ze Nan Liu, Zi Ang Li, Ji De He, Jia Long Wu, Lei Qiu, Zhen Kun Zhao, Min Lu, Hai Bi, Jian Lu","doi":"10.14740/wjon1718","DOIUrl":"https://doi.org/10.14740/wjon1718","url":null,"abstract":"<p><strong>Background: </strong>The aim of the study was to investigate the predictive value of the nutritional risk index (NRI) for extracapsular extension (ECE) and seminal vesicle invasion (SVI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), and further develop and validate predictive nomograms for ECE and SVI based on the NRI.</p><p><strong>Methods: </strong>We retrospectively analyzed 734 PCa patients who underwent RP between 2010 and 2020 in the Department of Urology at Peking University Third Hospital. The enrolled patients were randomly divided into a primary cohort (n = 489) and a validation cohort (n = 245) in a 2:1 manner. The baseline NRI of patients was calculated using serum albumin level and body mass index, and a malnutrition status was defined as NRI ≤ 98. Univariate and multivariate logistic regression analyses were conducted to identify predictors for ECE and SVI. Nomograms for predicting ECE and SVI were established based on the results of the multivariate logistic regression analysis. The performance of the nomograms was estimated using Harrell's concordance index (C-index), the area under curve (AUC) of receiver operating characteristic (ROC) curves and the calibration curves.</p><p><strong>Results: </strong>In the primary cohort, 70 (14.3%) patients with NRI ≤ 98 were classified as malnutrition, while the remaining 419 (85.7%) patients with NRI > 98 were considered to have normal nutrition. The nomograms for predicting ECE and SVI shared common factors including NRI, percentage of positive biopsy cores (PPC) and biopsy Gleason score, while prostate-specific antigen (PSA) levels and PSA density (PSAD) were only incorporated in ECE nomogram. The C-indexes of the nomograms for predicting ECE and SVI were 0.785 (95% confidence interval (CI): 0.745 - 0.826) and 0.852 (95% CI: 0.806 - 0.898), respectively. The calibration curves demonstrated excellent agreement between the predictions by the nomograms and the actual observations. The results remained reproducible when the nomograms were applied to the validation cohort.</p><p><strong>Conclusions: </strong>The NRI is significantly associated with ECE and SVI in PCa patients. The nomogram established based on the NRI in our study can provide individualized risk estimation for ECE and SVI in PCa patients, and may be valuable for clinicians in making well-informed decisions regarding treatment strategies and patient management.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-11-18DOI: 10.14740/wjon1661
Renzo Martin Chapilliquen Ramirez, Mariana Teresa de Jesus Corbacho Pachas, Richard Junior Zapata Dongo
Background: Core binding factor acute myeloid leukemia (CBF-AML) comprises t(8;21) and inv(16) and usually has a favorable prognosis. However, a wide spectrum of secondary genetic aberrations has been shown to be associated with worse outcomes with respect to overall survival (OS) and relapse. We aimed to identify secondary molecular and chromosomal aberrations within each group of CBF-AML, i.e., t(8;21) and inv(16), and to evaluate their prognosis with OS.
Methods: Using the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, we analyzed 193 cases of CBF-AML reported between 2011 and 2021. We conducted a survival analysis to determine the 5-year OS, and we conducted univariate and multivariate Cox regression to identify independent genetic factors related to OS.
Results: Among the 193 cases with CBF-AML, structural and numerical chromosome rearrangements were 25.9% and 40.9%, respectively, and secondary genetic mutations were 54.9%. The 5-year OS for the presence of del(7) and trisomy 22 was significantly worse. NRAS mutations had a worse 5-year OS in the t(8;21) group in the univariate analysis but showed no significant difference in the multivariate analysis.
Conclusions: CBF-AML has heterogeneous cytogenetic characteristics but no difference in the 5-year OS between the inv(16) and t(8;21) groups. Finally, the presence of del(7), trisomy 22 and NRAS mutations showed a potential prognostic impact in CBF-AML patients. Secondary genetic findings may need to be identified to determine its association to a worse prognosis, and in the future develop better targeted therapies in patients with CBF-AML.
{"title":"Prevalence and Prognosis of Secondary Genetic Aberrations Among Patients With Core Binding Factor Acute Myeloid Leukemia: A Mitelman Database Analysis.","authors":"Renzo Martin Chapilliquen Ramirez, Mariana Teresa de Jesus Corbacho Pachas, Richard Junior Zapata Dongo","doi":"10.14740/wjon1661","DOIUrl":"https://doi.org/10.14740/wjon1661","url":null,"abstract":"<p><strong>Background: </strong>Core binding factor acute myeloid leukemia (CBF-AML) comprises t(8;21) and inv(16) and usually has a favorable prognosis. However, a wide spectrum of secondary genetic aberrations has been shown to be associated with worse outcomes with respect to overall survival (OS) and relapse. We aimed to identify secondary molecular and chromosomal aberrations within each group of CBF-AML, i.e., t(8;21) and inv(16), and to evaluate their prognosis with OS.</p><p><strong>Methods: </strong>Using the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, we analyzed 193 cases of CBF-AML reported between 2011 and 2021. We conducted a survival analysis to determine the 5-year OS, and we conducted univariate and multivariate Cox regression to identify independent genetic factors related to OS.</p><p><strong>Results: </strong>Among the 193 cases with CBF-AML, structural and numerical chromosome rearrangements were 25.9% and 40.9%, respectively, and secondary genetic mutations were 54.9%. The 5-year OS for the presence of del(7) and trisomy 22 was significantly worse. <i>NRAS</i> mutations had a worse 5-year OS in the t(8;21) group in the univariate analysis but showed no significant difference in the multivariate analysis.</p><p><strong>Conclusions: </strong>CBF-AML has heterogeneous cytogenetic characteristics but no difference in the 5-year OS between the inv(16) and t(8;21) groups. Finally, the presence of del(7), trisomy 22 and <i>NRAS</i> mutations showed a potential prognostic impact in CBF-AML patients. Secondary genetic findings may need to be identified to determine its association to a worse prognosis, and in the future develop better targeted therapies in patients with CBF-AML.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}