OncologyPub Date : 2025-01-01Epub Date: 2024-08-12DOI: 10.1159/000540863
Luděk Záveský, Eva Jandáková, Vit Weinberger, Luboš Minář, Milada Kohoutová, Adela Tefr Faridová, Ondřej Slanař
{"title":"The Overexpressed MicroRNAs miRs-182, 155, 493, 454, and U6 snRNA and Underexpressed let-7c, miR-328, and miR-451a as Potential Biomarkers in Invasive Breast Cancer and Their Clinicopathological Significance.","authors":"Luděk Záveský, Eva Jandáková, Vit Weinberger, Luboš Minář, Milada Kohoutová, Adela Tefr Faridová, Ondřej Slanař","doi":"10.1159/000540863","DOIUrl":"10.1159/000540863","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers.</p><p><strong>Methods: </strong>This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data.</p><p><strong>Results: </strong>Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations.</p><p><strong>Conclusion: </strong>We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.</p><p><strong>Introduction: </strong>Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers.</p><p><strong>Methods: </strong>This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data.</p><p><strong>Results: </strong>Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated wi","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"112-127"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-07-29DOI: 10.1159/000540637
Miho Takemura, Kenji Ikemura, Masahiro Okuda
{"title":"Effect of Hydration with Bicarbonate Ringer's Solution on Cisplatin-Induced Acute Kidney Injury in Patients with Esophageal Cancer: A Retrospective Cohort Study.","authors":"Miho Takemura, Kenji Ikemura, Masahiro Okuda","doi":"10.1159/000540637","DOIUrl":"10.1159/000540637","url":null,"abstract":"<p><strong>Introduction: </strong>Cisplatin (CDDP) often causes acute kidney injury (AKI), and magnesium supplementation has been suggested to be important in preventing CDDP-induced AKI. Sodium bicarbonate Ringer's solution (BRS) is a crystalloid solution composed of various electrolytes, including Mg2+, and can be generally used to supplement missing extracellular fluid and correct metabolic acidosis; however, the clinical outcomes of hydration with BRS for CDDP-induced AKI remain unclear. In this study, we retrospectively compared the effects of BRS and normal saline for hydration in patients undergoing CDDP treatment.</p><p><strong>Methods: </strong>We analyzed the incidence rate of AKI (grade ≥ 1), the severity of AKI, the serum magnesium level, and the incidence rate of grade ≥ 3 hematological toxicities (leukopenia, neutropenia, anemia, or thrombocytopenia) following CDDP and fluorouracil (5-FU) administration in 131 in-patients who received CDDP and 5-FU for the first time to treat esophageal cancer.</p><p><strong>Results: </strong>Fifty-six patients (43%) received saline alone, while 75 patients (57%) received BRS for hydration. The incidence rate of AKI (grade ≥ 1) was significantly lower in the BRS group (11%) than that in the saline group (39%, p < 0.001). Moreover, severe AKI (grade ≥ 2) was significantly less common in the BRS group than in the saline group. Although the serum magnesium levels before CDDP administration were not significantly different between the two groups (p = 0.939), the serum magnesium levels on days 2-3 after CDDP administration in the BRS group were significantly higher than those in the saline group (p < 0.001). In contrast, there were no significant differences in the incidence rates of hematological toxicity between the two groups. Multivariate analysis revealed that BRS use was an independent factor that significantly contributed to AKI prevention (odds ratio = 0.061, p < 0.001).</p><p><strong>Conclusion: </strong>Hydration with BRS could prevent CDDP-induced AKI in patients with esophageal cancer.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"22-29"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-08-19DOI: 10.1159/000540936
Yu Liang, Yongmin Li, Rui Guo, Yan Zhao, Huanshuo Miao, Hong Chang, Yue Chen
{"title":"Identification and Initial Validation of Neuroendocrine Differentiation as a Novel Prognostic Factor in Stage II Colorectal Cancer Patients.","authors":"Yu Liang, Yongmin Li, Rui Guo, Yan Zhao, Huanshuo Miao, Hong Chang, Yue Chen","doi":"10.1159/000540936","DOIUrl":"10.1159/000540936","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroendocrine differentiation is often found in colorectal cancer, but its impact on prognosis remains controversial. This study explored the association between neuroendocrine differentiation and prognosis in stage II/III colorectal cancer patients.</p><p><strong>Methods: </strong>Between 2012 and 2018, a total of 3,441 stage II/III colorectal cancer patients were included for analysis. To verify neuroendocrine differentiation, immunohistochemistry was performed to explore the expression of chromogranin A and synaptophysin in colorectal cancer. In addition, the difference in overall survival between groups was analyzed. A Kaplan-Meier analysis was used to determine the clinicopathological characteristics significantly correlated with survival, and a Cox proportional hazards analysis was used to identify factors independently affecting overall survival prognosis. Furthermore, the findings were validated by the Gene Expression Omnibus database.</p><p><strong>Results: </strong>Among the 3,441 stage II/III colorectal cancer patients, in comparison to patients with neuroendocrine differentiation (+), patients with neuroendocrine differentiation (+) had a poorer prognosis (p = 0.001). Furthermore, multivariate survival analysis of stage II cases revealed that tumor differentiation (p = 0.018), nerve invasion (p < 0.001), and neuroendocrine differentiation (+) (p = 0.002) were independent prognostic factors. Moreover, the prognosis of patients with neuroendocrine differentiation (+) was similar to that of patients with high-risk factors in stage II cases (p = 0.639). High chromogranin A expression was correlated with poor prognosis in stage II colorectal cancer patients in the Gene Expression Omnibus database (p < 0.001).</p><p><strong>Conclusion: </strong>The prognosis of colorectal cancer with neuroendocrine differentiation (+) was poor, especially in stage II colorectal cancer patients. Neuroendocrine differentiation might be another high-risk factor for the prognosis of stage II colorectal cancer patients.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"156-166"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors Affecting an Increase in Spleen Volume and Association of Spleen Volume Variation with the Clinical Outcomes of Atezolizumab and Bevacizumab Treatment for Hepatocellular Carcinoma: A Retrospective Analysis.","authors":"Takeshi Hatanaka, Naoto Saito, Satoru Kakizaki, Atsushi Hiraoka, Toshifumi Tada, Kazuya Kariyama, Joji Tani, Koichi Takaguchi, Ei Itobayashi, Toru Ishikawa, Hidenori Toyoda, Kazuhito Kawata, Atsushi Naganuma, Yutaka Yata, Hideko Ohama, Tomomitsu Matono, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Shinichiro Nakamura, Takashi Kumada","doi":"10.1159/000541002","DOIUrl":"10.1159/000541002","url":null,"abstract":"<p><strong>Introduction: </strong>Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev.</p><p><strong>Methods: </strong>A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics.</p><p><strong>Results: </strong>The median pretreatment SpV was 184 (130-257) cm3 and the median SpV variation was 27 (9-60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p = 0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively).</p><p><strong>Conclusion: </strong>Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"94-106"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utility of Assessing Early Tumor Shrinkage as an Efficacy Predictor in Patients with Non-Surgically Indicated or Recurrent Esophageal Cancer Treated with Nivolumab plus Ipilimumab.","authors":"Seiji Natsuki, Shigeru Lee, Hiroaki Kasashima, Yuichiro Miki, Tatsunari Fukuoka, Mami Yoshii, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Hiroaki Tanaka, Maeda Kiyoshi","doi":"10.1159/000540851","DOIUrl":"10.1159/000540851","url":null,"abstract":"<p><strong>Introduction: </strong>Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy are now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy.</p><p><strong>Methods: </strong>The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meier plots and Cox proportional hazard models.</p><p><strong>Results: </strong>The mean duration of ICI doublet administration was 5.89 months (range, 1-16 months). At first evaluation, patients who exhibited no tumor progression >20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience.</p><p><strong>Conclusion: </strong>ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS >0% could be a deciding factor for continuing ICI doublet therapy.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"167-178"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-08-19DOI: 10.1159/000540515
Franziska Maria Kraus, Alexander Traut, Georg Nilius, Jan Volmerig, Andreas Koziorowski, Imke Stöver, Florian Grabellus, Michael Stahl, Daniel C Christoph
{"title":"Pulmonary Adenocarcinoma with Enteric Differentiation without TTF-1 Expression Is a Very Rare Subtype with Limited Treatment Options and Poor Prognosis.","authors":"Franziska Maria Kraus, Alexander Traut, Georg Nilius, Jan Volmerig, Andreas Koziorowski, Imke Stöver, Florian Grabellus, Michael Stahl, Daniel C Christoph","doi":"10.1159/000540515","DOIUrl":"10.1159/000540515","url":null,"abstract":"<p><strong>Introduction: </strong>Pulmonary adenocarcinoma with enteric differentiation (PAED) without thyroid transcription factor-1 (TTF-1) expression is an extremely rare variant of lung cancer. Due to its rarity, few clinicopathological and molecular studies have been performed on PAED, particularly in Caucasian patients. Therefore, it is necessary to obtain clinicopathological data of Caucasian PAED patients without TTF-1 expression, their systemic therapy options, and the efficacy of their systemic treatment.</p><p><strong>Methods: </strong>We examined the clinicopathological features of 121 cases of TTF-1-negative pulmonary adenocarcinoma at a certified German lung cancer center including 79 cases without a PAED and 42 cases with a PAED, compared these subgroups, and investigated patients' response to chemotherapy and immunotherapy as first-line treatment. By using endoscopy and/or a PET-CT, a primary adenocarcinoma of the digestive tract was excluded in all PAED patients.</p><p><strong>Results: </strong>A comparison of clinicopathological data of TTF-1-negative PAED and non-PAED patients revealed a significantly lower frequency of high programmed death receptor ligand 1 (PD-L1) expression in PAED resulting in the lack of single-agent immunotherapy (p = 0.032) in this subgroup. Frequencies of an activating Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutation were high in both groups (46.7% and 50.0%), but G12C gene mutations were seldomly noted (in 6.7% and 18.5% of patients with evaluable data). Median overall survival (OS) was poor in both groups (10 and 12 months). The majority of PAED patients received platinum-based and taxane-containing chemotherapy or chemo-/immunotherapy with an objective response rate (ORR) of 31.6% and a disease control rate of 57.9%. Median progression-free survival (PFS) and OS of PAED patients with systemic therapy were very poor (3.9 months and 5.9 months).</p><p><strong>Conclusions: </strong>Caucasian patients with TTF-1 negative PAED have a poor prognosis with a reduced ORR to standard first-line systemic therapy and short survival times (PFS and OS).</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"179-191"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-07-31DOI: 10.1159/000540650
Ahmed Badr, Maria Benkhadra, Basel Elsayed, Omar Metwally, Mohamed Elhadary, Amgad Mohamed Elshoeibi, Rola Ghasoub, Raghad Mohamed Elshoeibi, Salem Alshemmari, Mervat Mattar, Khalil Alfarsi, Mohamed Yassin
{"title":"Chronic Lymphocytic Leukemia in Pregnancy: A Review of the Available Literature and the Pharmacological Challenges in Management.","authors":"Ahmed Badr, Maria Benkhadra, Basel Elsayed, Omar Metwally, Mohamed Elhadary, Amgad Mohamed Elshoeibi, Rola Ghasoub, Raghad Mohamed Elshoeibi, Salem Alshemmari, Mervat Mattar, Khalil Alfarsi, Mohamed Yassin","doi":"10.1159/000540650","DOIUrl":"10.1159/000540650","url":null,"abstract":"<p><strong>Background: </strong>Chronic lymphocytic leukemia (CLL) is a rare hematologic malignancy to occur in pregnancy, with an estimated incidence of 1 in 75,000 pregnancies. Pregnant women with CLL face increased susceptibility to infections, due to a weakened immune system. Higher risks of fetal malformations and death are associated with CLL treatment during pregnancy, emphasizing the need for careful consideration and management in these cases.</p><p><strong>Summary: </strong>This review aimed to summarize the current evidence regarding the diagnosis, prognosis, and treatment of CLL in pregnant cases. A comprehensive search strategy was employed across multiple databases, yielding 14 case reports for inclusion. The cases were divided based on CLL diagnosis onset, either before or during pregnancy. Our results showed that patients diagnosed during pregnancy (n = 5) were mostly asymptomatic at diagnosis, with management ranging from supportive care to leukapheresis and transfusions. Postpartum treatment varied, with some patients requiring no additional therapy and others receiving chemotherapy. Pregnancy outcomes were generally favorable, with most neonates born healthy at term. However, one case of Richter transformation resulted in maternal death despite treatment. Among patients with pre-existing CLL (n = 9), the majority experienced an indolent course during pregnancy, with only supportive care required. A few cases necessitated treatment due to progressive disease or complications, including chemotherapy, leukapheresis, and splenectomy.</p><p><strong>Key messages: </strong>This review highlights the heterogeneous nature of CLL in pregnancy and the importance of individualized management based on disease severity, gestational age, and maternal-fetal risks. Close monitoring, supportive care, and a multidisciplinary approach are essential for optimizing outcomes in this rare and complex clinical scenario.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"56-68"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-09-20DOI: 10.1159/000540977
Wei Fang, Shan Chen, Di Wan, Yanhui Peng, Xiaoqin Yang
{"title":"Identification and Validation of an Invasion-Related Disease-Free Survival Prognostic Model for Tongue Squamous Cell Carcinoma.","authors":"Wei Fang, Shan Chen, Di Wan, Yanhui Peng, Xiaoqin Yang","doi":"10.1159/000540977","DOIUrl":"10.1159/000540977","url":null,"abstract":"<p><strong>Introduction: </strong>Tongue squamous cell carcinoma (TSCC) <underline>is</underline> a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients.</p><p><strong>Methods: </strong>We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.</p><p><strong>Results: </strong>A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line.</p><p><strong>Conclusion: </strong>This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"237-252"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interleukin-7 Risk Allele, Lymphocyte Counts, and Autoantibodies for Prediction of Risk of Immune-Related Adverse Events in Patients Receiving Atezolizumab plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma.","authors":"Hitomi Takada, Leona Osawa, Yasuyuki Komiyama, Masaru Muraoka, Yuichiro Suzuki, Mitsuaki Sato, Shoji Kobayashi, Takashi Yoshida, Shinichi Takano, Shinya Maekawa, Nobuyuki Enomoto","doi":"10.1159/000540648","DOIUrl":"10.1159/000540648","url":null,"abstract":"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab (AB) therapy was the effective immune checkpoint inhibitor (ICI) for unresectable hepatocellular carcinoma (u-HCC). However, immune-related adverse events (irAEs) are common in patients receiving ICI therapies. Our research aimed to explore the risk factors for irAE development, with attention to interleukin-7 (IL-7) risk alleles, lymphocyte counts, and autoantibodies.</p><p><strong>Methods: </strong>Seventy-six patients receiving AB therapy for u-HCC were recruited. Single nucleotide polymorphism genotyping was done for the analysis of rs16906115 polymorphism near IL-7-expressing genes using 20 μL of stored buffy coat at baseline. The association between IL-7 risk alleles, lymphocyte counts, autoantibodies, and irAE development was investigated.</p><p><strong>Results: </strong>irAEs were found in 14 (18%) patients. The incidence of irAEs did not differ significantly between the groups showing IL-7 AG/AA and the GG group (p = 0.72). The incidence in the group with a lymphocyte count of 1,130/µL or more at baseline was higher than in that with a value below 1,130/µL (p = 0.0093). The group showing IL-7 AG/AA or lymphocyte count >1,130/μL had a higher irAE prevalence rate than the others (p = 0.019). IL-7 AG/AA or lymphocyte count >1,130/μL and positivity for autoantibodies at baseline were the prognostic factors for irAE development. irAE incidence could be stratified using a combination of IL-7 AG/AA or lymphocyte counts ≥1,130/µL and positive autoantibodies (p = 0.016).</p><p><strong>Conclusion: </strong>Patients with IL-7 risk alleles, high lymphocyte counts, and autoantibodies at baseline may require careful monitoring for irAE development.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"37-47"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncologyPub Date : 2025-01-01Epub Date: 2024-08-14DOI: 10.1159/000540887
Jan Dimberg, Levar Shamoun, Kristin Af Geijerstam, Kalle Landerholm, Dick Wågsäter
{"title":"Significance of Gene Polymorphism and Gene Expression of BACE2 in Swedish Patients with Colorectal Cancer.","authors":"Jan Dimberg, Levar Shamoun, Kristin Af Geijerstam, Kalle Landerholm, Dick Wågsäter","doi":"10.1159/000540887","DOIUrl":"10.1159/000540887","url":null,"abstract":"<p><strong>Introduction: </strong>β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC.</p><p><strong>Methods: </strong>A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue.</p><p><strong>Results: </strong>Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer.</p><p><strong>Conclusion: </strong>In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"48-55"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}