Cancer Biomarkers - Volume 34, issue 4

Authors: Kim, Jae Hyeong | Youn, Yuna | Lee, Jong-Chan | Kim, Jaihwan | Ryu, Ji Kon | Hwang, Jin-Hyeok

Article Type: Research Article

Abstract: Pancreatic cancer is an aggressive and lethal cancer with the highest mortality rate. Hence, the development of new targeting and innovative treatment strategies is needed. Recent studies reported that the histone chaperone anti-silencing function 1B (ASF1B ) can be used as a diagnosis and prognosis cancer biomarker. However, functional studies of ASF1B in pancreatic cancer have not been performed. This study compared expression levels of ASF1B in pancreatic cancer specimens with those of normal tissues using publicly available online databases. We found that ASF1B was commonly overexpressed in pancreatic cancer specimens, which is associated with poor prognosis. ASF1B …downregulation in pancreatic cancer cells reduced their colony formation, proliferation, migration, and invasion abilities, and inhibited MMP9 activity. Furthermore, ASF1B expression downregulation increased cell cycle S-phase arrest and DNA damage though activation of the checkpoint kinases Chk1 and Chk2 pathways. Additionally, increased caspase (caspases-3 and -9) activation and PARP cleavage led to enhanced caspase-dependent apoptosis and improved cisplatin sensitivity. Collectively, our results indicate that ASF1B may serve as a potential biomarker of pancreatic cancer and a novel therapeutic target. Show more

Keywords: ASF1B, pancreatic cancer, cisplatin, biomarker, therapeutic target

DOI: 10.3233/CBM-210490

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 647-659, 2022

Authors: Druy, A.E. | Tsaur, G.A. | Shorikov, E.V. | Tytgat, G.A.M. | Fechina, L.G.

Article Type: Research Article

Abstract: BACKGROUND: Molecular and clinical diversity of neuroblastomas is notorious. The activating TERT rearrangements have been associated with dismal prognosis. Suppression of miR-128-3p may complement and enhance the adverse effects of TERT overexpression. OBJECTIVE: The study aimed at evaluation of prognostic significance of the miR-128-3p/TERT expression in patients with primary neuroblastoma. METHODS: RNA samples isolated from fresh-frozen tumor specimens (n = 103) were reverse transcribed for evaluation of miR-128-3p and TERT expression by qPCR. The normalized expression levels were tested for correlations with the event-free …survival (EFS). ROC-analysis was used to establish threshold expression levels (TLs) for the possible best prediction of the outcomes. The median follow-up was 57 months. RESULTS: Both TERT overexpression and miR-128-3p downregulation were independently associated with superior rates of adverse events (p = 0.027, TL = - 2.32 log 10 and p = 0.080, TL = - 1.33 log 10 , respectively). The MYCN single-copy patients were stratified into groups based on the character of alterations in expression of the studied transcripts. Five-year EFS in the groups of patients with elevated TERT /normal miR-128-3p expression and normal TERT /reduced miR-128-3p expression were 0.74 ± 0.08 and 0.60 ± 0.16, respectively. The patients with elevated TERT /reduced miR-128-3p expression had the worst outcomes, with 5-year EFS of 0.40 ± 0.16 compared with 0.91 ± 0.06 for the patients with unaltered levels of both transcripts (p < 0.001). Cumulative incidence of relapse/progression for the groups constituted 0.23 ± 0.08, 0.40 ± 0.16, 0.60 ± 0.16 and 0.09 ± 0.06, respectively. Moreover, the loss of miR-128-3p was qualified as independent adverse predictor which outperformed the conventional clinical and genetic risk factors in the multivariate Cox regression model of EFS. CONCLUSIONS: Combined expression levels of miR-128-3p and TERT represent a novel prognostic biomarker for neuroblastoma. Show more

Keywords: Neuroblastoma, miR-128-3p, expression, prognosis

DOI: 10.3233/CBM-210414

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 661-671, 2022

Authors: Murakami, Atsushi | Amano, Tsukuru | Yoshino, Fumi | Kita, Hiroko | Moritani, Suzuko | Murakami, Takashi | Chano, Tokuhiro

Article Type: Research Article

Abstract: BACKGROUND: Ovarian clear cell carcinomas (OCCCs) have been recurrent and refractory among the present treatments, so novel therapeutics are urgently needed. OBJECTIVE: The present study accumulates the proof of concept to examine the feasibility of RDH10 as a therapeutic target for treating OCCCs. METHODS: Immunohistochemically, RDH10 expression was evaluated in 111 primary epithelial ovarian cancers, including 55 OCCCs, 31 ovarian endometrioid carcinomas and 25 ovarian serous carcinomas. The spherogenecity provoked by RDH10 was evaluated in OCCC cells. To analyze whether RDH10 promotes carbohydrate storage via the vitamin A-gluconeogenesis pathway, phosphoenolpyruvate carboxykinase 1 (PCK1) …protein levels and intracellular carbohydrate content were measured in response to modified RDH10 expression. RESULTS: Abundant RDH10 was expressed specifically in OCCCs. RDH10 promoted spherogenecity and intracellular carbohydrate storage via modulation of PCK1 expression in OCCC cells. CONCLUSIONS: In the present study, abundant RDH10 contributed to cancer cell stemness and intracellular carbohydrate storage in OCCCs. RDH10 is a potentially, new therapeutic candidate for treating OCCC cases. Show more

Keywords: Ovarian clear cell carcinoma, RDH10, retinoids, gluconeogenesis, carbohydrates

DOI: 10.3233/CBM-210435

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 673-679, 2022

Authors: Mueller, Alex N. | Morrisey, Samantha | Miller, Hunter A. | Hu, Xiaoling | Kumar, Rohit | Ngo, Phuong T. | Yan, Jun | Frieboes, Hermann B.

Article Type: Research Article

Abstract: BACKGROUND: Although advances have been made in cancer immunotherapy, patient benefits remain elusive. For non-small cell lung cancer (NSCLC), monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have shown survival benefit compared to chemotherapy. Personalization of treatment would be facilitated by a priori identification of patients likely to benefit. OBJECTIVE: This pilot study applied a suite of machine learning methods to analyze mass cytometry data of immune cell lineage and surface markers from blood samples of a small cohort (n = 13) treated with Pembrolizumab, Atezolizumab, Durvalumab, …or Nivolumab as monotherapy. METHODS: Four different comparisons were evaluated between data collected at an initial visit (baseline), after 12-weeks of immunotherapy, and from healthy (control) samples: healthy vs patients at baseline, Responders vs Non-Responders at baseline, Healthy vs 12-week Responders, and Responders vs Non-Responders at 12-weeks. The algorithms Random Forest, Partial Least Squares Discriminant Analysis, Multi-Layer Perceptron, and Elastic Net were applied to find features differentiating between these groups and provide for the capability to predict outcomes. RESULTS: Particular combinations and proportions of immune cell lineage and surface markers were sufficient to accurately discriminate between the groups without overfitting the data. In particular, markers associated with the B-cell phenotype were identified as key features. CONCLUSIONS: This study illustrates a comprehensive machine learning analysis of circulating immune cell characteristics of NSCLC patients with the potential to predict response to immunotherapy. Upon further evaluation in a larger cohort, the proposed methodology could help guide personalized treatment selection in clinical practice. Show more

Keywords: lung cancer, immunotherapy, machine learning, immune cells, cell markers

DOI: 10.3233/CBM-210529

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 681-692, 2022

Authors: Vance, Krysten | Alitinok, Alphan | Winfree, Seth | Jensen-Smith, Heather | Swanson, Benjamin J. | Grandgenett, Paul M. | Klute, Kelsey A. | Crichton, Daniel J. | Hollingsworth, Michael A.

Article Type: Correction

DOI: 10.3233/CBM-220901

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 693-693, 2022

Article Type: Retraction

DOI: 10.3233/CBM-220951

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 695-695, 2022

Article Type: Retraction

DOI: 10.3233/CBM-229002

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 697-697, 2022

Article Type: Retraction

DOI: 10.3233/CBM-229004

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 699-699, 2022

Article Type: Retraction

DOI: 10.3233/CBM-219903

Citation: Cancer Biomarkers, vol. 34, no. 4, pp. 701-701, 2022