Cancer Biomarkers - Volume 33, issue 1

Authors: Chatterjee, Annesha | Khadirnaikar, Seema | Shukla, Sudhanshu

Article Type: Research Article

Abstract: BACKGROUND: An increasing number of studies are indicating that the stemness phenotype is a critical determinant of the Lung adenocarcinoma (LUAD) patient’s response. Thus, it is crucial to identify novel biomarkers for stemness determination. OBJECTIVE: Here, we aim to develop a robust LncRNAs based prognostic signature with a stemness association for the LUAD patients. METHODS: RNA-seq and clinical data were downloaded from the existing database. The data were analysed using Cox regression, KM-plot, GSEA, and T -test. RESULTS: Initially, we used the TCGA dataset to characterize the stemness …phenotype in LUAD. The commonly expressed LncRNAs in TCGA and MCTP cohort were then used as input for the Cox-regression analysis. The top three LncRNAs were selected to build a prognostic model, which was the best prognosticator in multivariate analysis with stage and previously published prognosticators. The characterization of poor surviving patients using various analysis showed high stemness properties and low expression of differentiation markers. Furthermore, we validated the prognostic score in an independent MCTP cohort of patients. In the MCTP cohort, prognostic score significantly predicted survival independent of stage and previous prognosticators. CONCLUSION: Taken together, in this study, we have developed and validated a new prognostic score associated with the stemness phenotype. Show more

Keywords: Lung cancer, biomarker, prognostic model, stemness

DOI: 10.3233/CBM-200687

Citation: Cancer Biomarkers, vol. 33, no. 1, pp. 131-142, 2022

Authors: Foda, Abd AlRahman Mohammad | Alamer, Haitham Abdulkarem | Ikram, Nadeem | Helali, Hadi Abdulhadi | Fayad, Fayza Sami | Hussian, Sara Waleed | Abdelwahab, Khaled | Akl, Tamer | Emarah, Ziad | Ramez, Ahmed M.

Article Type: Research Article

Abstract: BACKGROUND: CD10 and CD15 expression has been reported in several tumors. Whether CD10 and CD15 have a role in colorectal mucinous and signet ring adenocarcinoma (MSA) tumorigenesis is not yet known. OBJECTIVE: We aimed to investigate the role of CD10 and CD15 expression in mucinous colorectal adenoma-carcinoma sequence (ACS) and determine if there is any clinical and prognostic significance associated with their expression. METHODS: Seventy-five cases of colorectal MSA, and 9 cases of adenoma samples were collected. Manual TMA blocks were constructed and immunohistochemistry for CD10 and CD15 was done. RESULTS: …Compared to adenomas, CD15 expression was significantly higher in MSA (p = 0.002), in contrast to CD10 expression. CD15 positivity was significantly associated with microsatellite stable (MSS) tumors (p = 0.018). The association between CD10 positivity and fungating tumor growth showed marginal significance. Unlike CD10, CD15 positivity showed significant association with overall survival of colorectal MSA patients. CONCLUSIONS: CD15 expression seems to have a role in mucinous colorectal ACS, with significant impact on the survival of MSA patients. Further studies are suggested to identify any genetic alterations that may underlie a potential association with disease progression. Show more

Keywords: CD10, CD15, mucinous, colorectal, carcinoma

DOI: 10.3233/CBM-210067

Citation: Cancer Biomarkers, vol. 33, no. 1, pp. 143-150, 2022

Authors: Murakami, Kaoru | Kamat, Ashish M. | Dai, Yunfeng | Pagano, Ian | Chen, Runpu | Sun, Yijun | Gupta, Amit | Goodison, Steve | Rosser, Charles J. | Furuya, Hideki

Article Type: Research Article

Abstract: BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG), a live attenuated tuberculosis vaccine that acts as a non-specific immune system stimulant, is the most effective adjuvant treatment for patients with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC). However, to date, there are no reliable tests that are predictive of BCG treatment response. In this study, we evaluated the performance of Oncuria TM , a bladder cancer detection test, to predict response to intravesical BCG. METHODS: Oncuria TM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 64 …subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The Oncuria TM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. The ability of the test to identify those patients in whom BCG is ineffective against tumor recurrence was tested. Predictive models were derived using supervised learning and cross-validation analyses. Model performance was assessed using ROC curves. RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved an AUROC 0.89 [95% CI: 0.80–0.99], outperforming any single biomarker, with a test sensitivity of 81.8% and a specificity of 84.9%. Hazard ratio analysis revealed that patients with higher urinary levels of ANG, CA9 and MMP10 had a significantly higher risk of disease recurrence. CONCLUSIONS: Monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. With further study, the multiplex Oncuria TM test may be applicable for the clinical evaluation of bladder cancer patients considering intravesical BCG treatment. Show more

Keywords: Biomarkers, bladder cancer, multiplex, protein, BCG

DOI: 10.3233/CBM-210221

Citation: Cancer Biomarkers, vol. 33, no. 1, pp. 151-157, 2022

Authors: Dick, I.M. | Lee, Y.C.G. | Cheah, H.M. | Miranda, A. | Robinson, B.W.S. | Creaney, J.

Article Type: Research Article

Abstract: BACKGROUND: Pleural mesothelioma is a deadly asbestos induced cancer. Less than 10% of mesothelioma patients survive 5 years post diagnosis. However survival can range from a few months to a number of years. Accurate prediction of survival is important for patients to plan for their remaining life, and for clinicians to determine appropriate therapy. One unusual feature of mesothelioma is that patients frequently present with tumor-associated pleural effusions early in the course of the disease. OBJECTIVE: To study whether cells and molecules present in pleural effusions provide prognostic information for mesothelioma. METHODS: We profiled …the cellular constituents and concentrations of 40 cytokines, chemokines and cellular factors (collectively “soluble factors”) involved in inflammatory and immune signalling pathways in pleural effusion samples from 50 mesothelioma patients. Associations with survival were evaluated by Cox proportional hazards regression methods. Results for the two soluble factors most significantly and independently associated with survival were validated in an independent set of samples (n = 51) using a separate assay system. RESULTS: Survival analysis revealed that IL8, IL2Ra (CD25) and PF4 were independent determinants of a more negative prognosis in mesothelioma patients, independent of other known prognostic factors. Lipocalin2 and IL4 were associated with better prognosis. CONCLUSIONS: This study demonstrates that pleural effusions rich in a range of soluble factors are associated with poor prognosis. These findings will enhance our ability to prognosticate outcomes in mesothelioma patients. Show more

Keywords: Pleural mesothelioma, pleural effusions, cytokines, chemokines, cellular factors, prognosis

DOI: 10.3233/CBM-210280

Citation: Cancer Biomarkers, vol. 33, no. 1, pp. 159-169, 2022