Cancer Biomarkers
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PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255580
Emanuele Caselli ◽  
Cristina Pelliccia ◽  
Valeria Teti ◽  
Guido Bellezza ◽  
Martina Mandarano ◽  

Purpose Decades of quality control efforts have raised the standards of immunohistochemistry (IHC), the principle method used for biomarker testing in breast cancer; however, computational pathology and reverse transcription quantitative PCR (RT-qPCR) may also hold promise for additional substantial improvements. Methods Herein, we investigated discrepancies in the assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki67 comparing routinely obtained IHC (and FISH) data (ORI) with the results of manual (REV) and semi-automated (DIA) re-evaluation of the original IHC slides and then with RNA expression data from the same tissue block using the MammaTyper® (MT) gene expression assay. Results Correlation for ER and PR was high between ORI IHC and the other three study methods (REV, DIA and RT-qPCR). For HER2, 10 out of 96 discrepant cases can be detected between ORI and REV that involved at least one call in the equivocal category (except for one case). For Ki67, 22 (29.1%) cases were categorized differently by either REV alone (n = 17), DIA alone (n = 15) or both (n = 10) and 28 cases (29.2%) for RT-qPCR. Most of the discrepant Ki67 cases changed from low to high between the original and following assessment and belonged to the intermediate Ki67 expression range (between 9 and 30%). Conclusions Determination of the breast cancer biomarkers ER, PR, HER2 and Ki67 at the mRNA level shows high degree of correlation with IHC and compares well with correlations between original with subsequent independent manual or semi-automated IHC assessments. The use of methods with wider dynamic range and higher reproducibility such as RT-qPCR may offer more precise assessment of endocrine responsiveness, improve Ki67 standardization and help resolve HER2 cases that remain equivocal or ambiguous by IHC/FISH. In summary, our findings seem to configure RT-qPCR as a complementary method to be used in cases of either equivocal results or presenting, at the traditional determination assays, biomarkers expressions close to the cut-off values.

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Duo Yun ◽  
Zhirong Yang

LncRNAs (long noncoding RNAs) are closely associated with genome instability. However, the identification of lncRNAs related to the genome instability and their relationship with the prognosis and clinical signature of cancer remains to be explored. In this paper, we analyzed differential lncRNA expression based on the somatic mutation profiles of colon cancer patients from TCGA database and finally identified 153 lncRNAs that are associated with genome instability in colon cancer. Taking four lncRNAs from these 153, we established a genome-instability-related prognostic signature (GIRlncPSig). By applying the GIRlncPSig, we calculated a risk score for each patient, and using their risk scores, we divided them into low- and high-risk groups. We found that the prognosis between the two risk groups was significantly different, and the results were further verified in different independent patient cohorts. Moreover, we observed that the GIRlncPSig was related to somatic mutation rates in colon cancer, indicating that it may be a potential means of measuring genome instability levels in colon cancer. We also revealed that the GIRlncPSig was correlated with BRAF and DPYD mutation rates and that it may be a potential mutation marker for the BRAF and DPYD gene. In summary, we constructed a genome-instability-related lncRNA prognostic signature (GIRlncPSig), which has a significant effect on prognosis prediction and may allow for the discovery of new colon cancer biomarkers.

Jyoti Singh ◽  
Abha Meena

Background: Phytochemicals are used to treat lung cancer in contemporary and traditional medicine. The limitations of known chemotherapeutic drugs such as non-specificity, resistance, and toxicity restrict their use for lung cancer treatment. Therefore, the search for target-specific novel entities is required continuously. Objective: Linalool, a monoterpene alcohol that possesses antiviral, anti-inflammatory, and antibacterial properties, is present in sweet basil, laurel, jasmine, rosewood and lavender. Previous reports revealed its anticancer potential against colon, breast and liver cancer. In this study, linalool's efficacy in targeting biomarkers associated with different lung cancer stages has been investigated Methods: The insilico molecular docking analysis was used to explore drug receptor interaction, and further, linalools cytotoxicity potential was evaluated on lung adenocarcinoma cell line (A549). The toxicity profiling of linalool was done by ADMET analysis. Results: In results Linalool revealed an excellent binding affinity with the selected targets. It showed the highest interaction with BRAF with binding energy -5.6 kcal/mol. Furthermore, it successfully interacts within the binding pocket of BRAF, similar to its inhibitor (Sorafenib). In MTT analysis, linalool significantly reduces the percent viability (IC30 474.94 ± 43.12, 379.33 ± 49.5, and 183.77 ± 66.7 µM in A549 cell lines for 24, 48, and 72 h respectively. Conclusion: These results concluded that linalool possesses chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation.

2021 ◽  
Vol 22 (18) ◽  
pp. 9692
Loredana Moro

Pancreatic cancer is an aggressive disease with poor prognosis. Only about 15–20% of patients diagnosed with pancreatic cancer can undergo surgical resection, while the remaining 80% are diagnosed with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In these cases, chemotherapy and radiotherapy only confer marginal survival benefit. Recent progress has been made in understanding the pathobiology of pancreatic cancer, with a particular effort in discovering new diagnostic and prognostic biomarkers, novel therapeutic targets, and biomarkers that can predict response to chemo- and/or radiotherapy. Mitochondria have become a focus in pancreatic cancer research due to their roles as powerhouses of the cell, important subcellular biosynthetic factories, and crucial determinants of cell survival and response to chemotherapy. Changes in the mitochondrial genome (mtDNA) have been implicated in chemoresistance and metastatic progression in some cancer types. There is also growing evidence that changes in microRNAs that regulate the expression of mtDNA-encoded mitochondrial proteins (mitomiRs) or nuclear-encoded mitochondrial proteins (mitochondria-related miRs) could serve as diagnostic and prognostic cancer biomarkers. This review discusses the current knowledge on the clinical significance of changes of mtDNA, mitomiRs, and mitochondria-related miRs in pancreatic cancer and their potential role as predictors of cancer risk, as diagnostic and prognostic biomarkers, and as molecular targets for personalized cancer therapy.

Burak Dik ◽  
Devran Coskun ◽  
Ayşe Er

Background: Colon cancers are among the three major cancer types that result in death. The research for effective treatment continues. Objective: The aim of this study is to determine the effects of Tarantula cubensis alcoholic extract (TCAE) and Nerium oleander (NO) distillate on the levels of midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase 3 in liver and colon tissues of experimentally induced colon cancer in rats. Method: The liver and colon tissues of the rats were divided into Control, Colon Cancer (AZM), AZM+TCAE and AZM+NO groups and they were homogenized. The levels of midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase 3 in the colon and liver tissues were measured by ELISA kits. Results: All parameters levels of colon and liver tissues in the AZM group were generally higher (p<0.05) than the Control group. TCAE and NO prevented (p<0.05) the increases in midkine, TGF-β, VEGF, AFP, COX-2, IGF and caspase-3 levels in the colon. NO prevented increase of all parameters except for IGF level, while TCAE prevented (p<0.05) the increase of all values apart from COX-2 and IGF levels in the liver. Conclusion: NO and TCAE may prevented at the specified marker levels of colon in the AZM induced colon cancer. The increases the level of parameters in the liver are not as severe as in the colon, due to the 18-week study period may not be sufficient for liver metastasis formationIn the future molecular studies should be done to determine the mechanisms and pathways of them more clearly.

2021 ◽  
Vol 27 (9) ◽  
Tarun Tarun ◽  
Paramjot Singh ◽  
Harmandar Kaur ◽  
Gurleen Kaur Walia ◽  
Deep Kamal Kaur Randhawa ◽  

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4346
Kim van der Zande ◽  
Wim J. G. Oyen ◽  
Wilbert Zwart ◽  
Andries M. Bergman

Radium-223 dichloride ([223Ra]RaCl2; Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers.

2021 ◽  
Vol 11 (17) ◽  
pp. 7835
Anna Sankiewicz ◽  
Tomasz Guszcz ◽  
Ewa Gorodkiewicz

The ubiquitin–proteasome system (UPS) participates in the degradation of proteins which play an important role in regulating the cell cycle, apoptosis, and angiogenesis, as well as in the immune system. These processes are important in carcinogenesis. Transitional cell carcinoma (TCC) is one of the predominant types of bladder cancer. The relationship between the ubiquitin–proteasome system and cancer progression has become a topic of increasing interest among researchers. In this work, we propose an application of surface plasmon resonance imaging (SPRi)-based biosensors for the detection of 20S proteasome and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) in the blood serum and urine of patients with TCC. The aim of the study was to determine 20S proteasome and UCH-L1 concentrations and to correlate the results with clinicopathological parameters. The group of subjects consisted of 82 patients with confirmed TCC, in addition to a control group of 27 healthy volunteers. It was found that 20S proteasome and UCH-L1 concentrations were significantly elevated in both the serum and urine of TCC patients, compared with the healthy subjects. There was a correlation between 20S proteasome concentrations in serum and urine, as well as between serum proteasome and UCH-L1 concentration. The SPRi biosensor sensitive to 20S proteasome using PSI inhibitor as the receptor, and the SPRi biosensor sensitive to the UCH-L1 protein using the protein-specific antibody as the receptor is suitable for the determination of 20S proteasome and UCH-L1 in body fluids and can serve as useful tools in the investigation of cancer biomarkers.

Metabolites ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 566
Andrea Ragusa ◽  
Pietrina Romano ◽  
Marcello Salvatore Lenucci ◽  
Emanuela Civino ◽  
Daniele Vergara ◽  

Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, ROC analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.

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