Topical Collection "Cancer Biomarkers"

Editor

Dr. Carlos S. Moreno
E-Mail Website
Collection Editor
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Interests: Prostate Cancer; Breast Cancer; Bioinformatics; Genomics; Transcription; Biomarkers
Special Issues and Collections in MDPI journals

Topical Collection Information

Dear Colleagues,

Biomarkers are playing an ever-increasingly important role in the diagnosis, treatment, and management of cancer patients. Advances in detection technologies, including next generation sequencing, circulating tumor cells, and multicolor flow cytometry, among others, have enabled scientists and clinicians to gain greater insights into the molecular mechanisms that underlie the pathologies of a variety of malignancies. Furthermore, targeted precision therapies often require the identification of subsets of patients who will benefit from these therapies, and cancer biomarkers are essential to obtaining FDA approval for many drugs under development and investigation. Additionally, biomarkers are currently in clinical practice to identify patients with favorable prognoses who can safely avoid overtreatment. Nevertheless, challenges remain in development of new non-invasive biomarkers with greater sensitivity, specificity, and clinical utility. This Topical Collection will review the current state of cancer biomarker development and the prospects for improving cancer care with new technologies and biomarkers to improve cancer patient diagnoses, management, and outcomes.

Dr. Carlos S. Moreno
Guest Editor

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Keywords

  • Biomarkers
  • Precision Medicine
  • Diagnosis
  • Prognosis
  • Liquid Biopsy
  • Companion Diagnostics

Published Papers (15 papers)

2019

Open AccessArticle
Notch Signaling Molecules as Prognostic Biomarkers for Acute Myeloid Leukemia
Cancers 2019, 11(12), 1958; https://doi.org/10.3390/cancers11121958 - 06 Dec 2019
Abstract
The role of Notch signaling in acute myeloid leukemia (AML) is still under investigation. We have previously shown that high levels of Notch receptors and ligands could interfere with drug response. In this study, the protein expression of 79 AML blast samples collected [...] Read more.
The role of Notch signaling in acute myeloid leukemia (AML) is still under investigation. We have previously shown that high levels of Notch receptors and ligands could interfere with drug response. In this study, the protein expression of 79 AML blast samples collected from newly diagnosed patients was examined through flow cytometry. Gamma-secretase inhibitors were used in AML mouse xenograft models to evaluate the contribution of Notch pharmacological inhibition to mouse survival. We used univariate analysis for testing the correlation and/or association between protein expression and well-known prognostics markers. All the four receptors (Notch1–4) and some ligands (Jagged2, DLL-3) were highly expressed in less mature subtypes (M0–M1). Notch3, Notch4, and Jagged2 were overexpressed in an adverse cytogenetic risk group compared to good cytogenetic risk patients. Chi-square analysis revealed a positive association between the complete remission rate after induction therapy and weak expression of Notch2 and Notch3. We also found an association between low levels of Notch4 and Jagged2 and three-year remission following allogeneic stem cell transplantation (HSCT). Accordingly, Kaplan–Meier analysis showed improved OS for patients lacking significant expression of Notch4, Jagged2, and DLL3. In vivo experiments in an AML mouse model highlighted both improved survival and a significant reduction of leukemia cell burden in the bone marrow of mice treated with the combination of Notch pan-inhibitors (GSIs) plus chemotherapy (Ara-C). Our results suggest that Notch can be useful as a prognostic marker and therapeutic target in AML. Full article
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Open AccessArticle
A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms
Cancers 2019, 11(12), 1872; https://doi.org/10.3390/cancers11121872 - 26 Nov 2019
Abstract
Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to [...] Read more.
Although mammography is the gold standard for breast cancer screening, the high rates of false-positive mammograms remain a concern. Thus, there is an unmet clinical need for a non-invasive and reliable test to differentiate between malignant and benign breast lesions in order to avoid subjecting patients with abnormal mammograms to unnecessary follow-up diagnostic procedures. Serum samples from 116 malignant breast lesions and 64 benign breast lesions were comprehensively profiled for 2,083 microRNAs (miRNAs) using next-generation sequencing. Of the 180 samples profiled, three outliers were removed based on the principal component analysis (PCA), and the remaining samples were divided into training (n = 125) and test (n = 52) sets at a 70:30 ratio for further analysis. In the training set, significantly differentially expressed miRNAs (adjusted p < 0.01) were identified after correcting for multiple testing using a false discovery rate. Subsequently, a predictive classification model using an eight-miRNA signature and a Bayesian logistic regression algorithm was developed. Based on the receiver operating characteristic (ROC) curve analysis in the test set, the model could achieve an area under the curve (AUC) of 0.9542. Together, this study demonstrates the potential use of circulating miRNAs as an adjunct test to stratify breast lesions in patients with abnormal screening mammograms. Full article
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Open AccessArticle
ALDH1A2 Is a Candidate Tumor Suppressor Gene in Ovarian Cancer
Cancers 2019, 11(10), 1553; https://doi.org/10.3390/cancers11101553 - 14 Oct 2019
Abstract
Aldehyde dehydrogenase 1 family member A2 (ALDH1A2) is a rate-limiting enzyme involved in cellular retinoic acid synthesis. However, its functional role in ovarian cancer remains elusive. Here, we found that ALDH1A2 was the most prominently downregulated gene among ALDH family members in ovarian [...] Read more.
Aldehyde dehydrogenase 1 family member A2 (ALDH1A2) is a rate-limiting enzyme involved in cellular retinoic acid synthesis. However, its functional role in ovarian cancer remains elusive. Here, we found that ALDH1A2 was the most prominently downregulated gene among ALDH family members in ovarian cancer cells, according to complementary DNA microarray data. Low ALDH1A2 expression was associated with unfavorable prognosis and shorter disease-free and overall survival for ovarian cancer patients. Notably, hypermethylation of ALDH1A2 was significantly higher in ovarian cancer cell lines when compared to that in immortalized human ovarian surface epithelial cell lines. ALDH1A2 expression was restored in various ovarian cancer cell lines after treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Furthermore, silencing DNA methyltransferase 1 (DNMT1) or 3B (DNMT3B) restored ALDH1A2 expression in ovarian cancer cell lines. Functional studies revealed that forced ALDH1A2 expression significantly impaired the proliferation of ovarian cancer cells and their invasive activity. To the best of our knowledge, this is the first study to show that ALDH1A2 expression is regulated by the epigenetic regulation of DNMTs, and subsequently that it might act as a tumor suppressor in ovarian cancer, further suggesting that enhancing ALDH1A2-linked signaling might provide new opportunities for therapeutic intervention in ovarian cancer. Full article
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Open AccessReview
Plasma Biomarkers and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: New Tools for Better Patient Selection?
Cancers 2019, 11(9), 1269; https://doi.org/10.3390/cancers11091269 - 29 Aug 2019
Cited by 2
Abstract
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with non-small cell lung cancer (NSCLC). Although some patients can experience important response rates and improved survival, many others do not benefit from ICIs developing hyper-progressive disease or immune-related adverse events. This [...] Read more.
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with non-small cell lung cancer (NSCLC). Although some patients can experience important response rates and improved survival, many others do not benefit from ICIs developing hyper-progressive disease or immune-related adverse events. This underlines the need to select biomarkers for ICIs use in order to better select patients. There is currently no universally validated robust biomarker for daily use of ICIs. Programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB) are sometimes used but still have several limitations. Plasma biomarkers are a promising approach in ICI treatment. This review will describe the development of novel plasma biomarkers such as soluble proteins, circulating tumor DNA (ctDNA), blood TMB, and blood microbiome in NSCLC patients treated with ICIs and their potential use in predicting response and toxicity. Full article
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Open AccessArticle
Circulating Tumor Cell Enumeration and Characterization in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Cabazitaxel
Cancers 2019, 11(8), 1212; https://doi.org/10.3390/cancers11081212 - 20 Aug 2019
Abstract
(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles [...] Read more.
(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel. Full article
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Open AccessArticle
Kinome-Wide Screening with Small Interfering RNA Identified Polo-like Kinase 1 as a Key Regulator of Proliferation in Oral Cancer Cells
Cancers 2019, 11(8), 1117; https://doi.org/10.3390/cancers11081117 - 05 Aug 2019
Cited by 1
Abstract
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development [...] Read more.
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in various types of cancer. However, little is known about the role of kinases in OSCC cells. In this study, an arrayed kinome small interfering RNA (siRNA) library was used to screen oral cancer cell lines and counter assayed with normal fibroblast cells to identify the genes required for cancer cell proliferation. We found that polo-like kinase 1 (PLK1) was one of the most potent genes required for OSCC cell proliferation. The knockdown of PLK1 with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G2-M phase transition. Similar effects were observed in cells treated with the PLK1 kinase inhibitor BI6727. Besides, The Cancer Genome Atlas (TCGA) analysis revealed that PLK1 was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that PLK1 expression was highly correlated with the expression of its downstream effector, CCNB1, in patients with OSCC. Coexpression of the two genes resulted in a poor prognosis of OSCC patients, particularly those in the advanced stages of OSCC. Taken together, our results suggest that PLK1 might be a diagnostic or therapeutic marker for OSCC. Full article
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Open AccessBrief Report
Prognostic Role of Androgen Receptor in Triple Negative Breast Cancer: A Multi-Institutional Study
Cancers 2019, 11(7), 995; https://doi.org/10.3390/cancers11070995 - 17 Jul 2019
Abstract
Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis [...] Read more.
Background: The androgen receptor (AR) has emerged as a potential therapeutic target for AR-positive triple-negative breast cancer (TNBC). However, conflicting reports regarding AR’s prognostic role in TNBC are putting its usefulness in question. Some studies conclude that AR positivity indicates a good prognosis in TNBC, whereas others suggest the opposite, and some show that AR status has no significant bearing on the patients’ prognosis. Methods: We evaluated the prognostic value of AR in resected primary tumors from TNBC patients from six international cohorts {US (n = 420), UK (n = 239), Norway (n = 104), Ireland (n = 222), Nigeria (n = 180), and India (n = 242); total n = 1407}. All TNBC samples were stained with the same anti-AR antibody using the same immunohistochemistry protocol, and samples with ≥1% of AR-positive nuclei were deemed AR-positive TNBCs. Results: AR status shows population-specific patterns of association with patients’ overall survival after controlling for age, grade, population, and chemotherapy. We found AR-positive status to be a marker of good prognosis in US and Nigerian cohorts, a marker of poor prognosis in Norway, Ireland and Indian cohorts, and neutral in UK cohort. Conclusion: AR status, on its own, is not a reliable prognostic marker. More research to investigate molecular subtype composition among the different cohorts is warranted. Full article
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Open AccessArticle
Role of Bruton’s Tyrosine Kinase in Stage III Colorectal Cancer
Cancers 2019, 11(6), 880; https://doi.org/10.3390/cancers11060880 - 24 Jun 2019
Cited by 1
Abstract
Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective [...] Read more.
Background: Bruton’s tyrosine kinase (BTK) is involved in the immune response and its deficiency impairs B cell maturation. We evaluated the expression of a novel BTK isoform, p65BTK, in colorectal cancer (CRC), to identify its impact on survival. Materials and Methods: This retrospective study evaluated 87 consecutive stage III CRC patients treated at the National Cancer Institute of Aviano (1999–2017). Multiple specimens were collected and analyzed for staining intensity and percentage of tumor cells positive for p65BTK. Prognostic impact was tested by univariate Cox regression analysis. Results: After a median follow-up of 82.59 months, median disease-free survival (DFS) and overall survival (OS) were 11.67 months and 31.33 months, respectively. Interestingly, 10% of patients did not express p65BTK. For the immunohistochemistry IHC intensity 1, the best cutoff point was 1% of p65BTK positivity; for IHC intensity 2, it was 50%; and for IHC intensity 3, it was 80%. Through univariate analysis, patients with highly expressed p65BTK (IHC intensity 3 and ≥80%) were shown to have the worst prognosis in terms of DFS (HR: 6.23; p = 0.005; 95% C.I. 1.75–22.79) and OS (HR: 2.54; p = 0.025; 95% C.I. 1.12–5.76). Conclusions: p65BTK is frequently expressed in CRC and, if highly expressed, is an unfavourable prognostic factor. However, further confirmation is needed and its potential targeting needs to be studied. Full article
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Open AccessArticle
CHI3L1, NTRK2, 1p/19q and IDH Status Predicts Prognosis in Glioma
Cancers 2019, 11(4), 544; https://doi.org/10.3390/cancers11040544 - 15 Apr 2019
Cited by 1
Abstract
The aim of this study was to identify relevant biomarkers for the prognosis of glioma considering current molecular changes such as IDH mutation and 1p19q deletion. Gene expression profiling was performed using the TaqMan Low Density Array and hierarchical clustering using 96 selected [...] Read more.
The aim of this study was to identify relevant biomarkers for the prognosis of glioma considering current molecular changes such as IDH mutation and 1p19q deletion. Gene expression profiling was performed using the TaqMan Low Density Array and hierarchical clustering using 96 selected genes in 64 patients with newly diagnosed glioma. The expression dataset was validated on a large independent cohort from The Cancer Genome Atlas (TCGA) database. A differential expression panel of 26 genes discriminated two prognostic groups regardless of grade and molecular groups of tumors: Patients having a poor prognosis with a median overall survival (OS) of 23.0 ± 9.6 months (group A) and patients having a good prognosis with a median OS of 115.0 ± 6.6 months (group B) (p = 0.007). Hierarchical clustering of the glioma TCGA cohort supported the prognostic value of these 26 genes (p < 0.0001). Among these genes, CHI3L1 and NTRK2 were identified as factors that can be associated with IDH status and 1p/19q co-deletion to distinguish between prognostic groups of glioma from the TCGA cohort. Therefore, CHI3L1 associated with NTRK2 seemed to be able to provide new information on glioma prognosis. Full article
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Open AccessArticle
Automated Quantification of Extranuclear ERα Using Phosphor-Integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2 Breast Cancer
Cancers 2019, 11(4), 526; https://doi.org/10.3390/cancers11040526 - 12 Apr 2019
Abstract
In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure [...] Read more.
In addition to genomic signaling, Estrogen receptor alpha (ERα) is associated with cell proliferation and survival through extranuclear signaling contributing to endocrine therapy (ET) resistance. However, the relationship between extranuclear ERα and ET resistance has not been extensively studied. We sought to measure extranuclear ERα expression by immunohistochemistry using phosphor-integrated dots (IHC-PIDs) and to assess its predictive value for ET resistance. After quantitative detection of ERα by IHC-PIDs in vitro, we developed “the nearest-neighbor method” to calculate the extranuclear ERα. Furthermore, tissue sections from 65 patients with HR+/HER2- BC were examined by IHC-PIDs, and the total ERα, nuclear ERα, extranuclear ERα PIDs score, and ratio of extranuclear-to-nuclear ERα (ENR) were measured using the novel method. We demonstrate that quantification of ERα using IHC-PIDs exhibited strong correlations to real-time qRT-PCR (r2 = 0.94) and flow cytometry (r2 = 0.98). High ERα ENR was significantly associated with poor overall survival (p = 0.048) and disease-free survival (DFS) (p = 0.007). Multivariate analysis revealed that the ERα ENR was an independent prognostic factor for DFS [hazard ratio, 3.8; 95% CI, 1.4–11.8; p = 0.006]. Our automated measurement has high accuracy to localize and assess extranuclear ERα. A high ERα ENR in HR+/HER2 BC indicates decreased likelihood of benefiting from ET. Full article
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Open AccessReview
Diagnostic and Prognostic Potential of AKR1B10 in Human Hepatocellular Carcinoma
Cancers 2019, 11(4), 486; https://doi.org/10.3390/cancers11040486 - 05 Apr 2019
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although diagnostic measures and surgical interventions have improved in recent years, the five-year survival rate for patients with advanced HCC remains bleak—a reality that is largely attributable to an absence of early [...] Read more.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although diagnostic measures and surgical interventions have improved in recent years, the five-year survival rate for patients with advanced HCC remains bleak—a reality that is largely attributable to an absence of early stage symptoms, lack of adequate diagnostic and prognostic biomarkers, and the common occurrence of acquired resistance to chemotherapeutic agents during HCC treatment. A limited understanding of the molecular mechanisms underlying HCC pathogenesis also presents a challenge for the development of specific and efficacious pharmacological strategies to treat, halt, or prevent progression to advanced stages. Over the past decade, aldo-keto reductase family 1 member 10 (AKR1B10) has emerged as a potential biomarker for the diagnosis and prognosis of HCC, and experimental studies have demonstrated roles for this enzyme in biological pathways underlying the development and progression of HCC and acquired resistance to chemotherapeutic agents used in the treatment of HCC. Here we provide an overview of studies supporting the diagnostic and prognostic utility of AKR1B10, summarize the experimental evidence linking AKR1B10 with HCC and the induction of chemoresistance, and discuss the clinical value of AKR1B10 as a potential target for HCC-directed drug development. We conclude that AKR1B10-based therapies in the clinical management of specific HCC subtypes warrant further investigation. Full article
Open AccessArticle
A Simple and Highly Specific MassARRAY-Based Stool DNA Assay to Prioritize Follow-up Decisions in Fecal Immunochemical Test-Positive Individuals
Cancers 2019, 11(3), 423; https://doi.org/10.3390/cancers11030423 - 25 Mar 2019
Abstract
Background: Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection. [...] Read more.
Background: Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection. Methods: Twenty-one variants in five CRC-associated genes were selected for the sDNA panel. Cell line DNA and matched mutation-confirmed tissue and stool samples from 34 patients were used for accuracy assessment (cohort 1). The clinical performance of the sDNA assay was further evaluated in 101 independent FIT-positive stool samples (cohort 2). Results: In cohort 1, we obtained a 62% mutation concordance rate in paired tissue and stool samples of the CRC group, regardless of the FIT status. In cohort 2, 100% specificity in normal controls with positive FIT results was observed. By weighting the FIT value and the presence of a given variant type in stool and then summing the two scores, we found that a one-increment increase in the score was associated with a 4.538-fold risk (95% CI = 2.121–9.309) for malignancy in the FIT-positive setting. Conclusions: Our highly specific sDNA assay can help prioritize the most at-risk FIT-positive persons to receive prompt colonoscopic confirmation of CRC. Full article
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Open AccessReview
Circulating MicroRNA Biomarkers for Lung Cancer Detection in East Asian Populations
Cancers 2019, 11(3), 415; https://doi.org/10.3390/cancers11030415 - 23 Mar 2019
Cited by 2
Abstract
Background: Lung cancer (LC) is the leading cause of cancer-related death in Eastern Asia. The prognosis of LC highly depends on tumor stages and early detection could substantially reduce LC mortality. Accumulating evidence suggested that circulating miRNAs in plasma or serum may have [...] Read more.
Background: Lung cancer (LC) is the leading cause of cancer-related death in Eastern Asia. The prognosis of LC highly depends on tumor stages and early detection could substantially reduce LC mortality. Accumulating evidence suggested that circulating miRNAs in plasma or serum may have applications in early LC detection. We thus conducted a systematic literature review on the diagnostic value of miRNAs markers for LC in East Asian populations. Methods: PubMed and ISI Web of Knowledge were searched to retrieve relevant articles published up to 17 September 2018. Information on study design, population characteristics, investigated miRNAs and diagnostic accuracy (including sensitivity, specificity and area under the curve (AUC)) were independently extracted by two reviewers. Results: Overall, 46 studies that evaluated a total of 88 miRNA markers for LC diagnosis in East Asian populations were identified. Sixteen of the 46 studies have incorporated individual miRNA markers as panels (with 2–20 markers). Three promising miRNA panels with ≥90% sensitivity and ≥90% specificity were discovered, two of which were externally validated. Diagnostic performance of circulating miRNAs in East Asian populations was comparable to previously summarized performance in Western populations. Forty-four miRNAs were reported in both populations. No major differences in diagnostic performance by ethnicity of the same miRNA was observed. Conclusions: Circulating miRNAs or miRNA panels, possibly in combination with other promising molecular markers including epigenetic and genetic markers, may be promising candidates for noninvasive LC early detection. However, large studies with samples collected prospectively in true screening settings are required to validate the promising markers or marker panels. Full article
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Open AccessBrief Report
Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation
Cancers 2019, 11(3), 365; https://doi.org/10.3390/cancers11030365 - 15 Mar 2019
Abstract
Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective [...] Read more.
Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation. Full article
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Open AccessArticle
Association of miR-34a Expression with Quality of Life of Glioblastoma Patients: A Prospective Study
Cancers 2019, 11(3), 300; https://doi.org/10.3390/cancers11030300 - 04 Mar 2019
Cited by 1
Abstract
MiR-34a acts as tumor-suppressor by targeting many oncogenes related to proliferation, apoptosis, and invasion of gliomas. We studied the relationships between health-related quality of life (HRQOL), depression, and miR-34a expression status in patients with newly diagnosed glioblastoma (GBM). A comprehensive HRQOL assessment was [...] Read more.
MiR-34a acts as tumor-suppressor by targeting many oncogenes related to proliferation, apoptosis, and invasion of gliomas. We studied the relationships between health-related quality of life (HRQOL), depression, and miR-34a expression status in patients with newly diagnosed glioblastoma (GBM). A comprehensive HRQOL assessment was completed by 38 patients with glioblastoma prior to surgical resection and included the European Organization for Research and Treatment of Cancer (EORTC) questionnaire for cancer patients (QLQ-C30) and the Brain Cancer-Specific Quality of Life Questionnaire (QLQ-BN20), the Patient Health Questionnaire-9 (PHQ-9), the Karnofsky performance index (KPS), and The Glasgow Outcome Scale (GOS). The miR-34a expression in glioblastoma tissue was measured using quantitative reverse transcription PCR. Our findings show that lower miR-34a expression is significantly associated with higher tumor volume, worse physical functioning, lower KPS, and greater depressive symptom severity of GBM patients. Moreover, analysis reveals that miR-34a effects might be gender specific, as stronger relationships between miR-34a and patient functioning measures were observed in males when compared to females. Despite the fact that, due to small sample size, our results should be considered as preliminary, our study suggests that miR-34a is associated with tumor burden and can be important for health-related quality of life, functional status, and mood symptoms of glioblastoma patients. Full article
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