Tumor Biomarkers

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The complementary role of imaging and tumor biomarkers in gynecological cancers: an update of the literature

The complementary role of imaging and tumor biomarkers in gynecological cancers: an update of the literature

Gynecological tumors, including endometrial, cervical and ovarian cancer, have increased in incidence over time. The widespread introduction of screening programs and advances in diagnostic imaging methods has lead to a progressive increase in gynecological cancer detection. Accurate diagnosis and proper monitoring of disease remain the primary target for a successful treatment. In the last years, knowledge about cancer biomarkers has considerably increased providing great opportunities for improving cancer detection and treatment. In addition, in the last few years there has been an important development of imaging techniques. Nowadays, a multimodal approach including the evaluation of serum tumor biomarkers combined with imaging techniques, seems to be the best strategy for assessing tumor presence, spread, recurrence, and/or the response to treatment in female cancer patients In this review we provide an overview of the application of biomarkers combined with novel imaging methods and highlight their roles in female cancer diagnosis and follow-up.
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Original Article Relationship between EGFR gene mutation and serum tumor biomarkers in advanced lung adenocarcinoma

Original Article Relationship between EGFR gene mutation and serum tumor biomarkers in advanced lung adenocarcinoma

Serum tumor biomarkers have the advantage of convenient detection that can help diagno- sis. Studies had found that serum CEA level was associated with EGFR mutation rate in NSCLC patients [8, 9]. In addition, serum CEA and CA242 were also associated with EGFR mutation in lung adenocarcinoma patients [10, 11], suggesting that serum tumor marker can be used to evaluate EGFR mutations potential- ly. At present, related studies all focused on tumor marker CEA while the other serum bio- markers were still lack of research. Thus, we selected CA125, CA199, and CYFRA211 as the research target. Studies revealed that EGFR gene mutation rate was high in lung adenocar- cinoma patients [12]. For advanced lung ade- nocarcinoma patients unable to undergo sur- gery treatment, targeted drugs was mainly used in these patients. Currently, there were still lack of report about the relationship between EGFR gene mutation and serum tumor markers in advanced lung adenocarcinoma patients. Through detecting EGFR mutation and serum CEA, CA125, CA199 and CYFRA211 levels, we aimed to evaluate the correlation between tumor markers and EGFR mutation. It may provide simple method to predict EGFR mutation, and searching potential feasible index for targeted therapy judgment.
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Dysbiosis of the Gut Microbiome is associated with Tumor Biomarkers in Lung Cancer

Dysbiosis of the Gut Microbiome is associated with Tumor Biomarkers in Lung Cancer

Lung cancer is a malignancy with high morbidity and mortality worldwide. More evidences indicated that gut microbiome plays an important role in the carcinogenesis and progression of cancers by metabolism, inflammation and immune response. However, the study about the characterizations of gut microbiome in lung cancer is limited. In this study, the fecal samples were collected from 16 healthy individuals and 30 lung cancer patients who were divided into 3 groups based on different tumor biomarkers (cytokeratin 19 fragment, neuron specific enolase and carcinoembryonic antigen, respectively) and were analyzed using 16S rRNA gene amplicon sequencing. Each lung cancer group has characterized gut microbial community and presents an elimination, low-density, and loss of bacterial diversity microbial ecosystem compared to that of the healthy control. The microbiome structures in family and genera levels are more complex and significantly varied from each group presenting more different and special pathogen microbiome such as Enterobacteriaceae, Streptococcus, Prevotella, etc and fewer probiotic genera including Blautia, Coprococcus, Bifidobacterium and Lachnospiraceae. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and COG annotation demonstrated decreased abundance of some dominant metabolism-related pathways in the lung cancer. This study explores for the first time the features of gut microbiome in lung cancer patients and may provide new insight into the pathogenesis of lung cancer system, with the implication that gut microbiota may serve as a microbial marker and contribute to the derived metabolites, development and differentiation in lung cancer system.
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Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ

Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ

harmless. Because no reliable diagnostic tests or imaging techniques are able to distinguish between a benign and a malignant cyst, approximately seven patients with benign lesions are operated for every ovarian cancer found [4]. Im- proving early diagnosis can help avoid unnecessary opera- tions. Using CA-125 as a biomarker for early detection has been thoroughly investigated in several studies [5-8]. How- ever, CA-125 is often falsely negative in fertile women with EOC and in early stage EOC and CA-125 is positive in a variety of benign diseases and therefore not sensitive enough to be used for general screening [9-12]. Among hundreds of suggested new biomarkers, human epididymis protein 4 (HE4) is a strong candidate for detection of EOC [13,14]. Reports indicate that HE4 and CA-125 in serum samples detect ovarian cancer equally, while HE4 has a better capacity to distinguish benign disease in fertile women from those with malignant tumors. Studies also
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Impact of tumor biomarkers and patient’s age on the “disease stage” in women with breast cancer in Erbil city

Impact of tumor biomarkers and patient’s age on the “disease stage” in women with breast cancer in Erbil city

on Cancer (AJCC) TNM staging system as follows: 11 Stage I (early stage): the primary breast tumor is no larger than two cm in greatest diameter, and has not spread to the regional lymph nodes. Stage II and III (early and late locally advanced): the primary breast tumor is more than two cm in size, and/or may have spread to the regional lymph nodes. Stage IV (metastatic): the primary breast tumor have spread to other distant organs and sites of the body such as lungs, bones, liver, brain…etc Based on the tumor biomarker status, patient cases were classified as hormone receptor-positive if either the estrogen receptor (ER) marker or the progesterone receptor (PR) was positive,
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Ovarian cyst fluid is a rich proteome resource for detection of new tumor biomarkers

Ovarian cyst fluid is a rich proteome resource for detection of new tumor biomarkers

of only 20 abundant proteins i.e. albumin, immunoglo- bulins, transferrin and macroglobulins [18]. By using ovarian cystic fluid we made the assumption that we would increase the chance for detection of rare, more tumor-specific proteins. However, there seem to be a high resemblance between ovarian cyst fluid and the serum proteome since the abundant large proteins were the most prominent ones also in the present study. Simi- lar resemblances between serum and fluids from other compartments such as pancreatic cysts, ascites and breast duct fluids have also been described [8,11,12]. Use of careful and selective depletion of high abundance pro- teins from the ovarian cyst fluid might increase access to other specific biomarkers. One major limitation with the method used in the present study is the lack of exact protein identification of the mass-peaks. Fortunately the abundant peaks observed as differentially expressed be- tween benign and malignant ovarian cystic fluid, have been purified and confidently identified in several earlier studies [19-27]. Especially the peaks for ApoC-I and TTR have been correctly identified after several different
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Original Article CEA, CA125, CA153 and TSGF act as diagnostic tumor biomarkers for patients with rectal carcinoma

Original Article CEA, CA125, CA153 and TSGF act as diagnostic tumor biomarkers for patients with rectal carcinoma

article detected CEA, CA153, TSGF and CA125. Their sensitivities were 28.7%, 24.8%, 44.7% and 32.4% respectively. The sensitivity of com- bined detection sensitivity was 85.7%. The accuracy of joint detection was 82.6%, which was better than the single detection of tumor markers. CEA is a glycoprotein. It appeared the endothelial cells of fetal gastrointestinal tract of 3 to 6 months infant and gradually disap- peared with fetal growth. When the body had a tumor, CEA will reappear. CEA is commonly used in the diagnosis of gastrointestinal cancer [8, 9]. The levels of CEA in patients with article gastric cancer, rectal cancer, duodenal cancer, colon cancer were higher than patients with benign gastrointestinal diseases. The single detection of CEA levels showed high false posi- tive, low sensitivity and accuracy in the diagno- sis malignancy tumors. The article the sensitiv- ity and accuracy of CEA were 28.7%, 53.7%. Some article showed that the patients with pneumonia, smokers, gastrointestinal inflam- mation had the high levels of CEA.
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Optimizing fresh specimen staining for rapid identification of tumor biomarkers during surgery

Optimizing fresh specimen staining for rapid identification of tumor biomarkers during surgery

In summary, the selected DDSI staining technique showed significant improvement in distinguishing tumor from normal adipose tissue in excised specimens over targeted staining alone. Perturbations in antibody-fluorophore probe pairs had little effect on DDSI performance with consistent tumor vs. normal tissue diagnostic performance across all tested staining conditions. Using antibody based probes and visible fluorophores, the probe penetration and imaging depth are inherently surface weighted and likely limited to a few microns at best. However, according to new consensus criteria for breast cancer margin status, margins are considered to be negative for tumor when there is no tumor at the “ink” or surface of the resected specimen, making the current probe composition viable for clinical translation [57]. DDSI was also demonstrated to be an accurate reporter of tumor specific molecular expression levels of HER2, and provided a validated diagnostic method for intraoperative tumor margin detection with high sensitivity and specificity for BCS. The DDSI framework is generalizable to surgical resection of other cancers, and we are actively studying its application for other indications. With further development and application to a range of cancer biomarkers, this technique could provide the ability to identify diverse cancer phenotypes for improved tumor margin assessment intraoperatively, reducing re-excision rates and improving patient outcomes.
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Investigation of Combining Serum Tumor Biomarkers and Clinical Features for Elderly Lung Cancer Diagnosis and Classification

Investigation of Combining Serum Tumor Biomarkers and Clinical Features for Elderly Lung Cancer Diagnosis and Classification

thological diagnosis, nor the use of two obvious clinical indicators and serological markers, the answer is lung problems are valuable only to a certain extent. Patients age defined in the obvious, smoking status can be easily obtained through interrogation serological CEA, NSE de- termination of minimally invasive and easy to carry out, the burden of the patient’s medical economics is limited, and these are used to the advantage of the diagnostic mo- del. Further after carrying out the diagnosis of lung can- cer, the discriminant model is composed of four indica- tors above. The various indicators linear discriminant coefficient is the difference in the effectiveness of identi- fication of lung adenocarcinoma, squamous and SCLC the ability of the three main types of lung cancer, the discriminant function correctly points 54.9% of patients with lung cancer type and after a randomized cross-va- lidation of the equation can also be obtained 52.4% cor- rect discrimination. As clinicians, the physical presence of a patient is essential to confirm the diagnosis, the use of simple and effective way to get a satisfactory result for clinical expectations; the combination clinical features of the tumor serum markers discriminant equation can to some extent, be part of the answer to this problem. The past clinical empirical judgment by mathematical me- thods to quantify a rigorous scientific process of logical operations, thereby reduced the error of empirical judg- ment; and, after clinical validation of large sample, the diagnostic model can be used as auxiliary automatic di- agnosis system for large-scale population screening has a significant advantage compared to the lower dose spiral CT, chest X-rays and other tests etc. It’s simple, econo- mic, and fewer adverse reactions, easy to equip and scale for the acceptance of small medical institutions where other screening tests could not be substituted.
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MicroRNAs, long noncoding RNAs, and circular RNAs: potential tumor biomarkers and targets for colorectal cancer

MicroRNAs, long noncoding RNAs, and circular RNAs: potential tumor biomarkers and targets for colorectal cancer

mote CRC cell proliferation and invasion via other multiple mechanisms. For example, the EMT plays important roles in tumor metastasis. For example, miR-19a is upregulated in CRC tissues, and high expression of miR-19a is signifi- cantly associated with lymph node metastasis. Interestingly, miR-19a is upregulated by TNF- α and is required for TNF- α -induced EMT and metastasis in CRC cells. 44

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<p>Investigation Of Small Molecular Substances As Potential Biomarkers For Discrimination Of Gastric Tumor</p>

<p>Investigation Of Small Molecular Substances As Potential Biomarkers For Discrimination Of Gastric Tumor</p>

MS might be a new alternative to the standard frozen- section histology method. An important advantage of MS analysis is the objective capture of tissue bioinformatics. Many studies using mass spectrometry to identify biomar- kers for the diagnosis of GT have been reported. Chang et al observed that human neutrophil peptides 1 – 3, which are considered to be potential biomarkers for the diagnosis and surveillance of gastric cancer, were overexpressed in gastric cancerous tissues using MALDI-TOF MS. 19 Wang et al reported that fatty acid binding protein (FABP1) and fatty acid synthase (FASN) might be biomarkers for the detection of early gastric cancer. 8 Furthermore, Kim et al showed that vitronectin, clusterin isoform 1, thrombospon- din 1, and tyrosine-protein kinase SRMS could discrimi- nate gastric cancer serum from the control. 20
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Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond

Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond

Ultimately, a single biomarker may not adequately predict response to PD-1 immune checkpoint therapies, and a combination of factors may need to be taken into account to predict responses. Based on the level of CD8A and PD-L1 expression, Ock et al. described four distinct tumor microenvironment immune types (TMIT) [62]. Tumors with an elevated CD8A and PD-L1 expres- sion were grouped as Type I TMIT. Type I TMIT tumors had a significantly higher mutational burden compared with the other types of tumors, higher number of neoantigens, and were also associated with PD-L1 amplification, all characteristics which imply responsiveness to PD-1 and PD-L1 inhibition. This suggests that TMIT may be a more comprehensive score as a predictive biomarker for these CPIs. Prospective clinical trials using the TMIT framework are necessary. These types of composite assessments which combine multiple biomarkers within the same platform are currently in development. A concern about using composite biomarker panels, however, is both their clinical utility (will it be feasible to wait for multiple assays to return before starting CPI therapy?) as well as increased costs associated with multi-omic and IHC profiling.
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pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in human tumor cells

pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in human tumor cells

by the Heavy Ion Research Facility in Lanzhou (HIRFL) at the Institute of Modern Physics, Chinese Academy of Sci- ences (IMP–CAS). Since the energy decays through the vacuum window, air gap, Petri dish cover and medium, the energy of the ion beams on cell samples was adjusted to be 300 meV/u, corresponding to a LET of 15 keV/μm and the dose rate was adjusted to be about 0.4 Gy/min. The ion beams were calibrated using an absolute ioniza- tion chamber. The tumor cells were irradiated by plateau of carbon ions LET curve and the dose of scatter off the walls of the plate has been calculated and incorporated into the total dose. The data (preset numbers converted to absorbed dose of particle radiation) was automatically obtained using a microcomputer during irradiation. The dose rate was approximately 1.38  Gy/min and the dose used for 12 C 6+ irradiation was 0.5, 1, 2 and 4 Gy.
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New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer

Various modalities have been studied and proposed to assess and predict responses to CRT. For morphologic assessment of tumor response after preoperative CRT, endoscopic findings and imaging studies, including magnetic resonance imaging (MRI) and positron emission tomography (PET), have been used and demonstrate good results. Clinical factors and se- rum carcinoembryonic antigen (CEA) have also been investi- gated and shown to hold some predictive value. Notwithstand- ing, due to the limitations of these modalities, molecular bio- markers analyzed using immunohistochemistry (IHC) and gene expression profiling have been investigated and may play a possible role as predictive models for tailored treatment of pa- tients undergoing preoperative CRT.
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Imaging Key Biomarkers of Tumor Angiogenesis

Imaging Key Biomarkers of Tumor Angiogenesis

treatment regimens. For example, regression might involve so-called “normalization” of tumor vascula- ture (106, 107), which might provide for a better de- livery of chemotherapeutic drugs to tumor growth areas. In turn, revascularization might also provide for better drug delivery, justifying the combination regimens and particularly metronomic combinations (108). On the other hand, recent research in mouse tumor models suggested that revascularization might stimulate invasiveness and metastatic dissemination of primary tumor (105, 109). In view of these com- plexities, there is an urgent and still unmet need in developing predictive biomarkers suitable for analy- sis of different stages in the course of VEGF/VEGFR-directed therapies (110). Since vascu- lar regression and rebound are associated with the complex dynamic changes in the prevalence of the drug target itself, it is tempting to speculate that non-invasive molecular imaging of VEGF receptors would be able to satisfy this need. If responses of human vasculature follow the same pattern of vascu- lar regression and rebound, longitudinal VEGFR im- aging could be able to detect patients who respond to therapy at the early stage of treatment and then iden- tify those patients whose VEGFR-2 expressing vascu- lature stop responding and who would benefit if treatment is changed.
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Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers

Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers

Abstract: Neoadjuvant therapy (NAT) has been used increasingly in patients with locally advanced or early-stage breast cancer. However, the accurate evaluation and prediction of response to NAT remain the great challenge. Biomarkers could prove useful to identify responders or nonresponders, or even to distinguish between early and delayed responses. These biomarkers could include markers from the tumor itself, such as versatile proteins, genes, and ribonucleic acids, various biological factors or peripheral blood cells, and clinical and pathological features. Possible predictive markers could also include multiple features from functional imaging, such as standard uptake values in positron emission tomography, apparent diffusion coefficient in magnetic resonance, or radiomics imaging biomarkers. In addition, cells that indirectly present the immune status of tumor cells and/or their host could also potentially be used as biomarkers, eg, tumor-infiltrating lymphocytes, tumor-associated macrophages, and myeloid-derived sup- pressor cells. Though numerous biomarkers have been widely investigated, only estrogen and/ or progesterone receptors and human epidermal growth factor receptor have been proven to be reliable biomarkers to predict the response to NAT. They are the only biomarkers recommended in several international guidelines. The other aforementioned biomarkers warrant further valida- tion studies. Some multigene profiling assays that are commercially available, eg, Oncotype DX and MammaPrint, should be used with caution when extrapolated to NAT settings. A panel of combined multilevel biomarkers might be able to predict the response to NAT more robustly than individual biomarkers. To establish such a panel and its prediction model, reliable methods and extensive clinical validation are warranted.
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Evaluating blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers

Evaluating blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers

We found that despite the reported utility of NSE and ChrA blood levels as biomarkers for low grade NETs, clinical use of NSE and ChrA levels in MCC patients failed to correlate with outcomes, disease progression, or tumor burden. In the same patient population we found that maintrac detection readily identified EpCAM+ CTC with high sensitivity. Moreover, adding CD56 as a second tumor marker increased the specificity of CTC detection. Although CTC counts reflected tumor burden, additional follow up is needed to determine how CTC correlate with disease outcomes. The use of CTC as biomarkers for MCC will require further development and validation, but our results and those of Blom et al. suggest CTC may be useful in the staging and longitudinal monitoring of MCC.
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Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

The prognostic role of tumor MET has been previously published, with patients on placebo surviving 3.8 months if MET-High, and 9.0 months if MET-Low [8]. In the current analysis, we observed a dramatic difference in MET status between biopsies taken before and after sorafenib treatment. This is in line with literature suggesting that high MET expression correlates with hypoxia, resistance to anti-angiogenic therapies, and poor prognosis in HCC [10-12, 35], and further supports the prognostic role of MET. A correlation between MET status and transarterial chemoembolization (TACE), which also causes hypoxia, could not be assessed due to the small number of TACE-treated patients in this study (Table 2). Our results, confirmed by data from the larger METIV- HCC study, suggest that biopsies taken after sorafenib can more reliably assess the prognostic status of MET in second-line HCC patients [36]. Moreover, the weight of MET-Low as a positive prognostic factor may have been underestimated in the ARQ 197-215 study because MET staining was largely assessed on pre-sorafenib samples. This also emphasizes the need to biopsy HCC patients following sorafenib treatment in order to succeed in biomarker research, and to cautiously consider therapeutic options based on life expectancy.
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Original Article MiR-21-3p and miR-21-5p in tumor tissue as diagnostic biomarkers for gastric cancer

Original Article MiR-21-3p and miR-21-5p in tumor tissue as diagnostic biomarkers for gastric cancer

Abstract: Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs, which modulate the expres- sion of certain target genes and thereby control multiple biological processes. In this study, we selected miR-21- 3pand miR-21-5pto evaluate their diagnostic value for Gastric Cancer (GC). Methods: A total of 50 GC patients were recruited. Normal gastric, paracancerous, and GC tissues were collected from all these participants during the operation. The levels of miR-21-3p and miR-21-5p were determined by quantitative real-time PCR (qPCR) with U6snRNA expression used as the internal control. Nonparametric tests were employed for the further statistical analyses, where relative expression of miR-21-3p or miR-21-5p in tumor or paracancerous tissues to that in normal tissues were employed to rule out the individual difference. Results: Higher expression of both miR-21-3p and miR- 21-5pwere identified in GC tissue than in paracancerous tissue. Significant differences of miR-21-3p or miR-21-5p level were detected among groups subdivided by depth of tumor invasion, lymph node metastasis and clinical tumor node metastasis (TNM) stage. But when it came to tumor differentiation, the difference of miR-21-3p was not sta- tistically significant, while miR-21-5p was. Both of them showed moderate diagnostic value (miR-21-3p: AUC=0.710, sensitivity =82%, specificity =64%; miR-21-5p: AUC =0.726, sensitivity =82%, specificity =66%). Conclusion: Both miR-21-3p and miR-21-5p may serve as potential biomarker for GC diagnosis, while miR-21-5p is more potent in distinguishing the differentiation of the tumor.
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Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers : companion diagnostics for personalized medicine

Mitochondrial biomarkers predict tumor progression and poor overall survival in gastric cancers : companion diagnostics for personalized medicine

Unfortunately, the 5-year survival rates for gastric cancer patients vary widely, from as low as 15% to as high as 60%. As such, more effective biomarkers are urgently needed for the early stratification of gastric cancer patients, into low-risk and high-risk groups at diagnosis. Here, we directly tested the hypothesis that markers of mitochondrial biogenesis and respiratory function may have significant prognostic value in the early identification of high-risk gastric cancer patients, with increased tumor progression and poor overall survival.

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