Single Prognostic Marker Research Articles

Prognostic Value of B-Type Natriuretic Peptide in Hospitalized Patients with Pneumonia

Background: Pneumonia is a major medical problem and is foremost infectious cause of death in developed countries. A rapid and reliable predictor might aid physicians in identifying hospitalization, intensive care unit admission, and treatment changes. B-type natriuretic peptide (BNP) has consistently been observed to improve the diagnosis and management of hospitalized patients with pneumonia. This investigation aimed to study the importance of BNP in the assessment of severity of pneumonia in a tertiary care center in South India. Subjects and Methods: A hospital-based observational research was carried out on patients admitted during the period of September 2016 to July 2018 with sample size of 108. All patients satisfying the inclusion criteria were enrolled. Detailed clinical history and physical examination findings were noted. Diagnostic criteria symptoms were recorded following the standard protocol. BNP was measured using the double-antibody sandwich enzyme-linked immunosorbent assay. The statistical analyses were done using the statistical software R version 3.6.3 and MS Excel. Results: Out of 108 patients, 48 (44.44%) were female and 60 (55.56%) were male. Of these, 45 (41.67%) patients identified with community-acquired pneumonia, 27 (25%) with health-care-associated pneumonia, 26 (24.07%) with aspiration pneumonia, and 10 (9.26%) with pneumonia with comorbid conditions. BNP levels among survivors and nonsurvivors were 193.52 ± 124.93 and 413.08 ± 149.38 pg/ml, respectively. The total mortality was 13/108 (12.04%). Out of 13 patients, 12 (92.31%) nonsurvivors had BNP level ≥200 pg/ml and 1 (7.69%) had 100–200 pg/ml. Conclusion: BNP levels could be a useful single prognostic marker for pneumonia. BNP levels correlated with the clinical severity of pneumonia.

Prognostic impact of tumor microenvironment-related markers in patients with adenocarcinoma of the lung

Cancer-associated fibroblasts (CAFs) are a prominent component in the tumor microenvironment (TME), which plays an important role in lung carcinogenesis. Here, we investigated microenvironmental markers expressed by CAFs, including α-smooth muscle actin, CD10, podoplanin, fibroblast-specific protein 1, platelet-derived growth factor α and β, fibroblast-associated protein, tenascin-C, zinc finger E-box binding homeobox 1 (ZEB1), and twist-related protein 1 expression levels. We evaluated samples from 257 patients with lung adenocarcinoma (LAD) to assess the associations of CAF-related protein expression patterns with prognosis. LAD cases were stratified using cluster analysis. To determine the utility of prognostic markers in LAD, univariate and multivariate analyses were performed. LAD cases were classified into subgroups 1 and 2. Subgroup 2 was shown to be significantly correlated with disease-free and overall survival using univariate and multivariate analyses in this group. Upregulation of podoplanin was identified as a single prognostic marker in this study by univariate and multivariate analyses. In addition, ZEB1 overexpression was correlated with disease-free survival. Our current results suggested that the specific CAF phenotype (e.g., the expression pattern of CAF-related proteins) could predict outcomes in patients with LAD. In addition, podoplanin upregulation may predict outcomes in these patients.

Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II and III Colorectal Cancer: Novel Tumor Prognostic Markers.

BackgroundBiological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression.MethodsImmunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts.ResultsStage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses.ConclusionsWe suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.

Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study

BackgroundTo evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP®.MethodsSerum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality.ResultsVA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67–0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality.ConclusionsSerum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer.

We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren's intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.

Prognostic value of soluble major histocompatibility complex class I polypeptide-related sequence A in non-small-cell lung cancer – significance and development

Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) is a useful marker in surveillance of lung cancer. High serum sMICA level in patients with non-small-cell lung cancer (NSCLC) seems to be a poor prognostic factor being correlated with poor differentiation and advanced stage. However, the low specificity limits its role as a single prognostic marker of NSCLC, but its evaluation, in addition to standard serum markers, could improve the staging of NSCLC. Despite promising, all current studies are insufficient to assess the real efficiency of sMICA as a prognostic marker of NSCLC, and hence, future studies are required to validate it.

Correlating Ki67 and other prognostic markers with Oncotype DX recurrence score in early estrogen receptor-positive breast cancer.

Decisions regarding adjuvant chemotherapy for early breast cancer are complex. Ki67 is increasingly used, in conjunction with conventional prognostic markers, to help decide the use of adjuvant chemotherapy for early breast cancer. Ki67 has been proposed as an economical alternative to Oncotype DX recurrence score (RS), which is a validated prognostic marker for disease recurrence and predictive marker for benefit from chemotherapy. This study aimed to determine in patients where conventional prognostic markers did not provide a clear recommendation for adjuvant chemotherapy, whether Ki67 could be a substitute for RS. We reviewed all cases of luminal-type node-negative early breast cancer (T1-2, N0-1mi, M0, estrogen receptor positive, HER2 negative) referred for Oncotype DX testing by the multidisciplinary team at an Australian tertiary private hospital from 14th December 2006 to 31st December 2013, when conventional prognostic markers did not provide a clear recommendation for adjuvant chemotherapy. RS was correlated with Ki67, along with other conventional prognostic markers including tumor size, grade, mitotic rate and lymphovascular invasion. Spearman's rank order correlation coefficient and Pearson product-moment correlation coefficient (r) were used for ordinal and continuous variables, respectively. A total of 58 patients were analyzed, median Ki67 was 15% (range 2-50%) and the median RS was 16 (range 3-65). There was no positive correlation between Ki67 and RS (r=0.01, P=0.93). No single conventional prognostic marker was shown to significantly correlate with RS, including tumor size (r=-0.02, P=0.88), grade (r=0.10, P=0.44), mitotic rate (r=-0.07, P=0.69) and lymphovascular invasion (r=-0.12, P=0.39). Ki67 and conventional prognostic markers do not correlate with Oncotype DX RS. In the setting where conventional prognostic markers do not show a clear indication for or against adjuvant chemotherapy as determined by consensus in a multidisciplinary team, Ki67 is not a substitute for Oncotype DX testing. RS may provide additional information to aid decision making for adjuvant chemotherapy.

Validation of a B-type natriuretic peptide as a prognostic marker in pneumonia patients: a prospective cohort study

ObjectivesTo validate a B-type natriuretic peptide (BNP) as a prognostic marker in pneumonia patients.DesignA prospective cohort study.SettingKanazawa Medical University Himi Municipal (a 250-bed community hospital in Himi-shi, Toyama-ken, Japan).ParticipantsAll patients...

Long-term effects of deep brain stimulation for movement disorders: a literature-based analysis

Deep brain stimulation has become an established therapy for various movement disorders but questions regarding its long-term effectiveness remain. This study was designed to evaluate the long-term effectiveness of deep brain stimulation for movement disorders refractory to current medical therapy based on published long-term studies. A review was carried out of all available studies with a minimum follow-up of 5 years of patients with deep brain stimulation for Parkinson's disease, essential tremor and dystonia. A total of 23 studies of deep brain stimulation for Parkinson's disease, 7 studies for essential tremor and 14 studies for dystonia were included. After a follow-up of at least 5 years, improvement of current motor scores could be observed in Parkinson's disease (subthalamic stimulation) by approximately 40%, by approximately 50% for essential tremor and by 60% for dystonia (mostly generalized forms). In Parkinson's disease, motor improvements tend to diminish over time due to progression of dysarthria, axial symptoms and other motor features less responsive to deep brain stimulation. Non-dopaminergic symptoms tend to progress and lessen the positive effects on the quality of life. There appears to be a subgroup of patients with essential tremor who show decreasing effectiveness of deep brain stimulation, probably related to disease progression. Currently, no single prognostic marker has been established to identify this subgroup. Most forms of secondary dystonia seem to respond more variably than primary generalized dystonia. Deep brain stimulation remains a relatively safe and effective therapy in carefully selected patients after long-term follow-up according to published data, although disease progression and other disease-specific factors seem to modify its effectiveness over time.

Is Above Age 45 Appropriate for Upstaging Well-Differentiated Papillary Thyroid Cancer?

ObjectiveAge greater than 45 years old is a prognostic marker in well-differentiated papillary thyroid cancer (PTC) using the American Joint Cancer Committee/Union Internationale Contre le Cancer Tumor Nodes Metastasis (AJCC/UICC TNM) staging system. Our clinical observation has been that patients aged 45 to 64 years have similar outcomes when compared to patients younger than 45 years, and we questioned the origin and accuracy of this prognostic variable. MethodsUsing SEERstat software, we analyzed the Surveillance, Epidemiology, and End Result (SEER) database for PTC using the following International Classification of Diseases for Oncology (ICD-O) codes: 8050, 8260, 8340, 8341, 8342, 8243, and 8344. Data were stratified in 5-year categories by age at diagnosis from 20 to 84 years old, with patients 85 years old and above categorized together. Survival is reported as cause specific. ResultsA total of 53,581 patients were identified. The 5-year survival rate decreased with each increasing age category with no inflection point at age 45 in the survival curve. While the prognosis was less favorable in each advancing age group, survival remained above 90% for all age groups under 65 years. ConclusionA review of the literature reveals a lack of data supporting the use of age 45 as a prognostic variable. Our SEER database review revealed a continuum of disease-specific mortality for each incremental 5-year time period above age 45. We conclude that the current use of age 45 as a single prognostic age marker does not accurately reflect the progressive mortality risk that is apparent with each 5-year increment in age. (Endocr Pract. 2013; 19:995-997)

肝予備能良好な肝細胞癌に対する肝動脈塞栓術の予後予測からみた治療切り替え時期の検討

Criteria for switching from transcatheter arterial chemo-embolization (TACE) to sorafenib or other chemotherapy in patients with hepatocellular carcinoma (HCC) resistant to repeated TACE have not been established. Herein, we propose an easy to implement method for such determination. One hundred six patients with advanced HCC (beyond Milan criteria) without venous invasion by the tumor or extra-hepatic metastasis and with good liver function (Child-Pugh A class) who were treated by repeated TACE from 2000 to 2011 were analyzed. We combined the scores for the tumor markers alpha-fetoprotein (AFP, ≥100 ng/mL), fucosylated AFP (AFP-L3, ≥10%), and protein induced by vitamin K absence-II (PIVKA-II, ≥100 mAU/mL) into a single prognostic marker, then added up the positive factors in each case. In patients with a score under 2, TACE could control HCC. When HCC is not controlled by TACE after the patient has a score of 2 or more points, switching to the next therapy should be considered.

Histamine Blood Concentration in Ischemic Heart Disease Patients

The aim of this study was to investigate histamine blood concentration in subjects suffering from different types of ischemic heart diseases during the period of eight days. Our results showed that the histamine blood level was associated with different types of ischemic heart diseases. The blood histamine level in all investigated patients was significantly higher when compared to control subjects (44.87 ± 1.09 ng mL−1), indicating the increase of histamine release in patients suffering from coronary diseases. In patients suffering from ACS-UA and ACS-STEMI, the second day peak of histamine level occurs (90.85 ± 6.34 ng mL−1 and 121.7 ± 6.34 ng mL−1, resp.) probably as the reperfusion event. Furthermore, our data suggest that histamine can be additional parameter of myocardial ischemia along with cardiac specific enzymes and may prove to be an excellent single prognostic marker for multitude of ischemic heart diseases.

Value of the different prognostic systems and biological markers for predicting severity and progression of acute pancreatitis

Objective. Several tools have been developed for severity stratification in acute pancreatitis (AP). They include single biochemical markers and complex scoring systems, all of which aim at an early detection of severe AP to optimize monitoring and treatment of these patients. The aim of this study was to reassess and compare the value of some known and newly-introduced prognostic markers in the clinical context. Material and Methods. We have conducted a prospective observational study. One hundred and eight patients with a diagnosis of AP and onset of the disease within last 72 h were included in this study. Clinical data and expression results of some serum biochemical markers were used for statistical analysis. The diagnostic performance of scores predicting severity and progression of AP, cut-off values, specificity, and sensitivity were established using receiver operating characteristic curve analysis. Results. Among single biochemical markers, C-reactive protein remains the most useful. Despite its delayed increase, it is accurate, cheap, and widely available. Interleukin-6 and macrophage migration inhibitory factor seem to be new promising parameters for use in clinical routine. Pancreas specific scores (Imrie-Glasgow, pancreatitis outcome prediction) and scores assessing organ dysfunction (acute physiology and chronic health evaluation II, multiple organ dysfunction score, and Marshall score) remain of value in determining the severity, complications, and possible outcome of AP. Conclusions. Indication, timing, and consequences of the methods applied need to be carefully considered and incorporated into clinical assessments. Currently, there is no single prognostic marker that would cover the whole range of problems associated with the treatment of AP. The prediction of severity and progression of AP can be achieved using a series of accurate methods. The decision to undertake interventional or surgical treatment is the most complex task requiring both clinical judgment and meticulous monitoring of the patient.

Low expression of CysLT 1R and high expression of CysLT 2R mediate good prognosis in colorectal cancer

Colorectal cancer is the third most common cancer type in the Western world. In search of new treatment possibilities, the inflammation mediators, know as cysteinyl leukotrienes (CysLTs), have been shown to regulate intestinal epithelial cell survival and proliferation via the CysLT 1R, and cell differentiation via the CysLT 2R. These results prompted us to investigate the significance of CysLT 1R and CysLT 2R expression in colorectal cancer tissue for patient survival. The CysLT 1R, CysLT 2R, β-catenin and Bcl-xL protein expression levels were evaluated by immunohistochemistry in a tissue microarray of 329 colorectal patients. We found that high nuclear expression of CysLT 1R is associated with a poor prognosis, whereas high nuclear expression of CysLT 2R is associated with a good prognosis. We also observed that patients with colorectal tumours characterised by high CysLT 1R but low CysLT 2R nuclear expression had the lowest survival expectancy, whereas patients with colorectal tumours characterised by low CysLT 1R but high CysLT 2R nuclear expression had the best survival expectancy. Interestingly, β-catenin as a single prognostic marker did not exhibit any prognostic value. However, in patients with tumours characterised by a high CysLT 1R nuclear expression, an elevated β-catenin nuclear expression had a significantly prognostic value. In conclusion these data indicate that nuclear expressions of CysLTRs are potential prognostic indicators of colorectal cancer.

Quantitative multiplexed analysis of ErbB family coexpression for primary breast cancer prognosis in a large retrospective cohort

Assessment of outcome using a single prognostic or predictive marker is the current basis of targeted therapy, but is inherently limited by its simplicity. Multiplexing has provided better classification, but has only been done quantitatively using RNA or DNA. Automated quantitative analysis is a new technology that allows quantitative in situ assessment of protein expression. The authors hypothesized that multiplexed quantitative measurement of ErbB receptor family proteins may allow better prediction of outcome. The authors quantitatively assessed the expression of 6 proteins in 4 subcellular compartments in 676 patients using breast carcinoma tissue microarrays. Then using Cox proportional hazards modeling and unsupervised hierarchical clustering, they assessed the prognostic value of the expression singly and multiplexed. Epidermal growth factor receptor (EGFR), HER-2, and HER-3 expression were associated with decreased survival. Multivariate analysis showed high HER-2 and HER-3 expression maintained independence as prognostic markers. Hierarchical clustering of expression data defined a small class enriched for HER-2 expression with 40% 10-year survival, compared with 55% using conventional methods. Clustering also revealed a similarly poor-prognostic subgroup coexpressing EGFR and HER-3 (but low for estrogen receptor, progesterone receptor, and HER-2) with a 42% 10-year survival. This work shows that the combined analysis of protein expression improved prognostic classification, and that multiplexed models were superior to any single-marker-based method for prediction of 10-year survival. These methods illustrate a protein-based, multiplexed approach that could more accurately identify patients for targeted therapies.

P53 expression in human rectal tissue after radiotherapy: upregulation in normal mucosa versus functional loss in rectal carcinomas

Purpose: In vitro, ionizing radiation of epithelial cells leads to upregulation of wild-type p53 and subsequent induction of p21 waf1. The effect of radiotherapy (RT) on the expression of these proteins in patients is unknown. We assessed the influence of RT on the expression of p53 and p21 waf1 in normal mucosa and rectal carcinomas in vivo. Methods: Tumor and normal tissue samples were derived from rectal cancer patients randomized in a clinical trial in which the value of preoperative RT was evaluated. p53 and p21 waf1 expression was determined in 51 irradiated and 52 nonirradiated patients using immunohistochemistry. Results: In normal mucosa, both p53 and p21 waf1 were strongly upregulated after RT compared with the expression in unirradiated normal tissue ( p <0.001). In tumor cells, no significant difference in the expression of p53 or p21 waf1 was found in the irradiated vs. nonirradiated group. In the few rectal tumors with wild-type p53, induction of p53 after RT did not necessarily lead to upregulation of p21 waf1. Conclusion: These findings demonstrate that in normal mucosa, a functional p53–p21 waf1 pathway is present, whereas in tumor cells it is defective in almost all cases because of either p53 mutation or down- or upstream disruption in tumors with wild-type p53. Therefore, we believe that the role of p53 expression as a single prognostic marker in rectal cancer needs reconsideration.