Accurate Prognostic Indicator Research Articles

Comparatively tested potential risk factors across survivors and non-survivors critically patients

Background: The risk factors associated with mortality in critically ill patients have been the subject of numerous studies. However, a considerable amount of variation is evident when one considers the dispersion of patients, the geographical spread, and the classification of healthcare establishments. Aim: The purpose of this study was to compare potential risk factors between Survivors and Non-Survivors, including demographics, anthropometrics, kidney and liver indices, complete blood counts, and biochemical assays. Patients whose condition is critical. Methods: An ICU retrospective investigation was conducted in Jordan, where critically ill patients with surgical and medical conditions were examined. Using the Electronic Medical Record System (Hakeem), the study analysed data and classified patients into two cohorts according to their survival status. Demographic information, clinical characteristics, insulin administration rate, blood glucose levels, dosing schedules for vasopressors, and the burden of comorbidities were all included in the data. The research was granted approval by the Institutional Review Board committee of the Royal Medical Services, Jordan. Results: The research examined the male-to-female ratios among COVID-19 patients and classified them into six distinct age groups. A significant proportion of critical patients, ranging in age from 50 to 60, exhibited elevated corrected sodium levels and a diminished normontraemia status. Higher albumin levels and mean arterial pressures were associated with survivors, whereas a greater proportion of non-survivors were underweight and had a low BMI. A normal temperature was observed in the majority of critically ill patients, whereas non-survivors exhibited elevated fractional blood glucose levels and estimated creatinine clearances. The research emphasises the significance of treatment outcomes and patient demographics. Conclusion: SI may be a more accurate prognostic indicator than non-septic patients due to the effect of norepinephrine, a vasopressor, on heart rate and systolic blood pressure, which may account for the difference in SI values between the two groups.

Prognostic value of sarcopenic visceral obesity in hepatocellular carcinoma treated with TACE.

Although Transartial chemoembolization (TACE) is one of the recommended treatments for hepatocellular carcinoma (HCC), there is always a dispute on the selection of the best beneficiary for treatment. We studied the prognostic value of nutritional markers, obesity, visceral obesity and sarcopenia on survival outcomes under single and different combinations. In a retrospective cohort of 235 patients with HCC at different stages, more accurate comprehensive prognostic factors were obtained by combining and comparing the multifactor hazard ratios (HR) of various parameters, including skeletal muscle index (SMI) and visceral fat index (VFI) obtained by computer tomography, laboratory index albumin-to-globulin (A/G) ratio, anthropometric body mass index (BMI) and other parameters. The study cohort was dominated by men (73.6%), with a median age of 54 years. According to the survival outcome of HCC patients, we obtained the ideal sex cutoff value of VFI: ≥40.54 cm 2 /m 2 for males (the receiver operating characteristic curve [ROC] = 0.764, P < .001) and ≥ 43.19 cm 2 /m 2 for females (ROC = 0.718, P < .05). According to the results of multifactor analysis, sarcopenic visceral obesity (HR = 8.35, 95% confidence intervals [CI] = [4.96, 14.05], P < .001) is more effective than any single or combined prognosis assessment, including sarcopenic dystrophy (HR = 2.70, 95% CI = [1.85, 3.95], P < .001), sarcopenic obesity (HR = 5.23, 95% CI = [3.41, 8.02], P < .001), sarcopenia (HR = 5.74, 95% CI = [3.61, 9.11], P < .001) and visceral obesity (HR = 3.44, 95% CI = [2.24, 5.27], P < .001). Sarcopenic visceral obesity, defined by SMI and VFI, is a more objective and accurate prognostic indicator of HCC.

Mitochondrial DNA methylation is a predictor of immunotherapy response and prognosis in breast cancer: scRNA-seq and bulk-seq data insights.

Alterations in Mitochondrial DNA methylation (MTDM) exist in many tumors, but their role in breast cancer (BC) development remains unclear. We analyzed BC patient data by combining scRNA-seq and bulk sequencing. Weighted co-expression network analysis (WGCNA) of TCGA data identified mitochondrial DNA methylation (MTDM)-associated genes in BC. COX regression and LASSO regression were used to build prognostic models. The biological function of MTDM was assessed using various methods, such as signaling pathway enrichment analysis, copynumber karyotyping analysis, and quantitative analysis of the cell proliferation rate. We also evaluated MTDM-mediated alterations in the immune microenvironment using immune microenvironment, microsatellite instability, mutation, unsupervised clustering, malignant cell subtype differentiation, immune cell subtype differentiation, and cell-communication signature analyses. Finally, we performed cellular experiments to validate the role of the MTDM-associated prognostic gene NCAPD3 in BC. In this study, MTDM-associated prognostic models divided BC patients into high/low MTDM groups in TCGA/GEO datasets. The difference in survival time between the two groups was statistically significant (P<0.001). We found that high MTDM status was positively correlated with tumor cell proliferation. We analyzed the immune microenvironment and found that low-MTDM group had higher immune checkpoint gene expression/immune cell infiltration, which could lead to potential benefits from immunotherapy. In contrast, the high MTDM group had higher proliferation rates and levels of CD8+T cell exhaustion, which may be related to the secretion of GDF15 by malignant breast epithelial cells with a high MTDM status. Cellular experiments validated the role of the MTDM-associated prognostic gene NCAPD3 (the gene most positively correlated with epithelial malignant cell proliferation in the model) in BC. Knockdown of NCAPD3 significantly reduced the activity and proliferation of MDA-MB-231 and BCAP-37 cells, and significantly reduced their migration ability of BCAP-37 cell line. This study presented a holistic evaluation of the multifaceted roles of MTDM in BC. The analysis of MTDM levels not only enables the prediction of response to immunotherapy but also serves as an accurate prognostic indicator for patients with BC. These insightful discoveries provide novel perspectives on tumor immunity and have the potentially to revolutionize the diagnosis and treatment of BC.

LncRNA HClnc1 facilitates hepatocellular carcinoma progression by regulating PKM2 signaling and indicates poor survival outcome after hepatectomy.

Long noncoding RNAs (lncRNAs) are key mediators with a wide range of pathophysiological functions, but their role in human hepatocellular carcinoma (HCC) is still unclear. An unbiased microarray study evaluated a novel lncRNA, HClnc1, that is linked to the development of HCC. In vitro cell proliferation assays and an in vivo xenotransplanted HCC tumor model were performed to determine its functions, followed by antisense oligo-coupled mass spectrometry to identify HClnc1-interacting proteins. To study relevant signaling pathways, in vitro experiments were performed, including chromatin isolation by RNA purification, RNA immunoprecipitation, luciferase, and RNA pull-down assay. HClnc1 levels were considerably greater in patients with advanced tumor-node-metastatic stages, and it was found to be inversely connected to survival rates. Moreover, the proliferative and invasive potential of the HCC cells was attenuated by HClnc1 RNA knockdown in vitro, while HCC tumor growth and metastasis were found to be reduced in vivo. HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2-STAT3 signaling. HClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. HClnc1 is not only a more accurate prognostic indicator of HCC but also a potential therapeutic target for HCC treatment.

Combined proliferation and apoptosis index provides better risk stratification in breast cancer.

Breast cancer (BC) risk stratification is critical for predicting behaviour and guiding management decision-making. Despite the well-established prognostic value of cellular proliferation in BC, the interplay between proliferation and apoptosis remains to be defined. In this study, we hypothesised that the combined proliferation and apoptosis indices can provide a more accurate in-vivo growth rate measure and a precise prognostic predictor. Apoptotic and mitotic figures were counted in whole slide images (WSI) generated from haematoxylin and eosin-stained sections of 1545 BC cases derived from two well-defined BC cohorts. Counts were carried out visually within defined areas. There was a significant correlation between mitosis and apoptosis scores. High apoptotic counts were associated with features of aggressive behaviour, including high grade, high pleomorphism score and hormonal receptor negativity. Although the mitotic index (MI) and apoptotic index (AI) were independent prognostic indicators, the prognostic value was synergistically higher when combined. BCpatients with a high combined AI and MI had theshortest survival. Replacing the mitosis score with the mitosis-apoptosis index in the Nottingham grading system revealed that the modified grade with the new score had a higher significant association with BC-specific survival with a higher hazard ratio. Apoptotic figures count provides additional prognostic value in BC when combined with MI; such a combination can be implemented to assess the behaviour of BC and provides an accurate prognostic indicator. This can be considered when using artificial intelligence algorithms to assess proliferation in BC.

A novel exosome-derived prognostic signature and risk stratification for breast cancer based on multi-omics and systematic biological heterogeneity

Tumor heterogeneity remains a major challenge for disease subtyping, risk stratification, and accurate clinical management. Exosome-based liquid biopsy can effectively overcome the limitations of tissue biopsy, achieving minimal invasion, multi-point dynamic monitoring, and good prognosis assessment, and has broad clinical prospects. However, there is still lacking comprehensive analysis of tumor-derived exosome (TDE)-based stratification of risk patients and prognostic assessment for breast cancer with systematic dissection of biological heterogeneity. In this study, the robust corroborative analysis for biomarker discovery (RCABD) strategy was used for the identification of exosome molecules, differential expression verification, risk prediction modeling, heterogenous dissection with multi-ome (6101 molecules), our ExoBCD database (306 molecules), and 53 independent studies (481 molecules). Our results showed that a 10-molecule exosome-derived signature (exoSIG) could successfully fulfill breast cancer risk stratification, making it a novel and accurate exosome prognostic indicator (Cox P = 9.9E-04, HR = 3.3, 95% CI 1.6–6.8). Interestingly, HLA-DQB2 and COL17A1, closely related to tumor metastasis, achieved high performance in prognosis prediction (86.35% contribution) and accuracy (Log-rank P = 0.028, AUC = 85.42%). With the combined information of patient age and tumor stage, they formed a bimolecular risk signature (Clinmin-exoSIG) and a convenient nomogram as operable tools for clinical applications. In conclusion, as an extension of ExoBCD, this study conducted systematic analyses to identify prognostic multi-molecular panel and risk signature, stratify patients and dissect biological heterogeneity based on breast cancer exosomes from a multi-omics perspective. Our results provide an important reference for in-depth exploration of the "biological heterogeneity - risk stratification - prognosis prediction".

Clinical parameters at time of admission as prognostic indicators in cats presented for trauma to an emergency centre in New Zealand: a retrospective analysis.

The aims of this study were to describe the clinical features of cats presented for trauma in a first-opinion and referral teaching hospital in New Zealand, and to determine the relationship between those features and outcome. The electronic medical records of cats presented for trauma to the Massey University Pet Emergency Centre between September 2013 and January 2019 were examined, from which the signalment, clinical parameters and patient outcomes were extracted. Cases were assigned an Animal Trauma Triage (ATT) score and Modified Glasgow Coma Scale (MGCS) score. Variables were selected for inclusion in a logistic regression model to predict survival, and backward elimination was used to find the minimal significant model. In total, 530 cats met the inclusion criteria. The cause of injury was not known in the majority of cases (38.0%). The most common location of injury was the hindlimbs/pelvis/tail (n = 247; 41%), and skin lacerations/abrasions were the most common specific injury. Multivariate analysis revealed altered mentation (odds ratio [OR] 0.31, P = 0.029), hypothermia (rectal temperature <37.8°C [<100.04°F]; OR 0.45, P = 0.015) and an ATT score ⩾5 (OR 0.13, P <0.001) to be statistically significantly associated with mortality. Altered mentation and hypothermia are easily measurable perfusion parameter abnormalities associated with mortality in cats presenting with trauma. The ATT score appears to be an accurate prognostic indicator in cats presenting with trauma in New Zealand. These results highlight the importance of incorporating a hands-on triage examination in each cat that presents as an emergency after trauma.

Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System.

Aim: Increasing studies have demonstrated lymph node ratio (LNR) to be an accurate prognostic indicator in breast cancer and an alternative to pN staging; however, the AJCC-TNM staging system classified apical or infraclavicular/ipsilateral supraclavicular lymph node-positive (APN(+)) patients with a worse prognosis as the pN3 stage. Until now, different reports on LNR in breast cancer have ignored this possibility. Consequently, it is necessary to discuss the role of APN(+) patients in the LNR system to obtain a precise LNR that predicts the prognosis accurately. Materials and Methods: We collected data on 10,120 breast cancer patients, including 3,936 lymph node-positive patients (3,283 APN(−) and 653 APN(+) patients), who visited our hospital from 2007 to 2012. Then we applied X-tile analysis to calculate cut-off values and conduct survival analysis and multivariate analysis to evaluate patients’ prognosis. Results: We confirmed that some APN(+) patients were mis-subgrouped according to previously reported LNR, indicating that APN(+) patients should be excluded in the application of LNR to predict prognosis. Then we applied X-tile analysis to calculate two cut-off values (0.15 and 0.34) for LNR-APN(−) patients and conducted survival analysis and found that LNR-APN(−) staging was superior to pN staging in predicting the prognosis of APN(−) breast cancer patients. Conclusion: From this study, we conclude that excluding APN(+) patients is the most necessary condition for effective implementation of the LNR system. LNR-APN(−) staging could be a more comprehensive approach in predicting prognosis and guiding clinicians to provide accurate and appropriate treatment.

Prognostic value of neutrophil-to-lymphocyte ratio in cirrhosis patients undergoing transjugular intrahepatic portosystemic shunt.

The neutrophil-to-lymphocyte-ratio (NLR) is used as an inflammatory index and has proven to be an accurate prognostic indicator for decompensated cirrhotics; however, its role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) has not been evaluated. We examined whether NLR is associated with mortality in decompensated cirrhosis patients undergoing TIPS. We performed a retrospective review of 268 decompensated cirrhotics who underwent TIPS from January 2011 to December 2015 at an academic medical center. NLR, patient demographics, manifestations of cirrhosis, TIPS indications and mortality were recorded. Univariate and multivariate Cox regression analyses for prognostic factors associated with 30-day and 90-day post TIPS mortality were performed. A total of 129 (48%) patients received TIPS for refractory ascites with 79 (29%) for variceal bleeding, 14 (5%) for hepatic hydrothorax, and 46 (17%) for other indications. Cirrhosis etiology included hepatitis C (36%), alcohol (28%), nonalcoholic steatohepatitis (20%), or other (15%). Median NLR was 4.42 (IQR 2.75-7.19). Univariate and multivariate analysis showed NLR as an independent predictive factor of 30-day and 90-day mortality. Furthermore, in patients with a Model of End-Stage Liver Disease (MELD) ≤ 15, NLR is superior to MELD/MELD-Na score in predicting 30-day and 90-day mortality. In patients with MELD > 15, MELD/MELD-Na score is superior to NLR. Our data indicate that elevated NLR independently predicts 30-day and 90-day mortality. In patients with a MELD ≤ 15, NLR is a better prognostic factor than MELD or MELD-Na in predicting short-term mortality.

Cardiopulmonary Resuscitation-Induced Hardware Failure After Surgical Stabilization of Flail Chest

Flail chest occurs when three or more ribs have concurrent fractures in two or more places. Flail chest is a marker of injury severity and is associated with increased morbidity and mortality. The management of flail chest includes multiple nonoperative components in addition to surgical stabilization, which has been shown to lower mortality rates to those of multiple rib fractures with a stable chest wall (i.e., no flail chest). The resulting stability of the chest wall may be a more accurate prognostic indicator than the actual number of ribs fractured. Surgical stabilization has been associated with various complications. The overall incidence of hardware failure is relatively rare and often involves the anterolateral and lateral regions of the chest wall. We present a unique case of a 48-year-old male involved in a motor vehicle accident with multiple traumatic injuries, including flail chest. He ultimately underwent surgical stabilization across six separate ribs in nine total locations. The patient’s condition deteriorated several weeks later, and he required cardiopulmonary resuscitation. High impact forces caused hardware failure in three separate locations along the chest wall, i.e., anteriorly, anterolaterally, and posterolaterally. The most significant failure occurred anteriorly with sternal plate and screw separation. We suspect that hardware failure in the anterior and anterolateral regions indicates that the sternum and costochondral junction may be dynamic areas of the chest wall that dissipate forces differently than do the bone of ribs.

A Lack of Practice Effects on Memory Tasks Predicts Conversion to Alzheimer Disease in Patients With Amnestic Mild Cognitive Impairment.

The aim of the current study was to test the accuracy of practice effects, that is, improvement in test performance due to repeated neuropsychological evaluations, in identifying patients with amnestic mild cognitive impairment (a-MCI) at greater risk of conversion to Alzheimer disease (AD). For this purpose, we conducted a longitudinal study of 54 patients diagnosed with a-MCI at the first assessment and followed-up for 4 years. During this time, 18 patients converted to AD. Baseline and 6- to 12-month follow-up performances on a large set of neuropsychological tests were analyzed to determine their diagnostic ability to predict later conversion to dementia. Results demonstrate that a lack of practice effects on episodic memory tests is an accurate prognostic indicator of late conversion to AD in a-MCI patients. In fact, even though the performance of both groups was substantially comparable at the baseline evaluation, stable a-MCI patients greatly improved their memory performance at retest after 6 to 12 months; instead, scores of converter a-MCI remained stable or decreased passing from baseline to follow-up. Standardized z-change scores on memory tasks, which were computed as a reliable measure of performance change, classified group membership with very good overall accuracy, which was higher than the classification of converter and stable a-MCIs provided by baseline or follow-up scores. We hypothesize that the lack of practice effects on memory tasks mirrors the early involvement of medial temporal lobe areas in converter a-MCI that are fundamental for the consolidation of new memory traces.

A Simple and Practical Scoring System for Radiosurgical Treatment in Patients with Brain Metastases

Background: The study aimed to investigate the prognostic factors for patients with brain metastases undergoing radiosurgical treatment and to introduce a simple and practical scoring system for the prediction of survival time. Methods: We retrospectively analyzed data for 311 patients treated with Gamma Knife radiosurgery at a single institute. The mean age at time of treatment was 60 years (range 23–86 years), and the median Karnofsky performance status (KPS) score was 90 (range 60–100). Using a new prognostic index, the prognostic index for brain metastases (PIBM), the patients were categorized into 3 groups according to the primary tumor status and KPS score. We performed survival analysis and compared the prognostic ability of the PIBM with other published indices. Results: During the median follow-up duration of 8.2 months (range 0.1–109 months), the median overall survival time was 9.1 months. Stable primary tumor status (hazard ratio [HR] 0.497, 95% confidence interval [CI] 0.321–0.769, p = 0.002) and KPS score ≥90 (HR 1.407, 95% CI 1.018–1.946, p = 0.039) significantly predicted longer overall survival. The PIBM showed the lowest Akaike information criterion value and the highest integrated area under the curve value compared with other prognostic indices. Conclusions: The PIBM may be a more accurate prognostic indicator than other published indices. Although this new and practical prognostic index requires further validation in larger cohort studies, we suggest that the PIBM could be useful to predict survival time and inform appropriate management of patients with brain metastases.

Oncogenic mechanism of soluble Keratin 17 offers potential therapeutic vulnerability in pancreatic cancer

CLINICAL NEED &amp; OBJECTIVESOur group found that Keratin 17 (K17), an intermediate filament (IF), is a tumor cell‐specific marker of aggressive pancreatic ductal adenocarcinoma (PDAC), and that the detection of K17 by immunohistochemistry level is a more accurate prognostic indicator than transcriptomic subtyping. We determined that K17 can act as an oncoprotein after transitioning from its “insoluble” cytoskeleton form to a “soluble” form that can regulate cell cycle progression. In patients, mice, and PDAC cell lines, the soluble fraction of K17 exists as full length (flK17) and caspase‐cleaved peptide (ccK17), each with potentially unique tumorigenic capacity. Literature suggests that post‐translational modifications (PTMs) are necessary to regulate these and other IF dynamics, though the mechanisms behind K17 solubilization in PDAC are still unclear. Thus, our aims are to 1) determine the mechanisms regulating K17 dynamics, 2) demonstrate inhibited cell cycle progression and tumor growth following disruption of these mechanisms, and 3) verify soluble K17 as a robust negative prognostic biomarker of PDAC.METHODS &amp; RESULTSIn a PDAC tumor mouse model, we show, independent of total K17 protein amount, that the percent of soluble ccK17 in tumor cells is negatively prognostic. Work is ongoing to validate this finding in human PDAC samples. We sequenced both the soluble and cytoskeletal insoluble forms of K17 from primary PDACs using liquid chromatography mass spectrometry (LC‐MS) and identified that K17 is phosphorylated on several N‐terminal serine residues. Specifically, we reproducibly identified phosphorylation of a semi‐conserved IF motif that may promote caspase cleavage and solubilization. Ser/Thr phosphatase inhibition in vitro demonstrated that phosphorylation is necessary to trigger K17 solubilization followed by nuclear translocation. Mutagenesis of serine sites is ongoing to determine the specific motifs regulating K17. Using an unbiased kinase inhibitor screen and follow‐up pharmacologic analyses, we identified that polo‐like kinase 1 (PLK1) likely phosphorylates K17. Further studies are underway to validate K17 as a key mediator of PLK1 inhibitor sensitivity in PDAC.CONCLUSIONPhosphorylation is an important regulator of K17 dynamics in PDAC, promoting solubilization and, in some cases, caspase cleavage. Our results suggest that soluble K17 may have a functional role in promoting tumor aggression. Inhibiting kinases that phosphorylate K17 could impact tumor growth by blocking K17 solubilization/cleavage and this line of research could accelerate the development of more effective treatments, coupled to soluble K17 testing as a predictive biomarker for PDAC.Support or Funding InformationThis work was partially supported by the 2018 Pancreatic Cancer Action Network Translational Research Grant (K.R.S.).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prognostic value of early hemodynamic improvement in patients with acute kidney injury and hemodynamic instability treated with continuous renal replacement therapy

BackgroundSince description of continuous renal replacement therapy (CRRT), these therapies provided improvement in hemodynamic parameters while reducing need for vasopressors in shock. Our aim is to determine whether hemodynamic improvement after 24 h of CRRT is a strong predictor of short term survival. MethodsIn a prospective observational study we enrolled 30 patients admitted to the intensive care unit (ICU)with acute kidney injury (AKI)and hemodynamic instability. AKI defined according to KDIGO criteria. All patients were subjected to continuous renal replacement therapy (CRRT). Based on the hemodynamic response 24 h after CRRT, patients were classified into responders (defined as having a 20% reduction in norepinephrine dosage or a 20% rise in MAP with no increase in norepinephrine), compared with nonresponders . All patients were followed up for 15 days after withdrawal of CRRT. Results of the 30 patients studied, 12 (40%) were responders and 18 (60%) were nonresponders. Responders showed higher mean arterial pressure and urine output during CRRT. SOFA score tended to increase significantly in nonresponders on day 3 (SOFA3) and day 4 (SOFA4) compared to nonresponders (P = 0.01, P = 0.001; respectively). During a 15 days follow-up period, the mortality rate among non responders was 100%, compared to 25% among responders (18 versus 3; P = 0.001). ConclusionEarly hemodynamic improvement after CRRT is strong predictor of short term mortality. Of all scoring systems , post CRRT SOFA score is the most accurate prognostic indicator for mortality.

Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis.

An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS).We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively.Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR.

ED13.02 Tissue-Based Biomarkers

ED13.02 Tissue-Based Biomarkers

Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival.

Gray-Level Co-Occurrence Matrix Texture Analysis of Breast Tumor Images in Prognosis of Distant Metastasis Risk.

Owing to exceptional heterogeneity in the outcome of invasive breast cancer it is essential to develop highly accurate prognostic tools for effective therapeutic management. Based on this pressing need, we aimed to improve breast cancer prognosis by exploring the prognostic value of tumor histology image analysis. Patient group (n=78) selection was based on invasive breast cancer diagnosis without systemic treatment with a median follow-up of 147 months. Gray-level co-occurrence matrix texture analysis was performed retrospectively on primary tumor tissue section digital images stained either nonspecifically with hematoxylin and eosin or specifically with a pan-cytokeratin antibody cocktail for epithelial malignant cells. Univariate analysis revealed stronger association with metastasis risk by texture analysis when compared with clinicopathological parameters. The combination of individual clinicopathological and texture variables into composite scores resulted in further powerful enhancement of prognostic performance, with an accuracy of up to 90%, discrimination efficiency by the area under the curve [95% confidence interval (CI)] of 0.94 (0.87-0.99) and hazard ratio (95% CI) of 20.1 (7.5-109.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the models are generalizable. Whereas further validation is needed on an external set of patients, this preliminary study indicates the potential use of primary breast tumor histology texture as a highly accurate, simple, and cost-effective prognostic indicator of distant metastasis risk.

SMICA and its emerging role as a prognostic and diagnostic indicator in systemic malignancies besides hepatocellular carcinoma

I read the recent article by Li et al.[1] with great interest. Intriguingly, emerging evidence suggests that soluble major histocompatibility complex class I–related chain A (sMICA) may be an important diagnostic and prognostic marker in a number of systemic malignancies besides hepatocellular carcinoma. For instance, higher sMICA levels are seen in oral squamous cell carcinomas of high TNM stages[2]. Thus, sMICA can be used as a diagnostic and prognostic indicator of advanced stage and especially lymph node metastasis in oral carcinomas. Tamaki et al.[3] have shown that patients with oral carcinomas with high sMICA levels (≥50 ng/L) have lower overall survival rates than do patients with low sMICA levels (<50 ng/L). sMICA may also be used as a diagnostic biomarker in pancreatic ductal adenocarcinomas. When used in conjunction with serum uric acid and sMICB, sMICA provides additional information on the prognosis of pancreatic ductal adenocarcinoma[4]. sMICA also exhibits higher specificity and sensitivity when compared with CA19-9, a known marker for pancreatic ductal adenocarcinomas. Indeed, Chung et al.[4] reported a sensitivity of 76.5% and a specificity of 91.2% for sMICA, while a sensitivity of 73.5% and a specificity of 90.9% for CA19-9. Moreover, sMICA levels were found to be closely related to distant metastasis of pancreatic cancer. Collectively, the three markers sMICA, sMICB, and CA19-9 provide more information than did CA19-9 alone. In colorectal cancer, sMICA levels alter in the advanced stages. These elevated levels may prove to be a highly sensitive marker for advanced stage colorectal cancer[5]. A close relationship exists between the TNM stage and sMICA levels in breast cancers; as with other cancers described here, breast cancers of advanced TNM stage exhibit higher sMICA levels. sMICA contributes to immunological escape of mammary neoplasms by impairing immune surveillance mediated by natural killer cells[6]. At the same time, it attenuates natural killer group 2, member D (NKG2D) expression. A simultaneous attenuation effect is seen in interferon-gamma secretion. Poorly differentiated and late-stage osteosarcomas demonstrate higher sMICA levels, making sMICA an excellent prognostic and diagnostic indicator of advanced stages in osteosarcomas[7]. sMICA is also a highly accurate independent prognostic indicator in multiple myelomas. Poor progression-free survival rates are seen in multiple myelomas with sMICA levels greater than 305 pg/mL[8]. The above examples clearly illustrate the diagnostic and prognostic significance of sMICA in systemic cancers and the need for further studies to establish similar plausible relationships in other systemic malignancies.

Butyrylcholinesterase as a prognostic marker: a review of the literature

BackgroundButyrylcholinesterase (BChE) is an α-glycoprotein synthesized in the liver. Its serum level decreases in many clinical conditions such as acute and chronic liver damage, inflammation, injury and infections, and malnutrition.Methods and resultsThis review collects the main evidence on the emerging role of butyrylcholinesterase as a prognostic marker of liver and nonliver diseases as well as a marker of protein-energy malnutrition and obesity. In fact, serum concentrations and BChE activity seem to accurately reflect the availability of amino acidic substrates and/or derangement in protein synthesis due to hepatocellular damage. In cancer, with or without liver impairment, serum BChE levels serve as an accurate functional and prognostic indicator, useful for monitoring clinical and therapeutic interventions according to patients’ prognosis. In the absence of inflammation, BChE could also serve as an index of the effectiveness of nutritional support.ConclusionsSerum BChE assessment should be included in routine clinical diagnostic procedures to evaluate patient clinical conditions, in particular in cases of inflammation and/or protein-energy malnutrition.