Prognostic Classification Of Patients Research Articles

Identification of an immune-related signature as a prognostic classifier for patients with early-stage head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the most common type and accounts for 90% of all head and neck cancer cases. Despite advances in early diagnosis and treatment strategies-chemotherapy, surgical resection, and radiotherapy-5-year survival remains grim. For patients with early-stage HNSCC, accurately predicting clinical outcomes is challenging. Considering the pivotal role of the immune system in HNSCC, we developed a reliable immune-related gene signature (IRGS) and explored its predictive accuracy in patients with early-stage HNSCC. We examined immune gene expression profiles and clinical information from 230 early-stage HNSCC specimens, including 100 cases from The Cancer Genome Atlas (TCGA), 49 cases from the Gene Expression Omnibus (GEO; GSE65858), and 81 cases from an independent clinical cohort. The prognostic signature was constructed using Kaplan-Meier analysis and the least absolute shrinkage and selection operator (LASSO) Cox algorithm. We also explored the IRGS-related biological pathways and immune landscape using bioinformatics analysis. A nine-immune-gene signature was generated to significantly stratify patients into high and low-risk groups. High risk patients exhibited shorter survival time [hazard ratio (HR) =13.795, 95% confidence interval (CI): 3.275-58.109, P<0.001]. The signature demonstrated robust prognostic ability in the training and validation sets and could independently predict overall survival (OS) and relapse-free survival (RFS). Subsequently, the receiver operating characteristic (ROC) curve and C-index confirmed the signature's predictive accuracy compared to clinical parameters. Additionally, cases classified as low risk showed more immune cell infiltration than high-risk cases. Our novel IRGS is a reliable and robust classifier for accurate patient stratification and prognostic evaluation. Future studies will attempt to affirm the signature's clinical application to early-stage HNSCC.

Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade

BackgroundSubgroup analyses of randomized trials suggest the superiority of immune checkpoint inhibitor-based therapy over chemotherapy in patients with mismatch-repair deficient (dMMR) and/or microsatellite instability-high (MSI-high) advanced gastric or gastroesophageal junction...

Development and Validation of a Robust Apoptosis-Related Prognostic Classifier in Patients with Osteosarcoma

Background: Apoptosis plays an important role in the tumorigenesis and the development of osteosarcoma, but the reliable biomarkers for individual treatment and prognosis of osteosarcoma based on apoptosis is lacking. Methods: A total of 1476 apoptosis-related genes were extracted from pathways and biological processes associated with apoptosis downloaded from MSigDB. All of those genes were used to identified the prognosis-related genes by univariate cox regression in the TARGET dataset and the ARS was constructed using the LASSO regression. The performance of the classifier was verified in the training and validation groups. The infiltration of immune cells and the expression levels of the immune checkpoint in different groups were also analyzed. Finally, a nomogram based on ARS and other Clinicopathological factors was constructed to facilitate clinical application. Results: ARS containing 22 apoptosis-related genes were identified, and its predictive ability performed well in both the training and validation groups. Macrophages M1 were highly expressed in the low-score group, and NK cells resting was highly expressed in the high-score group. The samples with low-score had higher expression of CTLA4 and PDL1. A nomogram with excellent predictive effectiveness (AUC= 0.932, 0.984, 0.939, 0.939, 0.948) was constructed to facilitate clinical decision-making. Conclusion: A prognostic classifier based on 22 apoptosis-related genes and a nomogram were constructed to predict the overall survival of patients with osteosarcoma. The classifier also provides a reference for selecting suitable patients for immunotherapy and targeted therapy.

A universal molecular prognostic score for gastrointestinal tumors

Colorectal and gastric cancers are a leading cause of cancer deaths in developed countries. Precise estimation of prognosis is important with regard to clinical decision making for individuals with such cancers. We here comprehensively compiled a complete atlas of prognostic genes based on an integrated meta-analysis of one of the largest assembled colorectal cancer cohorts. A simple yet robust machine learning approach was then applied to establish a universal molecular prognostic score (mPS_colon) that relies on the expression status of only 16 genes and which was validated with independent data sets. This score was found to be an independent prognostic indicator in multivariate models including cancer stage, to be valid independent of tumor characteristics or patient ethnicity, and to be also applicable to gastric cancer. We conclude that mPS_colon is a universal prognostic classifier for patients with gastrointestinal cancers and that it should prove informative for optimization of personalized therapy for such patients.

Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery. Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line. Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan-Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (p < 0.0001) than in the low-risk group (26.9months for TTR, 95% CI 22.4-31.5) than in the high-risk group (14.5months for TTR, 95% CI 10.6-18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro. Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.

Histopathological prognostic markers in metastatic lung adenocarcinoma, validation of stromal fibrosis and immunoscore as easy to interpret findings and their correlation with survival.

e21566 Background: Several histopathological markers have been associated with immune system activity and its relationship with clinical outcomes in lung cancer. Determination of tumor infiltrating lymphocytes as well as specific subpopulations could reveal cytotoxic potential. Additionally, changes in stromal composition and fibrosis could also reflect potential cellular interactions with the tumor lesions. In this study we validate these two findings as potential prognostic factors. Methods: A retrospective cohort analysis of patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. In addition to clinical outcomes, the percentage of stromal fibrosis and immunoscore were estimated for all biopsy samples by a trained oncological pathologist. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80 and 19% of prior cigarette exposure (26 patients) was identified in the cohort. Median overall survival of the cohort was 27.1 months (95%CI 22.1-NA) and progression free survival of 19.4 months (95%CI 18-24.5 months). Percentage of fibrous stroma and immunoscore were associated with a benefit in both OS and PFS. For patients who presented with a low stromal fibrosis, defined as harboring less than 10%, OS reached a median of 25.1 months (95%CI 21.5- 40.5 months) compared to 38.7 months for patients with high fibrosis (95%CI 27.7 months – NA), (p = 0.02). In terms of immunoscore, values under 40% were associated with a longer median OS (38.7 months, [95%CI 31.3- 58.6 months] vs 22.1 months [95%CI19.8- 42.3 months], p &lt; 0.001). Immunoscore and stromal fibrosis were not codependent variables (p &lt; 0.001), suggesting that these markers offer independent prognostic value with regards to OS. Conclusions: Stromal fibrosis and immunoscore serve as prognostic factors that could be easily interpreted and evaluated in order to offer prognostic classification of patients with metastatic adenocarcinoma of the lung.

Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

Histological ‘phenotypic subtypes’ that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I–III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I–III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease‐free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II–III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893‐patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p < 0.001) in these patients. In a 146‐patient external cohort, phenotypic subtype independently stratified patients by DFS (p = 0.028), validating their prognostic value. In 1343 SCOT trial patients, the effect of treatment type significantly depended on phenotypic subtype (p interaction = 0.011). Phenotypic subtype independently associated with DFS in stage III patients receiving FOLFOX (p = 0.028). Furthermore, the immune subtype significantly associated with better response to FOLFOX compared to CAPOX adjuvant chemotherapy in stage III patients (p = 0.013). In conclusion, histological phenotypic subtypes are an effective prognostic classification in patients with stage III CRC that associates with risk of recurrence and response to FOLFOX adjuvant chemotherapy.

Prognostic classification for patients with nasopharyngeal carcinoma based on American Joint Committee on cancer staging system T and N categories

Background: This study examined the current American Joint Committee on Cancer (AJCC) 8th edition staging system and proposes a new classification for nasopharyngeal carcinoma (NPC).

Prognostic phenotypic subtypes to predict recurrence and response to adjuvant chemotherapy for colorectal cancer.

205 Background: Histological phenotypic subtypes have been proposed that stratify survival in a discovery cohort of patients with stage I-III colorectal cancer (CRC). However, clinical utility has not been validated nor associations with recurrence and chemotherapy assessed. Therefore, this study assessed prognostic value in patients with stage I-III CRC as well as predictive value for recurrence and chemotherapy response. Methods: Two independent stage I-III CRC patient cohorts were utilized to assess associations between phenotypic subtypes, survival, and recurrence. Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilized to assess associations between phenotypic subtypes and adjuvant chemotherapy response. Log rank analysis compared immune and stromal subtypes. Results: In an 867-patient internal cohort, phenotypic subtype stratified patients by disease-free survival (DFS) (HR 2.18 95% CI 2.26-4.47, p &lt; 0.001); independent of stage and location. The stromal subtype also predicted increased local and distant recurrence (p &lt; 0.001). In a 146-patient external validation cohort, phenotypic subtype significantly stratified patients by DFS (HR 3.43 95% CI 1.60-7.35, p = 0.001). In 1343 SCOT trial patients, phenotypic subtype significantly stratified patients by DFS (HR 1.59 95% CI 1.13-2.25, p = 0.010). Furthermore, there was evidence that the effect of regimen depended on phenotypic subtype (p = 0.048), only significantly stratifying DFS in patients receiving FOLFOX (HR 3.73 95% CI 1.58-8.81, p = 0.003) but not CAPOX (HR 0.84 95% CI 0.56-1.26, p = 0.396) adjuvant chemotherapy. Interestingly, the immune subtype associated with improved DFS in patients receiving FOLFOX compared to CAPOX adjuvant chemotherapy (HR 3.40 95% CI 1.41-8.19, p = 0.006). Whereas patients with a stromal subtype trended towards improved DFS in patients receiving CAPOX compared to FOLFOX adjuvant chemotherapy (HR 0.72 95% CI 0.50-1.05 p = 0.088). Conclusions: Histological phenotypic subtypes are an effective independent prognostic classification for patients with stage I-III CRC that can predict response to FOLFOX adjuvant chemotherapy as well as the presence of local and distant recurrence.

Abstract P3-10-13: Dual targeting of androgen receptor and IKK alpha is a potential therapeutic strategy for triple negative breast cancer

Abstract Background There are limited treatments for triple negative breast cancer (TNBC) patients and an unmet need for targeted approaches in these patients. In the last 4-5 years, the prevalence of high androgen receptor (AR) expression in TNBCs has been noted in up to 50% of tumors suggesting it has clinical relevance. The non-canonical NF-kB pathway is also upregulated in this patient group and it has been reported that that there is crosstalk between these pathways. Therefore the aim of this study was to examine the expression of IKKα and AR in breast cancer tissue samples, to assess if combining these markers increased prognostic power. Methods Immunohistochemistry was performed on tissue microarray of 410 patients to assess proteins level of IKK alpha and AR. Protein expression levels were assessed using the weighted histoscore (WHS) method. The median was employed as the cut off for IKK alpha and 1% as cut off for AR. Expression was analyzed for associations with cancer-specific survival (CSS) and recurrence-free survival (RFS). Results In a cohort of 370 breast cancers nether AR nor IKK alpha alone or combined were associated with CSS or RFS. Stratifying patients by ER status did not impact CSS or RFS. However, in TNBC patients (n=82) high expression of AR was associated with shorter CSS (HR 2.55 95 CI 1.61-5.59, p=0.013). To assess if combining AR and IKK alpha increased prognostic power, AR and IKK alpha were combined into a single score: 0= low expression of both or high expression of one and 1= high expression of both. In the full cohort or when stratified by ER status the score was not associated with CSS or RFS, however in TNBC the combined score potentiated the effect observed with AR alone, (HR 1.68 95 CI 1.20-2.33, p=0.001). Patient CSS was stratified from 11.5 years to 4.6 years and was independently associated with CSS when compared with common clinicopathological factors (HR 1.56 95CI 1.11-2.21, p=0.011). In addition, the combined score was associated with decrease radiotherapy use (p=0.032), increased recurrence rate (p=0.014), decreased cytotoxic T cells (p=0.007), B cells (p=0.043) and macrophages (p=0.037). Conclusions A combined AR and IKK alpha score is an independent prognostic classification for patients with TNBC. Patients with high expression of both AR and IKK alpha a significantly reduced survival and were immune cell cold. This study suggests that this patient group will not benefit from immunotherapy but dual targeting with anti-androgens and IKK alpha selective inhibitors could offer a novel therapeutic strategy for this patient group. Citation Format: Roseweir AK, Khongthong P, Dickson K, Bennett L, Edwards J. Dual targeting of androgen receptor and IKK alpha is a potential therapeutic strategy for triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-13.

Development and Validation of a MRI-Based Radiomics Prognostic Classifier in Patients with Primary Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common and deadly type of primary malignant tumor of the central nervous system. Accurate risk stratification is vital for a more personalized approach in GBM management. The purpose of this study is to develop and validate a MRI-based prognostic quantitative radiomics classifier in patients with newly diagnosed GBM and to evaluate whether the classifier allows stratification with improved accuracy over the clinical and qualitative imaging features risk models. Clinical and MR imaging data of 127 GBM patients were obtained from the Cancer Genome Atlas and the Cancer Imaging Archive. Regions of interest corresponding to high signal intensity portions of tumor were drawn on postcontrast T1-weighted imaging (post-T1WI) on the 127 patients (allocated in a 2:1 ratio into a training [n = 85] or validation [n = 42] set), then 3824 radiomics features per patient were extracted. The dimension of these radiomics features were reduced using the minimum redundancy maximum relevance algorithm, then Cox proportional hazard regression model was used to build a radiomics classifier for predicting overall survival (OS). The value of the radiomics classifier beyond clinical (gender, age, Karnofsky performance status, radiation therapy, chemotherapy, and type of resection) and VASARI features for OS was assessed with multivariate Cox proportional hazards model. Time-dependent receiver operating characteristic curve analysis was used to assess the predictive accuracy. A classifier using four post-T1WI-MRI radiomics features built on the training dataset could successfully separate GBM patients into low- or high-risk group with a significantly different OS in training (HR, 6.307 [95% CI, 3.475-11.446]; p < 0.001) and validation set (HR, 3.646 [95% CI, 1.709-7.779]; p < 0.001). The area under receiver operating characteristic curve of radiomics classifier (training, 0.799; validation, 0.815 for 12-month) was higher compared to that of the clinical risk model (Karnofsky performance status, radiation therapy; training, 0.749; validation, 0.670 for 12-month), and none of the qualitative imaging features was associated with OS. The predictive accuracy was further improved when combined the radiomics classifier with clinical data (training, 0.819; validation: 0.851 for 12-month). A classifier using radiomics features allows preoperative prediction of survival and risk stratification of patients with GBM, and it shows improved performance compared to that of clinical and qualitative imaging features models.

Clinicopathological significance of RCAN2 production in gastric carcinoma.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Genes expressed only in cancer tissue may be useful biomarkers for cancer diagnosis and therapeutics. The aims of the present study were to analyse regulator of calcineurin 2 (RCAN2) in a large number of GCs, and to investigate how these expression patterns correlate with clinicopathological parameters and various markers. An immunohistochemical analysis of RCAN2 in 207 GC tissue samples showed that 110 (53%) GCs were positive for RCAN2. RCAN2-positive GCs were more advanced in terms of TNM classification and tumour stage than RCAN2-negative GCs. Furthermore, RCAN2 was an independent prognostic classifier for GC patients. The cell growth and invasiveness of RCAN2 small interfering RNA (siRNA)-transfected GC cell lines were less than those of the negative control siRNA-transfected cell lines, whereas those of RCAN2-transfected cells were significantly increased as compared with those of empty vector-transfected cells. RCAN2 siRNA inhibits the phosphorylation of AKT and p44/p42 (ERK1/2). RCAN2 was colocalised with EGFR, nuclear β-catenin, MMP7, laminin-γ2, VEGF-A, and VEGF-C. These results suggest that RCAN2 is involved in tumour progression and is an independent prognostic classifier in patients with GC.

Is It Possible to Improve Prognostic Classification in Patients Affected by Metastatic Renal Cell Carcinoma With an Intermediate or PoorPrognosis?

The International mRCC (metastatic renal cell carcinoma) Database Consortium (IMDC) is the standard classification for mRCC. We aimed to evaluate the outcomes of a large cohort of patients with an intermediate or a poor prognosis treated with sunitinib using a different cutoff point for IMDC to improve the classification. Patients with an intermediate or a poor prognosis according to the IMDC criteria and treated with sunitinib were included in the present study. A new cutoff point was used to categorize the patients. The new score was validated in an independent cohort of patients. A total of 457 patients were included in the present study. Significant differences in overall survival (OS) were highlighted regarding the number of prognostic factors. Three categories were identified according to the presence of 1 (ie, favorable-intermediate group), 2 (ie, real-intermediate group), and > 2 (ie, poor group) factors. The corresponding median OS periods were 32.9, 20.0, and 8.9 months, with significant differences among the groups. The validation cohort included 389 patients. The median OS period for the favorable-intermediate group, real-intermediate group, and poor group was 34.3, 19.4, and 9.0 months, respectively, with confirmed significant differences among the groups. Our analysis revealed significant differences among patients with an intermediate prognosis using the IMDC prognostic factors. Further investigations to optimize the use of available and upcoming therapies are required.

Abstract 674: HPV16 was the preponderant type of HPV infection in cutaneous squamous cell carcinoma

Abstract Purpose: Human papillomavirus (HPV) has been well established as a causative factor in mucosal oropharyngeal cancer and anogenital surface malignancies. However, its etiological role in cutaneous squamous cell carcinoma (cSCC) is still debated. The aim of this study is to identify the presence of HPV types in cSCC and identify their associations with cSCC. Methods: 77 cSCC blocks from 54 patients underwent DNA isolation and a broad spectrum of HPV PCR tests to detect the presence of HPV genotypes by the use of a universal primer pair GP5+/GP6+. The resultant PCR products were cloned to T Vectors and subsequently underwent DNA sequencing and Nucleotide BLAST search to identify the HPV types in cSCC. To ensure the accuracy of the HPV PCR test, 16 blocks from 10 head and neck SCC (oropharyngeal) patients were also included in the HPV presence and type analyses. Cutaneous SCC patients’ demographics, pathology and clinical parameters were compared and analyzed statistically in conjunction with the HPV test results. Results: HPV DNA was found in 37 of 77 (48.1%) blocks representing 32 of 54 (59.3%) cSCC patients. HPV16 was the preponderant type of HPV Infection, accounting for 28 of 32 (87.5%) and 30 of 37 (81.08%) HPV positive patients and blocks. Other HPV genotypes found included HPV18, 57, 10, 2, accounting for 4 of 32 (12.5%), 2 of 32 (6.25%), 2 of 32 (6.25%), 2 of 32 (6.25%) of the HPV positive patients and 4 of 37 (10.81%), 2 of 37 (5.41%), 2 of 37 (5.41%), 2 of 37 (5.41%) of the HPV positive blocks, respectively. HPV infection was significantly associated with the cSCC tumor size in this cohort of patients. Tumors with a size of ≤20mm were more frequently associated with HPV. Moreover, the average tumor size of the HPV positive group was also significantly smaller than that of the HPV negative group. Conclusions: HPV infection is very commonly found in cSCC patients and HPV16 is the major type of HPV involved in cSCC oncogenesis, accounting for &amp;gt;80% of HPV infections. HPV is a contributing factor, which appears to be contributing to a smaller size of cSCC, which may improve the prognostic classification of patients to provide a new insight into tumorigenesis. Citation Format: Gang Shi, Anne C. Fischer, Jonathan M. Zenilman, Patti E. Gravitt, Max Fischer, Inbal B. Sander, Jonathan D. Cuda, Janis M. Taube, Mohammed Lilo, W P Andrew Lee, Anthony P. Tufaro. HPV16 was the preponderant type of HPV infection in cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 674. doi:10.1158/1538-7445.AM2017-674

A single-tube flow cytometric procedure for enhancing the diagnosis and prognostic classification of patients with myelodysplastic syndromes.

We created a simple and effective flow cytometry scoring system (FCSS) for suspected Myelodysplastic syndromes (MDS) samples and evaluated its diagnostic and prognostic potential. Besides evaluating the four parameters suggested by Ogata, we investigated erythroid precursors and mast cells. We evaluated the six-parameter FCSS in a four-color setting (test cohort: 51 patients; 25 controls), then we implemented it into an eight-color setting and tested it on a validation cohort of patients with MDS (n=31). When we compared MDS cases to non-MDS samples in the test cohort, we detected significant differences regarding not only the four major parameters but also two additional ones, namely CD71 rCV% of erythroid precursors (P=.004) and mast cell percentage (MC%) (P=.001). The utilization of the modified six-parameter FCSS provided high sensitivity and specificity both in the four color (84% and 80%, respectively) and in the eight color (81% and 100%, respectively) setting, with an excellent discriminative power between MDS and non-MDS samples. Furthermore, we found significant difference in event-free survival between the risk groups based on the modified six-parameter FCSS (P=.001). We evaluated and validated a single-tube flow cytometric procedure for a simple six-parameter FCSS which has not only high diagnostic but also prognostic power.

Significance of blood neutrophil-to-lymphocyte ratio for prognostic stratification of patients with gastroesophageal junction adenocarcinoma in the era of the 8th edition of the American Joint Committee on Cancer (AJCC8) staging.

The prognosis of patients with gastroesophageal junction (GOJ) adenocarcinoma depends mainly on the clinical staging, as described by the new AJCC8 (American Joint Committee on Cancer 8th edition). Evidence suggests that peripheral blood neutrophil-to-lymphocyte ratio (NLR) may be of prognostic significance in patients with upper gastrointestinal cancers. We examined the prognostic significance of NLR in the era of the new AJCC8 staging system. In this single-centre cohort study, retrospective data on patients with operable GOJ adenocarcinoma treated with perioperative chemotherapy were analysed. The prognostic significance of baseline NLR in combination with AJCC8 clinical staging and other patient characteristics was examined for both time-to-progression (TTP) and overall survival (OS). Of 316 patients, 245 (77.5%) underwent radical surgery. Fifty-one patients (16.2%) developed unresectable disease due to early disease progression. NLR was the only baseline factor independently associated with the development of early disease progression. AJCC8 clinical staging was significantly associated with TTP and OS. In addition, NLR≥3 was predictive of poorer TTP (p=0.001) and OS (p=0.002), confirmed in multivariate Cox-regression analysis. NLR≥3 was prognostic, especially in patients with clinical stage III for TTP (p=0.006) and OS (p=0.025) and in patients with clinical stage IVA for OS (p=0.017). NLR significantly improved the prognostic classification of patients by different AJCC8 clinical stages, with a c-index improved from 0.554 to 0.592 (p<0.001). NLR was confirmed to be an independent prognostic factor in this cohort and could be used in combination with AJCC8 clinical staging to improve the baseline prognostic stratification of patients with newly diagnosed resectable GOJ adenocarcinoma.

Prognostic significance of preoperative plasma fibrinogen and Albumin Score in esophageal cancer patients.

36 Background: The clinical outcome of esophageal cancer has recently improved. However, the relapse rate in any stages is still high. Prognostic classification in patients with esophageal cancer has not yet established. If the patients with poor prognosis could be extracted before surgery, we can add more intensive preoperative treatment, which might lead more favorable prognosis. We have previously reported clinical utility of fibrinogen (FNG) and Albumin (Alb) Score (FA score) in esophageal cancer. The purpose of this study was to analyze the utility of FA score comparing at each stage as a prognostic factor in esophageal cancer. Methods: Patient characteristics, clinicopathological factors, and preoperative biochemical markers (FNG, Alb, and CRP) were investigated in esophageal cancer patients who underwent transthoracic esophagectomy between January 2004 and November 2013. Correlation between preoperative FNG, CRP, Alb, clnicopathological factors and survival were investigated. We evaluated between recurrence-free survival (RFS), overall survival (OS) and FA score comparing at each stage. The cut-off value was defined according to previous reports; fibrinogen 350mg/dl, albumin 3.8mg/dl. Results: 252 patients were recorded. High FA score were correlated to worse OS and RFS (p &lt; 0.001). Especially in cStageI, high FA score showed remarkably worse 5-year RFS (score0/ score1/ score2, 5-year RFS 84%/ 64%/ 33%; p = 0.038). Conclusions: FA score was significantly associated with postoperative survival in esophageal cancer patients. If the patients with poor prognosis in cStageI could be extracted before surgery, we can add more intensive preoperative treatment, which might lead more favorable prognosis.

Clinicopathological significance of SPC18 in colorectal cancer: SPC18 participates in tumor progression.

Colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide. In order to identify novel prognostic markers or therapeutic targets for CRC, we searched for candidate genes in our comprehensive gene expression libraries, and focused on SEC11A, which encodes the SPC18 protein. SPC18 plays a key role in the endoplasmic reticulum‐Golgi secretory pathway and presumably regulates the secretion of various secretory proteins. An immunohistochemical analysis of SPC18 in 137 CRC tissue samples demonstrated that 79 (58%) CRC cases were positive for SPC18. SPC18‐positive CRC cases were more advanced in terms of N classification (P = 0.0315) and tumor stage (P = 0.0240) than SPC18‐negative CRC cases. Furthermore, the expression of SPC18 was an independent prognostic classifier for CRC patients. The cell growth and invasiveness of SPC18 siRNA‐transfected CRC cell lines was less than that of the negative control siRNA‐transfected cell lines. The levels of phosphorylated epidermal growth factor receptor, Erk and Akt were lower in SPC18 siRNA‐transfected CRC cells than in control cells. The expression of SPC18 was colocalized with β‐catenin nuclear localization and MMP7 at the invasive front. An immunohistochemical analysis of human colorectal polyp specimens revealed a sequential increase in the expression of SPC18 through the conventional adenoma‐carcinoma pathway, while SPC18 was not expressed or was expressed to a lesser extent in serrated pathway‐related tumors. These results suggest that SPC18 is involved in tumor progression, and is an independent prognostic classifier in patients with CRC.

The potential of optimizing prehospital triage of patients with suspected acute myocardial infarction using high-sensitivity cardiac troponin T and copeptin

Purpose: In patients with a suspected acute myocardial infarction (AMI), to evaluate the potential for early triage based on measurement of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin in blood samples collected in the prehospital phase.Materials and methods: In this retrospective study, we measured hs-cTnT and copeptin in blood samples collected in the ambulance form 962 patients with suspected AMI. The diagnostic accuracy was estimated by receiver-operating characteristic (ROC) curve area under the curve (AUC) for both biomarkers and a combined model. Multivariable Cox regression modelling was used to estimate the predictive value of both biomarkers.Results: In total, 178 (19%) cases had AMI. The AUC for hs-cTnT was 0.81. Adding copeptin increased the AUC to 0.85 (p = 0.004) and the combined model allowed a prehospital rule-out of 45% of cases without AMI (negative predictive value, NPV 98%). Both biomarkers are highly predictive of outcome.Conclusions: A future application of hs-cTnT and copeptin measurement, performed already in the prehospital phase, could potentially improve the prehospital diagnostic and prognostic classification of patients with a suspected AMI.

Prognostic and predictive values of diffusion and perfusion MRI in paediatric intracranial ependymomas in a large national study.

To assess the relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) derived, respectively, from perfusion and diffusion pre-operative MRI of intracranial ependymomas and their predictive and prognostic values. Pre-operative MRI and clinical data for intracranial ependymomas diagnosed between January 2000 and December 2013 were retrospectively retrieved from a web-based national database. MRI data included diffusion (62 patients) and perfusion (20 patients) MRI. Patient age, histopathological diagnosis, tumour location, ADC, relative ADC (rADC) and rCBV were considered as potential factors in a survival analysis. Survival rates were estimated using the Kaplan-Meier method. Univariate analyses were performed using the log-rank test to compare groups. We also performed a multivariate analysis, applying the Cox proportional hazards model. ADC and rADC values within hypointense regions differed significantly between grades II and III (p = 0.01). The 75th percentile of ADC within hypointense regions and the 25th percentile of rCBV within non-enhancing lesions were prognostic of disease-free survival (p = 0.004, p = 0.05). A significant correlation was found between the 75th percentile of rCBV and the 25th percentile of rADC (p = 0.01) in enhancing regions of grade-III tumours. Pre-operative rADC and rCBV could be used as prognostic factors for clinical outcome and to predict histological grade in paediatric ependymomas. Prognostic value of diffusion and perfusion MRI in paediatric ependymoma was found and may play a role in the prognostic classification of patients in order to design more tailored treatment strategies.