Predictor Of Poor Overall Survival Research Articles

Prognostic Significance of Bcl-2 and Bcl-6 Immunostaining in B-Cell Non-Hodgkin's Lymphoma

Purpose: The aim of this study was to identify a possible effect of Bcl-2 and Bcl-6 proteins on the clinical behavior and outcome in different subtypes of B-cell non-Hodgkin lymphoma (B-NHL). Methods: We retrospectively studied Bcl-2 and Bcl-6 expression by immunohistochemistry (IHC) in 145 patients with diffuse large B-cell lymphoma (DLBCL), 86 patients with follicular lymphoma (FL), and 53 patients with mantle cell lymphoma (MCL), and analyzed their prognostic relevance and effect on treatment response in these cohorts. Results: Positive Bcl-2 expression related strongly to lower rates of complete response (CR) after first-line treatment with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in both DLBCL (p=0.001) and MCL (p=0.01). Bcl-2 was recognized as an independent predictor of poor overall survival (OS) (HR=2.9, p<0.001, and HR=3.7, p= 0.02 in DLBCL and MCL, respectively). Patients with positive expression of Bcl-6 were more likely to achieve CR after R-CHOP in both DLBCL (p=0.006) and FL (p=0.012). Bcl-6 positive expression was an independent indicator of a favorable OS (HR=0.3, p<0.001, and HR=0.4, p=0.04 in DLBCL and FL, respectively). An IHC score based on the expression of Bcl-2 and Bcl-6 in DLBCL accurately defined three risk groups with markedly different OS (p<0.001). This new score outweighed the International Prognostic Index (IPI) as a prognostic indicator (HR=3.2 vs 2.2, p<0.001). Conclusion: Bcl-2 and Bcl-6 protein expression detected by IHC can be reliably used to help predict treatment response and survival trends in a wide subset of B-NHLs. Funding Information: None to declare. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This study was approved by the local ethics committee.

Clinical Significance of Chemokine Receptor CXCR4 and CCR7 mRNA Expression in Patients With Colorectal Cancer.

The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.

Prognostic Value of Glucose-to-Lymphocyte Ratio in Critically Ill Patients with Acute Pancreatitis.

BackgroundGlucose metabolism and systemic inflammation have been associated with prognosis in acute pancreatitis (AP) patients. However, the possible value as a prognostic marker of the glucose-to-lymphocyte ratio (GLR) has not been evaluated in critically ill patients with AP.MethodsThis study included 1,133 critically ill patients with AP from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, who were randomly divided into the training cohort (n=806) and the validation cohort (n=327) at a ratio of 7:3. X-tile software was used to determine the optimal cut-off values for GLR. Area under the curve (AUC) analysis was performed to compare the performance between GLR and other blood-based inflammatory biomarkers. Univariate and multivariate Cox regression analyses were applied to select prognostic factors associated with in-hospital mortality. A nomogram model was developed based on the identified prognostic factors and the validation cohort was used to further validate the nomogram.ResultsThe optimal cut-off value for GLR was 0.9. The ROC analyses showed that the discrimination abilities of GLR were better than other blood-based inflammatory biomarkers. Multivariate Cox regression analysis demonstrated that age, platelet, albumin, bilirubin, Sequential Organ Failure Assessment (SOFA) score, and GLR are independent predictors of poor overall survival in the training cohort and were incorporated into the nomogram for in-hospital mortality as independent factors. The nomogram exhibited better discrimination with C-indexes in the training cohort and the validation cohort of 0.886 (95% CI=0.849–0.922) and 0.841 (95% CI=0.767–0.915), respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of in-hospital mortality in both sets.ConclusionAs an easily available biomarker, GLR can independently predict the in-hospital mortality of critically ill patients with AP. The nomogram combining GLR with other significant features exerted favorable predictive performance for in-hospital mortality.

PD37-01 LOSS OF FOXA1 RESULTS IN GENOME-WIDE EPIGENETIC REPROGRAMMING AND ACTIVATION OF INTERFERON-RESPONSE GENES INCLUDING CD274 /PD-L1

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (PD37)1 Sep 2021PD37-01 LOSS OF FOXA1 RESULTS IN GENOME-WIDE EPIGENETIC REPROGRAMMING AND ACTIVATION OF INTERFERON-RESPONSE GENES INCLUDING CD274/PD-L1 Hironobu Yamashita, Wenhuo Hu, Joshua Warrick, Vonn Walter, Jenna Craig, Hikmat Al-Ahmadie, and David Degraff Hironobu YamashitaHironobu Yamashita More articles by this author , Wenhuo HuWenhuo Hu More articles by this author , Joshua WarrickJoshua Warrick More articles by this author , Vonn WalterVonn Walter More articles by this author , Jenna CraigJenna Craig More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , and David DegraffDavid Degraff More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002047.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Forkhead Box A1 (FOXA1) is a pioneer transcription factor (TF) critical in epigenetic regulation of chromatin state and cell fate determination. Reduced FOXA1 is an independent predictor of poor overall survival in bladder cancer (BC) patients. However, the impact of FOXA1 loss on chromatin epigenetics in BC is unknown. Therefore, we determined the impact of FOXA1 KO on epigenetic modification of chromatin and associated gene expression. Our integrated analysis identifies FOXA1 as an important regulator of chromatin epigenetic state and expression of immune checkpoint (IC) targets in BC. METHODS: We used CRISPR/Cas9 to delete FOXA1 in the human luminal BC cells. We performed RNA-seq and Chip-seq for H3K27ac, an epigenetic mark of active enhancers/promoters. Motif and GSEA analysis of RNA/Chip-seq were performed to identify FOXA1 KO-induced epigenetic differences influencing gene expression. Western blotting (WB)/qPCR confirmed FOXA1-mediated CD274/PD-L1 expression. In silico analysis of TCGA data also confirmed relevance to human disease. RESULTS: We identified 8,230 differentially expressed genes in FOXA1 KO. Notably, GSEA identified IFNɑ/ɣ gene signatures as enriched in FOXA1 KO. As expected, the majority of differences in H3K27ac across genomic areas in FOXA1 KO were mapped to intergenic (n=6,250 peaks; 42% of total peaks) and intronic (n=6,490; 43%) regions. In addition, differential H3K27ac levels were also mapped to proximal promoters (n=1,306; 9%) as well as within gene bodies (n=931; 6%). Integrated analysis of RNA/ChIP-seq shows changes in gene expression are mirrored by differences in H3K27ac. Motif analysis of DNA sequence enriched for H3K27ac identified significant increases in TF binding motifs including the interferon (IFN) sensitive response element (ISRE) and IFN response factors such as IRF1. Moreover, we identified increased H3K27ac of regulatory elements as being associated with several upregulated ISGs in FOXA1 KO. These include ISG15, IFIT2/3, IFI44L and CD274/PD-L1. WB/qPCR confirmed upregulation of several ISGs, including CD274/PD-L1 following FOXA1 KO. Analysis of TCGA data confirmed an inverse relationship between FOXA1 and CD274 in BC and other cancers. CONCLUSIONS: In summary, we provide evidence of widespread epigenetic reprogramming after FOXA1 KO in BC cells. Additionally, we provide evidence that epigenetic changes contribute to activation of a global IFN-dominant signature, including CD274/PD-L1 in a cancer cell-intrinsic manner in FOXA1 KO. Source of Funding: Supported in part by RSG 17-233–01-TBE from the American Cancer Society (D.J.D.), The W.W. Smith Charitable Trust (D.J.D.), the Ruth Heisey Cagnoli Endowment in Urology at Penn State College of Medicine and the Bladder Cancer Support Group at Penn State Health © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e655-e655 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hironobu Yamashita More articles by this author Wenhuo Hu More articles by this author Joshua Warrick More articles by this author Vonn Walter More articles by this author Jenna Craig More articles by this author Hikmat Al-Ahmadie More articles by this author David Degraff More articles by this author Expand All Advertisement Loading ...

Validating HMMR Expression and Its Prognostic Significance in Lung Adenocarcinoma Based on Data Mining and Bioinformatics Methods.

Hyaluronic acid-mediated motility receptor (HMMR), a tumor-related gene, plays a vital role in the occurrence and progression of various cancers. This research is aimed to reveal the effect of HMMR in lung adenocarcinoma (LUAD). We first obtained the gene expression profiles and clinical data of patients with LUAD from The Cancer Genome Atlas (TCGA) database. Then, based on the TCGA cohort, the HMMR expression difference between LUAD tissues and nontumor tissues was detected and verified with public tissue microarrays (TMAs), clinical LUAD specimen cohort, and Gene Expression Omnibus (GEO) cohort. Logistic regression analysis and chi-square test were adopted to study the correlation between HMMR expression and clinicopathological parameters. The effect of HMMR expression on survival was evaluated by Kaplan–Meier survival analysis and using the Cox regression model. Furthermore, Gene Set Enrichment Analysis (GSEA) was utilized to screen out signaling pathways related to LUAD and the co-expression analysis was employed to build the protein–protein interaction (PPI) network. The HMMR expression level in LUAD tissues was dramatically higher than that in nontumor tissues. Logistic regression analysis and chi-square test demonstrated that the high HMMR expression in LUAD has relation with gender, pathological stage, T classification, lymph node metastasis, and distant metastasis. The Kaplan–Meier curve suggested a poor prognosis for LUAD patients with high HMMR expression. Multivariate analysis implied that the high HMMR expression was a vital independent predictor of poor overall survival (OS). GSEA indicated that a total of 15 signaling pathways were enriched in samples with the high HMMR expression phenotype. The PPI network gave 10 genes co-expressed with HMMR. HMMR may be an oncogene in LUAD and is expected to become a potential prognostic indicator and therapeutic target for LUAD.

SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia.

Background: Acute myeloid leukemia (AML), characterized by the low cure rate and high relapse, urgently needs novel diagnostic or prognostic biomarkers and potential therapeutic targets. Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) is a negative regulator of Toll-like receptor signaling that plays important roles in the interface of membrane biology and innate immunity. However, the potential role of SMPDL3B in human cancer, especially in AML, is still unknown.Methods: The expression of SMPDL3B in AML samples was investigated through data collected from Gene Expression Omnibus (GEO). Association between SMPDL3B expression and clinicopathologic characteristics was analyzed with the chi-square test. Survival curves were calculated by the Kaplan–Meier method. Cox univariate and multivariate analyses were used to detect risk factors for overall survival. The biological functions of SMPDL3B in human AML were investigated both in vitro and in vivo.Results: Expression of SMPDL3B mRNA was significantly upregulated in human AML samples and closely correlated to cytogenetics risk and karyotypes. Elevated expression of SMPDL3B was associated with poor overall survival and emerged as an independent predictor for poor overall survival in human AML. Blocked SMPDL3B expression inhibited AML cells growth both in vitro and in vivo via promoting cell apoptosis.Conclusion: Taken together, our results demonstrate that SMPDL3B could be used as an efficient prognostic biomarker and represent a potential therapeutic target for human AML.

Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis.

To determine how MRI features are correlated to biomarkers, and to the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients. The study enrolled 160 cHCC-CCA patients pathologically confirmed according to the 2019 WHO classification. The preoperative MRI features and clinical data were retrospectively evaluated and compared between patients grouped by AFP or CA19-9 level and with pathological findings. The RFS and OS of cHCC-CCA patients were estimated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, predictors of RFS and OS were investigated using Cox regression analyses. One hundred and sixty patients (mean age, males vs. females: 55.7 ± 10.2 years vs. 54.9 ± 14.0 years) were evaluated. The incidence of nodule-in-nodule architecture, mosaic architecture, intratumoral hemorrhage, hepatic capsule retraction, arterial phase peritumoral enhancement, and portal vein thrombus was significantly higher in patients with AFP > 20 ng/ml (all p < 0.05). Multivariate Cox regression analysis indicated that age (HR 1.031, p = 0.03), CA19-9 > 37 U/ml (HR 1.880, p = 0.04), arterial phase peritumoral enhancement (HR 2.287, p = 0.01), and delayed enhancement (HR 0.377, p = 0.02) were independent predictors of poor RFS, while arterial phase peripheral enhancement (HR 2.391, p = 0.04) was an independent predictor of poor OS. cHCC-CCA imaging features are complex and not correlated with AFP or CA19-9. Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor RFS. Arterial phase peripheral enhancement is an independent predictor of poor OS. • The imaging features of combined hepatocellular carcinoma-cholangiocarcinoma are complex and are not correlated with the alpha fetoprotein or CA19-9 levels. • Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor recurrence-free survival in combined hepatocellular carcinoma-cholangiocarcinoma patients. • Arterial phase peripheral enhancement is an independent predictor of poor overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma.

Pretreatment Nutrition-Inflammation Biomarkers Correlated with Differential Cytokine Profiles in Taiwanese Patients with Colorectal Cancer

Systemic inflammation plays a pivotal role in colorectal cancer (CRC) development. Two hallmarks reflect the severity of inflammation—circulating cytokines and nutrition-inflammation biomarkers (NIBs); however, their interplay has not been fully investigated. In total, 128 CRC patients were included. Ten circulating cytokines (TNF-α, TGF-β, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) and NIBs were analyzed. The relationship between cytokines, NIBs, clinicopathological variables, and overall survival (OS) was assessed using univariate and multivariate analyses. Three NIBs (CRP-to-albumin ratio [CAR]), neutrophil-to-lymphocyte ratio [NLR]), and prognostic nutritional index [PNI]) were associated with OS in univariate analysis; however, CAR was better for OS prediction in multivariate analysis (P = 0.015). None of the serum cytokines analyzed showed a significant association with OS. High CAR (≥0.25) and high IL-10 (≥76.6 pg/mL), high NLR (≥8.2) and high IL-23 (≥51.2 pg/mL), and high PNI (≥42.4) and high IL-1β (≥14.3 pg/mL) values were correlated. CAR, NLR, and PNI were not correlated with each other, whereas circulating cytokines were closely interrelated. High CAR was an independent predictor of poor OS in patients with CRC. Different NIBs have unique cytokine profiles, but show no correlation with each other. There is a close association among the circulating cytokines.

Impact of skin invasion on long-term survival outcomes in gingivobuccal complex carcinoma

IntroductionGingivo-buccal complex cancers (GBCC) have an aggressive clinical course in the presence of skin and bone involvement. ObjectiveThis study intends to analyze the clinico-pathological factors affecting local control and survival outcomes in GBCC. MethodsThis is a retrospective study conducted on 125 GBCC cases from January 2011 to April 2016. ResultUnivariate analysis revealed lymphovascular invasion (LVI) and skin involvement as predictors of poor overall survival (OS) and disease- free survival (DFS). Multivariate analysis showed skin involvement and LVI to be independent prognostic factors towards poor OS. Corresponding results in case of DFS showed skin involvement to be the single most important prognostic factor. With a median follow up of 24 months, the median survival of patients with skin involvement, skin and mandible invasion and isolated mandible invasion, respectively, were 18 months, 12 months and 22 months. ConclusionGBCC with skin involvement portends poor outcome in terms of survival. In the presence of skin invasion, treatment entails liberal soft tissue and bone margin followed by adjuvant treatment.

Clinical features of patients with pancreatic ductal adenocarcinoma with a history of other primary malignancies: A retrospective analysis.

Patients with pancreatic ductal adenocarcinoma (PDAC) that have a history of other primary malignancies are not well documented. The current study therefore aimed to evaluate the clinicopathological characteristics of patients with PDAC with or without a history of other primary malignancies. A total of 102 patients with surgically treated PDAC that presented with or without a history of other primary malignancies were retrospectively analyzed. A total of 25 patients (24.5%) had a history of other primary malignancies (age, with history of other primary malignancy vs. without, 74.2 vs. 68.9 years; P=0.005) and the reason for consultation (P<0.001) differed significantly between the groups with a history of other primary malignancies [HoM(+)] and without a history of other primary malignancies [HoM(-)]. Incidental indications during malignancy follow-up was the most common reason for the diagnosis of PDAC in the HoM(+) group. Conversely, there were no significant differences in the resectability (P=0.645), complete resection rate (P=0.774) and final stage (P=0.474) between the two groups. Disease-free survival was also not significantly different between the two groups (P=0.184). However, overall survival was significantly poorer in the HoM(+) group compared with the HoM(-) group (P=0.003). A history of other primary malignancies was also an independent predictor of poor overall survival (hazard ratio, 2.416; 95% confidence interval, 1.324-4.406; P=0.004). In conclusion, patients with PDAC and a history of other primary malignancies had significantly poorer overall survival than their counterparts, despite no differences in disease-free survival.

Prognostic Factors and Survival Outcomes in Phase I Patients with Hematologic Malignancies

Introduction: Patient selection is a challenge in designing effective phase I clinical trials in hematologic malignancies. Potential candidates typically have relapsed or refractory disease, and have had poor response to multiple prior lines of therapy. Such patients are at risk for early death, which reduces both the scientific yield and the therapeutic value of clinical trials: patients whose disease has already entered a terminal phase, and who subsequently die within a few months, provide little meaningful data to advance the understanding of an experimental treatment, and likely derive little clinical benefit from that treatment.Currently, eligibility criteria for most trials rely on ad hoc laboratory thresholds, and on subjective assessments of performance status and life expectancy. It is desirable to have an objective, statistically validated means of predicting survival, to optimize patient selection for phase I clinical trials. A prognostic scoring system for this purpose has been developed and validated for patients with solid tumors (Garrido-Laguna et al. Cancer . 2012;118(5):1422-1428); this model incorporates variables on tumor type and number of metastatic sites, which are not directly applicable outside of solid tumors. Similar work has recently been reported in hematologic malignancies (Benajiba et al. Anti-cancer drugs . 2017;28(5):540-545), using only three variables: performance status, serum albumin, and disease class. We developed a novel prognostic scoring system to estimate progression free (PFS) and overall (OS) survival for patients enrolled in phase I clinical trials for treatment of hematologic malignancy.Methods: We retrospectively reviewed the electronic medical records of 106 patients enrolled in phase I clinical trials for treatment of hematologic malignancies at the UT Health San Antonio Cancer Center between 2000 and 2014. Descriptive, univariate, and multivariate analyses were performed to determine the parameters that carry prognostic significance. Cox proportional hazards regression models of Progression Free and Overall Survival (PFS, OS) were used for multivariate analyses. A backward elimination process with a relaxed P-value (0.2) threshold was used to select variables for adjustment.Results: Our analysis identified Hispanic ethnicity (P=0.03), low albumin level (<3.5 g/dL), low hemoglobin (<10 g/dL, P=0.02), hyperbilirubinemia (>1.0 mg/dL, P=0.03), abnormal white blood cell count (<4 k/µL or >10 k/µL, P<0.01), elevated lactate dehydrogenase (LDH) (>240 IU/L, P<0.01), and diagnosis of acute leukemia (P<0.01) as independent predictors of poor overall survival. The patient cohort was stratified by risk score into good (0-1), intermediate (2-4), and poor (5-7) risk categories, which were compared with respect to PFS and OS using Kaplan-Meier curves and log rank testing (see figures 1 and 2).Conclusion: A simple score incorporating diagnosis, ethnicity, albumin, hemoglobin, bilirubin, white blood count, and LDH can identify patients with advanced hematologic malignancy who are likely to have short OS and PFS. Efforts are underway to validate this score against a separate cohort of phase I patients. Once validated, it could be incorporated in phase I trial design, potentially making these trials easier, faster, and more cost-effective to conduct, while allocating experimental treatments to those patients most likely to derive benefit. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Transplant Still Relevant Even in the Era of Novel Treatments for Multiple Myeloma — National Cancer Database Analysis

Background: Survival of patients with multiple myeloma has significantly improved over the last decade. Several new treatments have been approved for the treatment of myeloma in the last few years that have changed its landscape. Newer drugs with deeper and durable responses have challenged the role of autologous stem cell transplant (auto SCT) in the management of myeloma.Aim: We aimed to study the impact of auto SCT and several other demographic and treatment related factors on the outcome of myeloma by analyzing the data from National Cancer Database (NCDB).Materials and Methods: Data was analyzed from 9218 patients (both men and women aged >18 years) who were diagnosed with multiple myeloma and registered in NCDB between 2010 and 2013 with follow up to the end of 2014. Factors such as age, race, gender, income, education, Charlson comorbidity index (CCI), distance traveled to get cancer care, treatment facility, health insurance and type of treatment (chemotherapy only versus chemotherapy followed by auto SCT) were investigated and the primary outcome was overall survival.Results: The median age of the patients was 66 years. Fifty five percent of patients were male. Around 56% of the patients were older than 65 years. Among the patients reviewed, 73% were Caucasian and 24% African American. As assessed by Charlson comorbidity index, 75% of patients had no major medical comorbidities. Forty six percent of patients received treatment at a facility different from where they were diagnosed with myeloma. Around one third of the patients were treated at an academic facility and the rest at either a community cancer program or comprehensive community cancer program. Treatment was initiated within 2 weeks of diagnosis in 36% of the patients whereas 21% of patients could not start treatment until after 6 weeks from diagnosis. Approximately 53% of patients had health care funding by Medicare, 35% had private insurance, 7% had Medicaid and around 5% of the patients were uninsured. Around 11% of the patients received auto SCT as part of treatment. In a multivariate analysis, after adjusting for other variables, receiving auto SCT was a statistically significant predictor of overall survival. A 71% improvement in survival was observed in patients who received auto SCT for myeloma compared to those who did not. Male gender, age older than 65 years, African American race, major comorbidities as determined by CCI, change of facility for treatment were other significant predictors of survival in the multivariate analysis. Females were 11% less likely to die of myeloma compared to males. Patients older than 65 years had 59% increased risk of dying compared to patients younger than 40 years. African Americans had 17% reduced risk of death compared to Caucasians. Myeloma patients with 1 and 2 medical comorbidities had 31% and 75% increased risk of death respectively compared to those with no comorbidities. Receiving treatment at a facility different from that of diagnosis had a very small survival advantage. Patients with Medicaid, Medicare and no health insurance had 16%, 29% and 19% increased risk of death compared to those with private insurance respectively. Level of education of patients, annual income and distance traveled to the treatment facility did not have any significant impact on the overall survival in multivariate analysis.Conclusions: Even in the era of novel drugs for the treatment of myeloma, auto SCT still has a significant role and offers overall survival benefit according to our NCDB analysis. Male gender, elderly age, 1 or more medical comorbidities, lack of private health insurance were shown to be predictors of poor overall survival. DisclosuresNo relevant conflicts of interest to declare.

Transferrin predicts outcome in patients who underwent liver resection for colorectal liver metastases.

The aim of this study is to investigate the relationship between preoperative serum transferrin level and long-term outcomes in patients with colorectal liver metastases after hepatic resection. We retrospectively investigated 72 patients who underwent hepatic resection for colorectal liver metastases and explored the relationship between serum transferrin level and long-term outcomes. In multivariate analysis, H3 (odds ratio 3.43, 95% confidence interval 1.11-10.89 and P=0.03) was an independent and significant predictor of the disease-free survival, and a transferrin level≥190mg/dl (odds ratio 0.20, 95% confidence interval 0.05-0.79 and P=0.02) and the time to recurrence after hepatectomy <1year (odds ratio 11.30, 95% confidence interval 2.63-48.59 and P<0.01) were independent and significant predictors of the overall survival. The serum transferrin level is a useful predictor of poor overall survival in patients with colorectal liver metastases after hepatic reaction.

Preoperative plasma D-dimer independently predicts survival in patients with pancreatic ductal adenocarcinoma undergoing radical resection

BackgroundElevated plasma D-dimer levels have been reported as an unfavorable prognostic indicator in many solid tumors. However, there are limited relevant studies in pancreatic cancer patients following radical surgery, and the clinical significance remains controversial. The aim of this study was to investigate the clinical and prognostic significance of preoperative plasma D-dimer in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection.MethodsA retrospective analysis was performed on all patients who consecutively underwent radical surgery for PDAC by laparotomy or robotic surgery from December 2011 to December 2018. Baseline clinicopathologic characteristics, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to analyze the prognostic value of preoperative plasma D-dimer.ResultsAmong 1351 patients, elevated preoperative plasma D-dimer levels (≥ 0.55 ng/mL) were found in 417 (30.9%) patients. Three hundred twelve (23.09%) underwent minimally invasive robotic pancreatectomy. The median overall survival (OS) of patients with elevated D-dimer levels was 6.3 months shorter than that of patients with normal D-dimer levels (15.0 months vs 21.3 months, p < 0.001). Multivariate analysis showed that elevated D-dimer levels independently predicted poorer OS (hazard ratio, 1.33; 95% confidence interval, 1.17-1.51, p < 0.001). Subgroup analysis demonstrated that D-dimer was a reliable prognostic factor in patients who underwent R0 resection. In addition, integration of D-dimer, carbohydrate antigen 19-9 (CA19-9), and NLR provided a better prognostic model for PDAC patients before operation.ConclusionAn elevated preoperative plasma D-dimer level was a reliable independent prognostic factor for OS in patients with PDAC undergoing resection. Combination of D-dimer, CA19-9, and NLR can enhance the prognostic accuracy before operation.

High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma.

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues (p < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all p < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all p < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor (p < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all p < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.

Dynein Light Chain Protein Tctex1: A Novel Prognostic Marker and Molecular Mediator in Glioblastoma.

Simple SummaryGlioblastoma (GBM) remains one of the deadliest solid cancers, with only a dismal proportion of GBM patients achieving 5-year survival. Thus, it is critical to identify molecular mechanisms that could be targeted by novel therapeutic approaches in this tumor type. Our study identified Tctex1/DYNLT1 as an independent prognostic marker for the overall survival of GBM patients. Importantly, Tctex1 promoted the aggressiveness of GBM cells by enhancing tumor proliferation and invasion. These effects of Tctex1 appeared to be modulated via phosphorylation of retinoblastoma protein (RB) and the release of matrix metalloprotease 2 (MMP2), respectively. As Tctex1 can potentially be inhibited in vivo, our study provides a rationale for novel, individualized therapeutic strategies in GBM patients.The purpose of this study was to determine the role of Tctex1 (DYNLT1, dynein light chain-1) in the pathophysiology of glioblastoma (GBM). To this end, we performed immunohistochemical analyses on tissues from GBM patients (n = 202). Tctex1 was additionally overexpressed in two different GBM cell lines, which were then evaluated in regard to their proliferative and invasive properties. We found that Tctex1 levels were significantly higher in GBM compared to healthy adjacent brain tissues. Furthermore, high Tctex1 expression was significantly associated with the short overall- (p = 0.002, log-rank) and progression-free (p = 0.028, log-rank) survival of GBM patients and was an independent predictor of poor overall survival in multivariate Cox-regression models. In vitro, Tctex1 promoted the metabolic activity, anchorage-independent growth and proliferation of GBM cells. This phenomenon was previously shown to occur via the phosphorylation of retinoblastoma protein (phospho-RB). Here, we found a direct and significant correlation between the levels of Tctex1 and phospho-RB (Ser807/801) in tissues from GBM patients (p = 0.007, Rho = 0.284, Spearman’s rank). Finally, Tctex1 enhanced the invasiveness of GBM cells and the release of pro-invasive matrix metalloprotease 2 (MMP2). These findings indicate that Tctex1 promotes GBM progression and therefore might be a useful therapeutic target in this type of cancer.

Myostatin as a fibroblast-activating factor impacts on postoperative outcome in patients with hepatocellular carcinoma.

In patients with liver cirrhosis, high levels of serum myostatin are associated with poor prognosis. We aimed to clarify the influence of myostatin on the prognosis of patients with non-alcoholic fatty liver disease-hepatocellular carcinoma (NAFLD-HCC) without cirrhosis and on the progression of liver fibrosis. Serum myostatin levels were evaluated in 234 patients who underwent primary surgical resection for single HCC. To clarify the impact of myostatin on liver fibrosis, we established human primary liver fibroblasts from resected livers, and cultured them in the presence of myostatin. The median age was 67.4years, the median L3 skeletal muscle mass index was 44.4cm2 /m2 , and the median body mass index was 23.4kg/m2 . Eighty-two (35.0%) patients had sarcopenia (L3 skeletal muscle mass index: men <42, women <38cm2 /m2 ). The etiologies of liver disease were hepatitis B virus (n=61), hepatitis C virus (n=86), and non-B non-C hepatitis (n=87) including NAFLD (n=74). High preoperative serum myostatin and vascular invasion were independent predictors of poor overall survival (OS). High serum myostatin was associated with poor OS in patients with no sarcopenia (n=152). In patients without advanced liver fibrosis (Fibrosis stage, 0-2; n=58), high levels of serum myostatin were also associated with poor OS, regardless of sarcopenia. Serum myostatin levels were increased with the progression of liver fibrosis. Liver fibroblasts were activated and produced collagen following stimulation with myostatin. In patients with NAFLD-HCC without advanced liver fibrosis, high levels of serum myostatin were associated with poor OS. Myostatin activated primary fibroblasts and stimulated collagen production.

Combined bone scintigraphy and fluorocholine PET/computed tomography predicts response to radium-223 therapy in patients with prostate cancer.

Aim:To assess the value of bone scintigraphy and 18F-fluorocholine PET/computed tomography (CT) in predicting outcome in patients with prostate cancer and bone metastases treated with 223radium.Materials & methods:Retrospective analysis of 48 patients that underwent 223radium therapy. End points were pain relief and overall survival.Results:After therapy, pain relief was observed in 27 patients. Patients without pain relief had more bone lesions at PET/CT than at bone scintigraphy (pretherapy imaging mismatch). In 39 patients who completed treatment protocol, post-therapy alkaline phosphatase and pretherapy imaging mismatch were independent predictors of poor overall survival.Conclusion:Patients with more lesions at 18F-fluorocholine PET/CT than at bone scintigraphy had a poor prognosis. The combined imaging approach could be useful to predict outcome after 223radium therapy.

DIS3 mutations in multiple myeloma impact the transcriptional signature and clinical outcome

DIS3 gene mutations occur in roughly 10% of patients with multiple myeloma (MM); furthermore, DIS3 expression can be affected by monosomy 13 and del(13q), which occur in approximately 40% of MM cases. Despite several reports on the prevalence of DIS3 mutations, their contribution to the pathobiology of MM remains largely unknown. We took advantage of the large public CoMMpass dataset to investigate the spectrum of DIS3 mutations in MM and its impact on the transcriptome and clinical outcome. We found that the clinical relevance of DIS3 mutations strictly depended on the co-occurrence of del(13q). In particular, bi-allelic DIS3 lesions significantly affected progression-free survival, independently of other predictors of poor clinical outcome, while mono-allelic events mostly affected overall survival. As expected, DIS3 mutations affect the MM transcriptome involving cellular processes and signaling pathways associated with RNA metabolism, and the deregulation of a large number of long non-coding RNA, among which we identified five distinct transcripts as independent predictors of poorer overall survival and nine of worse progression-free survival, with two (AC015982.2 and AL445228.3) predicting both unfavorable outcomes. These findings strongly prompt further studies investigating the relevance of these long non-coding RNA in MM.

Patient's age and D-dimer levels predict the prognosis in patients with TAFRO syndrome.

ObjectivesTo identify prognostic factors for TAFRO syndrome, a rare inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly.MethodsData of patients with TAFRO syndrome were extracted from a Japanese patient registry. Patients were divided into groups according to the clinical and laboratory parameters at initial presentation. Cut-off values for the laboratory parameters were determined using receiver operating characteristic curve analysis and by clinical relevance. Patient survival was analyzed by the Kaplan–Meier method. Univariable analysis was performed using log-rank tests. Multivariable analyses were performed with the logistic regression model and the Cox proportional hazards model.ResultsWe extracted the data of 83 patients with TAFRO syndrome from the registry. Univariable analysis identified several potential prognostic factors. Of these factors, age ≥60 years and D-dimer ≥18 μg/dL remained significant predictors of poor overall survival in the multivariable Cox proportional hazards model. Based on these results, we developed a simple prognostic scoring system for TAFRO syndrome (TS-PSS).ConclusionPatients in our cohort were stratified into low, intermediate, and high-risk groups by the TS-PSS. This system should be verified with independent patient cohorts in future studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12185-021-03159-x.