scholarly journals Prognosis of early stage small cell bladder cancer is not always dismal

ESMO Open ◽  
2019 ◽  
Vol 4 (6) ◽  
pp. e000559
Author(s):  
Jun Hao Lim ◽  
Santhanam Sundar
Keyword(s):  
Early Stage ◽  
Survival Outcome ◽  
Small Cell ◽  
Disease Stage ◽  
Rank Test ◽  
P Value ◽  
Early Stage Disease ◽  
Retrospective Audit ◽  
Stage Disease ◽  
Significant Difference

Background Small cell carcinoma of the urinary bladder (SCCB) is an extremely rare malignancy which is often associated with poor survival outcome. Literature reporting such disease is scarce. There is no standardised management. This retrospective audit examines a UK Cancer Centre’s SCCB management and survival outcomes.Methods Histopathology database at Nottingham University Hospitals, UK, was used to identify patients diagnosed with SCCB from January 2008 to January 2016.Results 27 patients had confirmed diagnosis of SCCB. Mean age at diagnosis was 68.7 (range 37–90). 30% of the cases had pure small cell histology, while the rest were mixed histological subtype. Of the 12 patients with early stage disease (stage I and II), three had radical cystectomy and chemotherapy, six had both radiotherapy and chemotherapy, two had either radiotherapy or chemotherapy alone, and one declined active treatment. Of the 12 patients with advanced disease (stage III and IV), four had chemotherapy alone, four had both radiotherapy and chemotherapy and four was for best supportive care. 13 out of 16 patients who had chemotherapy received combination of carboplatin and etoposide. Patients with advanced stage disease had medial survival of 9 months (95% CI 3.9 to 14.1 months). The median survival for patients with early disease was not reached. There is significant difference in survival between early and late stage disease (p value 0.008, Log rank test).Conclusions Our results demonstrated a reasonable survival outcome in early stage SCCB patients. Radical multimodality treatment options should not be precluded in patients with early stage SCCB.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

Expression of the Cancer-Testis Antigens, SEMG 1 and Protamine 1, in Early CLL: Their Relationship to Disease Stage and Zap 70 Expression.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4680-4680
Author(s):  
Farouk Meklat ◽  
Yana Zhang ◽  
Zhiqing Wang ◽  
Jian Zhang ◽  
Sukhrob Mustalov ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Tumor Vaccine ◽  
Early Stage ◽  
Disease Stage ◽  
Early Disease ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Ct Antigen ◽  
Cancer Testis ◽  
Protamine 1

Abstract Despite advances in modern chemotherapy, CLL remains incurable. CLL is an indolent disease. It expresses a panel of Cancer-Testis (CT) antigens. CLL leukemia cells are susceptible to the cytotoxicity of T cells. CLL is, therefore, an ideal disease for immunotherapeutic approaches. Immunotherapy, in addition to being less toxic and more specific than chemotherapy, provides a different mode of cytotoxicity that may synergize with that induced by chemotherapeutic agents. Immunotherapy also offers the prospect of inducing immune memory that may be important for long term disease-free survival of patients with CLL. However, there are obstacles that may prevent successful immunotherapy. CLL patients are generally immunosuppressed even before any therapy is given and the immunosuppression increases as the disease progresses. Therefore, any immunotherapeutic approaches for CLL should be aplied in early disease when immunosuppression is least encountered. We previously demonstrated the expression of a CT antigen, SEMG 1, in 3/9 patients with CLL. Furthermore, we also demonstrated that the presence of high titer IgG in the serum of patients expressing SEMG 1, suggesting the in vivo immunogenicity of SEMG 1 in the cancer-bearing autologous host. We have also recently used SEMG 1 as the bait in a yeast two-hybrid system of testicular cDNA library and identified that Protamine 1 is the interacting ligand of SEMG 1 and that Protamine 1 is also a novel CT antigen, suggesting that both SEMG 1 and Protamine 1 may be suitable antigens for tumor vaccine development. However, the expression of SEMG 1 and Protamine 1 in early CLL is unknown. We have in this study set out to determine whether or not SEMG 1 and/or Protamine 1 could be used for the design of tumor vaccine for the targeting of patients with early CLL, in particular, those with poor risk disease, as predicted by Zap 70 expression. Using pairs of sequence-specific primers in RT-PCR on a cohort of CLL (41 Stage 0/I and 6 Stage II/III), we found that SEMG 1 gene is expressed in 24/47 (51%) and Protamine 1 in 16/47 (34%) of CLL patients. Gene expression in most cases was associated with the detection by immunocytochemistry of SEMG 1 and/or Protamine 1 in the CLL cells. The expression frequency of SEMG1 and Protamine 1 in CLL did not appear to differ between early and late stage disease. 19/41 of patients with early stage disease and 5/6 of patients with late disease expressed SEMG 1; 12/41 of patients with early stage disease and 4/6 patients with late disease expressed Protamine 1. Furthermore, the expression of these antigens was equally distributed between Zap 70+ and Zap 70− CLL. SEMG 1 was expressed in 4/6 of Zap 70+ CLL (all 6 had early disease) and 2/9 of Zap 70− CLL (1/8 early disease and 1/1 late disease). Interestingly, although Protamine 1 expression in CLL predicted for SEMG 1 co-expression, only 67% of SEMG 1+ CLL expressed Protamine 1. Our results, therefore, suggest that both SEMG 1 and Protamine 1 are suitable targets for tumor vaccine development for some patients with early CLL, especially those with high risk disease, as predicted by Zap 70 expression.

Adherence to the BCLC guidelines and impact on overall survival.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 345-345 ◽  
Author(s):  
Jesna Mathew ◽  
Sasha Slipak ◽  
Anil Kotru ◽  
Joseph Blansfield ◽  
Nicole Woll ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Cox Regression ◽  
Early Stage ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Treatment Recommendations ◽  
Rank Test ◽  
P Value ◽  
Significant Difference

345 Background: Multiple studies exist that validate the prognostic value of the Barcelona Clinic Liver Cancer (BCLC) staging. However, none have established a survival benefit to the treatment recommendations. The aim of this study was to evaluate the adherence to the BCLC guidelines at a rural tertiary care center, and to determine the effect of following the treatment recommendations on overall survival. Methods: A retrospective chart review was conducted for 97 patients newly diagnosed with hepatocellular carcinoma (HCC) from 2000 to 2012. The treatment choice was compared with the BCLC guidelines and percentage adherence calculated. Overall survival was estimated using the Kaplan-Meier method and the log rank test was used to test the difference between the two groups. Cox regression tests were used to determine independent effects of stage, treatment aggressiveness, and guideline adherence on survival. A p-value <0.05 was considered statistically significant. Results: Of 97 patients, 75% (n=73) were male. Median overall survival was 12.9 months. In 59.8% (n=58) of the patients, treatment was adherent to stage specific guidelines proposed by the BCLC classification. There was no significant difference in overall survival between the adherent and non-adherent groups (11.2 vs 14.1 months, p<0.98). However on stage specific survival analysis, we noted a significant survival benefit for adherence to the guidelines for early stage HCC (27.9 vs 14.1 months, p<0.05), but a decrease in survival for adherence in the end stage (20 days vs 9.3 months, p<0.01). On univariate analysis, more aggressive treatment was associated with increased survival (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.22 to 0.87; p = 0.018). Multivariate analysis revealed that adherence did not independently affect survival when stage and aggressiveness of treatment were included in the model (HR, 1.3; 95% CI, 0.76 to 2.2, p = 0.34). Conclusions: Although the BCLC guidelines serve as a practical guide to the management of patients with HCC, they are not universally practiced. These results indicate that survival of patients with hepatocellular cancer is determined by stage and aggressiveness of treatment, not adherence to BCLC guidelines.

scholarly journals A Retrospective Analysis of Outcomes of Diffuse Large B Cell Lymphoma (DLBCL) in the Elder Patients in China

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5410-5410
Author(s):  
Peng Liu ◽  
Ying Han ◽  
Jianliang Yang ◽  
Xiaohui He ◽  
Changgong Zhang ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Early Stage ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
Early Stage Disease ◽  
Large B Cell Lymphoma ◽  
Elder Patients ◽  
Stage Disease ◽  
Ann Arbor ◽  
Advanced Disease Stage

Abstract Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis compared to the younger population, since older age is associated with comorbidity and suboptimal performance status leading to intolerance of chemo-immunotherapy. The outcome of DLBCL in the older patients (> 60 years) was well described in clinical trials with reported 5-year overall survival (OS) of 50-80% (Coiffier et al., N Engl J Med 2002). Since this group is often precluded from clinical trials and population-based studies are limited, optimal treatment strategy for the old patients with DLBCL remains controversial. Here, we describe a Chinese real-world experience of management of elderly DLBCL patients treated at National Cancer Hospital, China. Methods: This is a single-center, retrospective analysis of consecutive DLBCL patients aged ≥60 who planned to receive chemotherapy +/- rituximab. The standard regimens included 3-4 cycles (early stage disease) or 6 cycles (advanced) of R-CHOP like regimens (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by two rituximab doses in fit patients; R-miniCHOP for unfit and R-CE(etoposide)OP for frail elder patients. Patient data including baseline characteristics, histology, clinical parameters, and treatment outcomes were extracted from hospital medical records. The primary endpoint was progression-free survival (PFS); secondary endpoint was OS. Statistical analyses included descriptive statistics and Kaplan Meier estimates. Results: From June 2006 to December 2012, 349 patients aged ≥60 years were included, in which 204 patients were aged <70 years (Table 1). 326 patients received chemotherapy or chemo-immunotherapy with rituximab. Median follow up was 82 months. Five year PFS and OS of the elder patients were 45.8% and 51.9%, respectively. Significant difference was seen between patients < 70 years and those ≥70 years in terms of PFS (51.0% vs 38.6%, p=0.030) and OS (58.3% vs 42.8%, p=0.007) (Figure 1). Patients with early-stage disease (Ann Arbor StageⅠ/Ⅱ) had better 5-year PFS (60.1% vs 23.5%, p<0.001) and OS (65.3% vs 30.9%, p<0.001) than patients with advanced disease stage (Ann Arbor Stage III/IV) (Figure2). In addition, regimen including rituximab significantly improved the survival than chemotherapy alone (5-year PFS: 37.3% vs 64.0%, p<0.001; 5-year OS: 44.5% vs 69.3%, p<0.001), especially in patients ≥70 years, which almost doubled 5-year PFS and OS (5-year PFS: 25.4% vs 50.7%, p<0.001; 5-year OS: 28.8% vs 56.0%, p<0.001) (Figure3). Conclusions: Elder age (≥70 years) and advanced disease stage (Ann Arbor Stage III/IV) are associated with poor PFS and OS in Chinese elder DLBCL patients. The addition of rituximab significantly improves the survival compared to chemotherapy alone, especially in patients aged ≥70 years. These findings underscore the importance of personalized evaluation and treatment in elder patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Recent advances in understanding and managing cutaneous T-cell lymphomas

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 331
Author(s):  
Patrick M. Brunner ◽  
Constanze Jonak ◽  
Robert Knobler
Keyword(s):  
T Cell ◽  
Early Stage ◽  
Disease Stage ◽  
Treatment Modalities ◽  
Early Stage Disease ◽  
T Cell Lymphomas ◽  
Stage Disease ◽  
Related Quality ◽  
Health Related ◽  
Stage Ivb

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients’ health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.

Clinical and molecular characteristics of non-small cell lung cancer patients from rural Maine.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18237-e18237
Author(s):  
Antoine Harb ◽  
Adam Curtis ◽  
Laura Skacel ◽  
Michael Babcock ◽  
Marek Skacel
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
P53 Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Disease Free

e18237 Background: Non-Small Cell Lung Cancer (NSCLC) is the most common malignancy worldwide and the leading cause of malignancy-related mortality in the United States. The state of Maine in particular, has one of the highest rates of lung cancer in the country. Methods: We reviewed all NSCLC patients (adenocarcinoma (AC) and squamous cell (SC) histology) diagnosed between January 2017 and June 2018 at Northern Light Cancer Institute. 261 patients with clinical follow-up were identified. We correlated their clinical characteristics with molecular abnormalities identified by Next Generation Sequencing (NGS) and Fluorescence in situ hybridization, PD-L1 status by immunohistochemistry, disease-free and overall survival. Results: 210 patients had AC and 51 SC. They were evenly split between men and women. The median age at diagnosis was 68 years. 99% of patients were Caucasian. 15 patients were never smokers, the rest were equally divided between active and previous smokers. 44% had early stage disease (I/II) and 56% had late stage disease (III/IV) on presentation. 36.4% had a PD-L1 high status. The frequencies of the molecular aberrations identified in AC and SC are listed in the table below: Treatment differed by stage, including surgery/Radiation +/- adjuvant chemotherapy for early stage disease, definitive chemo-radiation followed by immunotherapy for stage III disease. Stage IV patients were treated with immunotherapy, combination chemo-immunotherapy, targeted therapy, palliative radiation and hospice referral. After a median follow-up of 10.6 months, overall survival (OS) was 66%. Disease free survival (DFS) was 33%. Using univariate (chi-square), multivariate (logistic regression) and Kaplan-Meier (log rank) analyses, we identified that in addition to a high clinical stage, which was associated with shorter OS and DFS, high PD-L1 status, and the presence of p53 mutation, were independent predictors of shorter OS, and p53 mutation of shorter DFS. Conclusions: NGS-based molecular testing deployed in real-time non-academic setting proved to be a valuable tool to identify therapeutic and prognostic targets in NSCLC. Besides those endorsed by the NCCN guidelines, p53 mutation is a common abnormality associated with adverse outcomes. While high PD-L1 expression is a desirable immunotherapy marker, its presence also predicted adverse overall outcomes in our patients.[Table: see text]

Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3056-3056
Author(s):  
B.E. Shaw ◽  
N.P. Mayor ◽  
A.-M. Little ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
...  
Keyword(s):  
Late Stage ◽  
Early Stage ◽  
Disease Stage ◽  
Unrelated Donor ◽  
Disease Relapse ◽  
Early Stage Disease ◽  
Hla Alleles ◽  
Graft Versus Host ◽  
Multiple Loci ◽  
Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6005-6015 ◽  
Author(s):  
Stephen J. Proctor ◽  
Jennifer Wilkinson ◽  
Gail Jones ◽  
Gillian C. Watson ◽  
Helen H. Lucraft ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cox Regression ◽  
Early Stage ◽  
Univariate Analysis ◽  
Central Element ◽  
Disease Stage ◽  
Advanced Stage ◽  
Early Stage Disease ◽  
Large Patient ◽  
Stage Disease

Abstract The SHIELD program for Hodgkin lymphoma in patients 60 years of age or older, prospectively evaluated clinical features and outcome in a large patient cohort (n = 175). The central element was a phase 2 study of VEPEMB chemotherapy (n = 103, median age 73 years) incorporating comorbidity assessment. A total of 72 other patients were treated off-study but registered prospectively and treated concurrently with: ABVD (n = 35); CLVPP (n = 19), or other (n = 18). Of VEPEMB patients, 31 had early-stage disease (stage 1A/2A) and received VEPEMB 3 times plus radiotherapy. Median follow-up was 36 months. Complete remission (CR) rate (intention-to-treat) was 74% and 3-year overall survival (OS) and progression-free survival (PFS) were 81% and 74%, respectively. A total of 72 patients had advanced-stage disease (stage 1B/2B/3 or 4) and received VEPEMB 6 times. CR rate was 61% with 3-year OS and PFS of 66% and 58%, respectively. Of patients achieving CR, 13% with early-stage and 5% with advanced-stage disease progressed. Overall treatment-related mortality was 7%. In patients treated with curative intent with VEPEMB, ABVD, and CLVPP (n = 157), CR linked to several factors in univariate analysis. In a Cox regression model only, obtaining CR remained significant for OS and CR plus comorbidity and age for PFS. RS-EBV status had no significant effect on outcome.

scholarly journals Molecular estimation of neurodegeneration pseudotime in older brains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumit Mukherjee ◽  
Laura Heath ◽  
Christoph Preuss ◽  
Suman Jayadev ◽  
Gwenn A. Garden ◽  
...  
Keyword(s):  
Late Stage ◽  
Late Onset ◽  
Early Stage ◽  
Disease Onset ◽  
Postmortem Brain ◽  
Disease Stage ◽  
Rna Seq ◽  
Early Stage Disease ◽  
Molecular Changes ◽  
Stage Disease

AbstractThe temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.

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