scholarly journals Expression of ASPN with Prognostic Values in Gastric Cancer: A Study Based on TCGA Data

Author(s):  
wen chao li ◽  
Zhe Xu ◽  
Hui Chen ◽  
Zhen dong Wang ◽  
Yang Xu ◽  
...  

Abstract Objective: Gastric ancer is a common cancer with high cancer-related death in the world Although, ASPN has been reported as a potential biomarker in some cancers, the relationship of ASPN and clinical pathologic features in gastric cancer has not been investigated thoroughly. Thus, the aim of study is to evaluate the function of ASPN in gastric cancer based on TCGA. Materials and methods: The gene expression data (407 cases, Workflow Type: HTSeq-Counts) and corresponding clinical information were downloaded from the TCGA Genomic Data Commons data portal. We performed the NES and nominal p value to evaluate the pathways enriched in each phenotype. Then, we analyzed the association with ASPN and clinicopathologic variables based on Wilcoxon signed-rank test and logistic regression. Result: We found that it was significantly different in ASPN expression between gastric cancer and normal tissue (P<0.001). High ASPN expression was significantly associated with high stage (Odds ratio (OR)=3.656 for stage II vs stage I and OR=0.014 for stage III vs stage I), T classification (OR=13.304 for T2 vs T1, OR=20.769 for T3 vs T1 and OR=24.857 for T4 vs T1) (all p-values< 0.05). Univariate analysis revealed ASPN could result in poor overall survival with HR=1.004 and P=0.036. Besides, multivariate analysis indicated that ASPN expression was an independent risk factor for overall survival (HR:1.010, P=0.000), age (HR: 1.046, P=0.002) and gender (HR: 1.623, P=0.026). Besides, GSEA results showed that Pentose phosphate pathway, Base excision repair, Peroxisome, Protesome, Nucleotide excision repair, and Mismatch repair were differentially enriched in gastric cancer with high ASPN expression phentype. Conclusion: ASPN expression is higher in gastric cancer than normal tissues, and considered ASPN as a potential independent molecular marker for diagnosis and prognosis of GC.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 345-345 ◽  
Author(s):  
Jesna Mathew ◽  
Sasha Slipak ◽  
Anil Kotru ◽  
Joseph Blansfield ◽  
Nicole Woll ◽  
...  

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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17542-17542
Author(s):  
A. Lal ◽  
S. Adil ◽  
N. Masood

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 327-327
Author(s):  
Mónica Isabel Meneses Medina ◽  
Ana Karen Valenzuela ◽  
Jorge Humberto Hernandez-Felix ◽  
Haydee Cristina Verduzco-Aguirre ◽  
Vanessa Rosas Camargo ◽  
...  

327 Background: Advanced gastric cancer (GC) is a disease with high morbidity and poor prognosis. We hypothesize that different sites of metastasis have different impact in terms of symptoms and complications. We sought to evaluate if site specific morbidity in our patients impacted treatment and survival. Methods: Medical records from patients with advanced GC treated from Jan 2005 to Dec 2015 were retrospectively reviewed. Morbidity was defined as having any symptom by metastases in a specific site. OS was estimated by Kaplan Meier method and compared by Log-rank test. P value < 0.05 was considered significant. Results: We included 180 consecutive patients, median age at diagnosis was 56 years (21-90), 55% were women. Most common sites of metastases were: peritoneum 76.1%, non-regional lymph nodes 38.9%, liver 22.8%, lung 26.7%, bone 9.4% and ovary 12.8%. Regarding morbidity, at diagnosis 68% of patients presented morbidity by the primary tumor: obstruction 56%, bleeding 27%, obstruction and bleeding 3%, other 14%. Disease by peritoneum caused morbidity in 30%, by lung in 8%, by ovarian in 4.4%, by lymph nodes in 3.3%, and by other sites in 5.6% of patients. OS in the global cohort was: 3.53 months (2.2 to 4.8), nevertheless by univariate analysis we found that OS was affected by morbidity at some sites as it is show in table. More patients with peritoneal morbidity could not receive treatment vs those without peritoneal morbidity (p = 0.042). Conclusions: We found that morbidity in peritoneum, lung and ovary adversely affected prognosis of patients with advanced GC. Moreover, peritoneal morbidity preclude patients from receiving oncological treatment. [Table: see text]


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 169-169
Author(s):  
Takeru Wakatsuki ◽  
Keisho Chin ◽  
Satoshi Matsusaka ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  

169 Background: ToGA study showed significant survival benefit of trastuzumab in patients with HER2 positive gastric cancer (GC); however, clinical factors which can impact its efficacy prior to treatment are still unknown. Hence, we conducted this exploratory analysis whether clinical factors could influence trastuzumab efficacy in patients with HER2 positive GC. Methods: Thirty-three HER2 positive GC patients, who were treated by trastuzumab with chemotherapy in our institute from 2011 March to 2012 December, were enrolled. Clinical factors according to ToGA study and tumor markers were examined. We retrospectively analyzed whether these clinical factors were associated with progression-free survival (PFS) and overall survival (OS). These endpoints were estimated using by Kaplan-Meier methods and compared by the log-rank test. The Cox regression analysis including only clinical factors of which p-value was less than 0.02 was done. Results: Median follow-up period was 10.8 months. Median age was 63 y.o. and 64% of the patients were male. PS 0-1, GEJ cancer, visceral metastasis (lung or liver), previous gastorectomy, previous chemotherapy, number of metastatic site (1-2), and number of metastatic lesion (1-4) were found in 97%, 27%, 58%, 36%, 21%, 76%, and 27% of the patients, respectively. Sixty-seven% and 94% of the patients were differentiated type and HER2 3+ by IHC, respectively. Baseline median CEA and CA19-9 levels were 5.2 ng/ml and 109.4 U/ml, respectively. Median PFS was 9.5 months (95% CI: 5.5-13.5) and median OS was not reached. Overall response rate by RECIST was 71.4%. Lower CA19-9 levels were associated with longer PFS in univariate analysis. Patients who had lower CA 19-9 levels showed a median PFS of 12.2 months vs. 6.9 months for patients who had higher CA19-9 levels (HR: 0.41 [95%CI: 0.17-1.00], p=0.042), however this result was not conserved in multivariate analysis. No clinical factors were associated with OS. Conclusions: Lower CA19-9 levels were associated with favorable PFS in the patients with HER2 positive GC upon when treated by trastuzunab. External clinical validations and further molecular analyses are needed to validate this result.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 155-155
Author(s):  
A. O. Kaseb ◽  
J. Morris ◽  
M. Hassan ◽  
E. Lin ◽  
L. Xiao ◽  
...  

155 Background: Hepatocellular carcinoma (HCC) is a vascular tumor, derived mainly by vascular endothelial growth factor (VEGF)-mediated angiogenesis. It is always associated with chronic liver disease (CLD) and cirrhosis, which directly affect survival of HCC patients. Insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, and therefore, CLD is associated with low levels of IGF-1. Methods: 288 new consecutive patients with HCC were eligible for the study between 2001 and 2008 at M. D. Anderson Cancer Center. Baseline clinicopathologic features, CLIP and BCLC staging, plasma IGF-1 and VEGF levels were available and multivariate Cox regression models and median survival were calculated. Kaplan-Meier curves were used to estimate overall survival and the log-rank test was used to compare survival probabilities in patients with different IGF-1 and VEGF levels. Recursive partitioning was used to determine the optimal cut point for IGF-1 and VEGF, using repeated training/validation samples, each using 2/3 of the data to determine the best cut point and the remaining 1/3 to validate it. Prognostic ability of different molecular staging systems was compared using C-index. Results: Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor overall survival, with an optimal cut point of 26 pg/mL and 450 pg/mL respectively. The combination of low IGF-1 and high VEGF predicts median OS of 2.7 months compared with 19 month for patients with high IGF-1 and low VEGF (p-value=<0.0001), and further refines the prognostic ability of BCLC and CLIP HCC staging systems (p<0.0001). Conclusions: Molecular classification of HCC using baseline plasma IGF-1 and VEGF significantly correlated with clinical features and survival of HCC patients. Furthermore, integrating IGF-1 and VEGF into HCC staging systems, CLIP and BCLC, significantly enhanced their ability to predict prognosis. It may prove to be useful in designing strategies to personalize treatment approaches to these patients. No significant financial relationships to disclose.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1086
Author(s):  
Shun Ohmori ◽  
Yu Sawada ◽  
Natsuko Saito-Sasaki ◽  
Sayaka Sato ◽  
Yoko Minokawa ◽  
...  

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.


2020 ◽  
Vol 28 (1) ◽  
pp. 138-151
Author(s):  
Kelly A. Stahl ◽  
Elizabeth J. Olecki ◽  
Matthew E. Dixon ◽  
June S. Peng ◽  
Madeline B. Torres ◽  
...  

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuyun Wu ◽  
Ningbo Hao ◽  
Suming Wang ◽  
Xin Yang ◽  
Yufeng Xiao ◽  
...  

Gastric cancer (GC) is one of the most common malignancies worldwide, and the tumor metastasis leads to poor outcomes of GC patients. Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules that play a crucial role in tumor metastasis. However, the biological function and underlying mechanism of numerous lncRNAs in GC metastasis remain largely unclear. Here, we report a novel lncRNA, lnc-TLN2-4:1, whose expression is decreased in GC tissue versus matched normal tissue, and its low expression is involved in the lymph node and distant metastases of GC, as well as poor overall survival rates of GC patients. We further found that lnc-TLN2-4:1 inhibits the ability of GC cells to migrate and invade but does not influence GC cell proliferation and confirmed that lnc-TLN2-4:1 is mainly located in the cytoplasm of GC cells. We then found that lnc-TLN2-4:1 increases the mRNA and protein expression of TLN2 in GC cells and there is a positive correlation between the expression of lnc-TLN2-4:1 and TLN2 mRNA in GC tissue. Collectively, we identified a novel lncRNA, lnc-TLN2-4:1, in GC, where lnc-TLN2-4:1 represses cell migration and invasion. The low expression of lnc-TLN2-4:1 is associated with poor overall survival rates of GC patients. These suggest that lnc-TLN2-4:1 may be a tumor suppressor during GC metastasis.


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