scholarly journals High expression of CD34 protein in stage IIA rectal cancer is independently associated with better prognosis

2021 ◽  
Vol 108 (Supplement_4) ◽  
Author(s):  
A Lalos ◽  
A Wilhelm ◽  
S Staubli ◽  
A Posabella ◽  
B Weixler ◽  
...  

Abstract Objective Colorectal cancer (CRC) remains the third most common cause of death from malignancies, while 30% of all these tumors develop in the rectum. The proximity of the rectum to vital structures, and in some cases the use of neoadjuvant treatment, make the surgical resection of this tumor a great challenge even for highly qualified surgeons. Understanding the mechanisms of rectal cancer (RC) development could lead to new concepts in the approach of diagnosis, prognosis, and eventually treatment of this disease. Despite the fact that TNM classification represents the gold standard tool for the staging of RC, a significant number of studies has recently focused on the association between the tumor microenvironment and RC. CD34 is a transmembrane phosphoglycoprotein expressed on human hematopoietic progenitor and vascular endothelial cells, as well in malignant tissues. It has also been shown to be involved in tumor invasion and angiogenesis. Because of the controversial data , we examined the expression of CD34 protein in RC specimens after stratifying the patients according to their UICC stage. Methods In our retrospective study, we included 364 patients with unselected, clinically annotated primary RC specimens. We analyzed a tissue microarray (TMA) of these specimens by immunohistochemistry (IHC) for the expression of CD34 protein by tumor cells. Results After stratifying the patients in nodal negative and positive groups, we found that the patients with Stage IIA tumors and high expression of CD34 protein had a favorable 5-year overall survival rate (53%; 95%CI = 40.0 – 65.1%) compared to tumors without expression of CD34 protein (26%; 95%CI = 10.7 – 44.6%, p = 0.003). Univariate and multivariate Hazard Cox regression survival analysis revealed that the combined the expression of CD34 protein was an independent, favorable, prognostic marker for overall survival in the stage IIA RC (HR = 0.39, 95%CI = 0.19 – 0.79; p = 0.009). Conclusion Our data show that the expression of CD34 protein represents an independent, favorable, prognostic condition in nodal negative stage IIA RC. Thereby, we provide novel insights into the prognostic role of the tumor microenvironment in RC that might help in the development of novel treatment modalities by its modification.

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaojie Chen ◽  
Feifei Huang ◽  
Shangxiang Chen ◽  
Yinting Chen ◽  
Jiajia Li ◽  
...  

ObjectiveGrowing evidence has highlighted that the immune and stromal cells that infiltrate in pancreatic cancer microenvironment significantly influence tumor progression. However, reliable microenvironment-related prognostic gene signatures are yet to be established. The present study aimed to elucidate tumor microenvironment-related prognostic genes in pancreatic cancer.MethodsWe applied the ESTIMATE algorithm to categorize patients with pancreatic cancer from TCGA dataset into high and low immune/stromal score groups and determined their differentially expressed genes. Then, univariate and LASSO Cox regression was performed to identify overall survival-related differentially expressed genes (DEGs). And multivariate Cox regression analysis was used to screen independent prognostic genes and construct a risk score model. Finally, the performance of the risk score model was evaluated by Kaplan-Meier curve, time-dependent receiver operating characteristic and Harrell’s concordance index.ResultsThe overall survival analysis demonstrated that high immune/stromal score groups were closely associated with poor prognosis. The multivariate Cox regression analysis indicated that the signatures of four genes, including TRPC7, CXCL10, CUX2, and COL2A1, were independent prognostic factors. Subsequently, the risk prediction model constructed by those genes was superior to AJCC staging as evaluated by time-dependent receiver operating characteristic and Harrell’s concordance index, and both KRAS and TP53 mutations were closely associated with high risk scores. In addition, CXCL10 was predominantly expressed by tumor associated macrophages and its receptor CXCR3 was highly expressed in T cells at the single-cell level.ConclusionsThis study comprehensively investigated the tumor microenvironment and verified immune/stromal-related biomarkers for pancreatic cancer.


Author(s):  
Patrick Sven Plum ◽  
Heike Löser ◽  
Thomas Zander ◽  
Ahlem Essakly ◽  
Christiane J. Bruns ◽  
...  

Abstract Purpose Driver mutations are typically absent in esophageal adenocarcinoma (EAC). Mostly, oncogenes are amplified as driving molecular events (including GATA6-amplification in 14% of cases). However, only little is known about its biological function and clinical relevance. Methods We examined a large number of EAC (n = 496) for their GATA6 amplification by fluorescence in situ hybridization (FISH) analyzing both primary resected (n = 219) and neoadjuvant treated EAC (n = 277). Results were correlated to clinicopathological data and known mutations/amplifications in our EAC-cohort. Results GATA6 amplification was detectable in 49 (9.9%) EACs of our cohort. We observed an enrichment of GATA6-positive tumors among patients after neoadjuvant treatment (12,3% amplified tumors versus 6,8% in the primary resected group; p = 0.044). Additionally, there was a simultaneous amplification of PIK3CA and GATA6 (p < 0.001) not detectable when analyzing other genes such as EGFR, ERBB2, KRAS or MDM2. Although we did not identify a survival difference depending on GATA6 in the entire cohort (p = 0.212), GATA6 amplification was associated with prolonged overall survival among patients with primary surgery (median overall-survival 121.1 vs. 41.4 months, p = 0.032). Multivariate cox-regression analysis did not confirm GATA6 as an independent prognostic marker, neither in the entire cohort (p = 0.210), nor in the subgroup with (p = 0.655) or without pretreatment (p = 0.961). Conclusions Our study investigates the relevance of GATA6 amplification on a large tumor collective, which includes primary resected tumors and the clinically relevant group of neoadjuvant treated EACs. Especially in the pretreated group, we found an accumulation of GATA6-amplified tumors (12.3%) and a frequent co-amplification of PIK3CA. Our data suggest an increased resistance to radio-chemotherapy in GATA6-amplified tumors.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13585-13585
Author(s):  
J. C. Marin Marmolejo ◽  
C. R. Villegas Mejia ◽  
J. P. Cardona Arcila ◽  
E. Mulett Vasquez ◽  
M. Osorio Chica ◽  
...  

13585 Background: According to the TNM classification, the prognosis of patients suffering from colon and rectal cancer has been defined taking into account the number of nodes reported positively. Objective: This work is intending to establish a relation between the number of positive nodes and the number of dissected nodes, relating it with the overall survival. Methods: 5500 medical records of patients were reviewed. 771 out of these corresponded to gastrointestinal cancer (14%) from which 351(6.38%) corresponded to colorectal cancer. From this group, 291 patients (82.9%) underwent a surgery. A relation between the number of positive nodes and the number of dissected nodes was established and called proportion of positivity (positive nodes/ dissected nodes × 100) and this was in turn related to a five year overall survival. Two groups were analyzed: proportion of positivity > than 50% and proportion of positivity < than 50%. Results: A report of 209 patients showing nodes was obtained (59.5%), with a means of 10.4 (rank 0–31) of dissected nodes per patient and a means of positive nodes of 2.4 (rank 0–22). Comparing the two groups the statistic significance starts to be obvious from the 18 months and the difference between the two groups continues increasing until the five years. The survival to five years for the group with the proportion > than 50% was 39% (IC 95%:13.4–64.5) compared to the survival for the group with a proportion < than 50% that was 75.7% (IC 95%:67.6–83.7) p<0.05. Conclusions: The proposal shows that not only is the absolute number of positive dissected nodes as only prognostic indicator (TNM) but also that before nodes dissections with low number of them, it is possible to establish a reliable prognostic relationship by calculating the proportion of positivity. The above said does not consider that the nodal dissection can be less than recommended, on the contrary obtaining the biggest number of nodes will mean bigger equivalence of the proposal and a bigger possibility to detect positive nodes. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15549-e15549
Author(s):  
J. W. Horvath ◽  
W. Frankel ◽  
A. Bellizzi ◽  
K. Guenterberg ◽  
O. H. Iwenofu

e15549 Background: The biologic behavior of gastrointestinal stromal tumors (GIST) based upon morphologic parameters is unpredictable. Cyclin dependent kinase-1 (Cks1) plays an important role in the ubiquitination and proteolysis of p27kip1, a negative regulator of protein kinase Cdk2/cyclin E and Cdk2/cyclin A. This study was to ascertain whether Cks1 overexpression and p27kip1 downregulation were predictive of biologic aggressiveness and overall survival in GIST. Methods: Tissue microarray was built from 61 patients with GIST. Pathology reports as well as clinical follow-up were retrieved. Sections were stained with antibodies to p27kip1 and Cks1. Staining was scored for quantity of tumor cells (%) and intensity (0, 1+ weak staining, 2+ strong staining), and a score was calculated from the product of intensity and %. Tumors were evaluated for correlation of p27kip1 and Cks1 expression level with overall survival time and tumor risk stratification. Tumor risk stratification was classified into very low risk, low risk, intermediate risk, and high risk, and is reflective of intrinsic biologic aggressiveness. Actuarial survival curves were estimated using Kaplan Meier method. Results: The tumors show a high frequency of Cks1 expression (92%; 1+, n=39; 2+, n=17). The % expression ranged from 0–90% (mean 37%). The p27kip1 positive rate is 85% (1+, n=20; 2+, n=32). The % expression ranged from 0–90% (mean 48%). Overall survival ranged from 0.1–10.7 years. By univariate analysis of overall survival using Cox regression model, increased p27kip1 expression (continuous variable) is significantly correlated with overall survival (p=0.04), but Cks1 expression does not (p=0.84). In a univariate analysis of p27kip1 and Cks1 (continuous variables) with risk stratification of the tumor using F-test, higher tumor grade has significantly higher Cks1 expression values (p=0.0045). Conclusions: Our study shows that with univariate analysis high expression of Cks1 expression is significantly associated with increased intrinsic biologic aggressiveness, while high expression of p27kip1 is associated with increased overall survival. The lack of correlation of Cks1 and p27kip1 suggests additional p27kip1 independent mechanisms might play a role in the oncogenesis of GIST. No significant financial relationships to disclose.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 314-314
Author(s):  
Tobin Joel Crill Strom ◽  
Sarah E. Hoffe ◽  
Shivakumar Vignesh ◽  
Jason Klapman ◽  
Cynthia L. Harris ◽  
...  

314 Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 >90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.


2020 ◽  
Author(s):  
Junhao Yin ◽  
Xiaoli Zeng ◽  
Zexin Ai ◽  
Miao Yu ◽  
Yang'ou Wu ◽  
...  

Abstract Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease that emerged as a major international health concern, associated with poor prognosis and the absence of specific biomarkers. Studies have shown that the ferroptosis-related genes (FRGs) can be used as tumor prognostic markers. However, FRGs’ prognostic value in OSCC needs further exploration. Our aim was to construct a novel FRG signature for overall survival (OS) prediction in OSCC patients and explore its role in immunotherapy.Methods: In our study, gene expression profile and clinical data of OSCC patients were collected from a public domain. FRGs were available from the FerrDb database. We performed univariate and multivariate Cox regression analyses to construct a multigene signature. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) methods were utilized to test the effectiveness of the FRG signature. A differential gene expression analysis was performed by the limma R package, followed by functional enrichment analyses. CIBERSORT was applied to analyze the tumor microenvironment (TME). Finally, the expression of human leukocyte antigen (HLA) and immune checkpoint molecules were analyzed to confirm the sensitivity of immunotherapy.Results: A total of 103 FRGs, expressed in OSCC (FRGs-OSCC), were identified from the two datasets by the Venn analysis. The Cox regression analysis identified 5 FRGs-OSCC that were associated with overall survival (all P < 0.01). The FRGs-OSCC risk model was established to classify patients into high risk and low risk groups. Compared with the low risk group, the survival time of the high-risk group was significantly reduced (P < 0.001). According to the multivariate Cox regression analyses, the risk score acted as an independent predictor for OS (HR > 1, P < 0.001). The accuracy of the FRGs-OSCC risk predictive model was confirmed by ROC curve analysis. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed significant enrichment of immune-related pathways, and a difference in tumor microenvironment between the two groups. The low risk group had the characteristics of higher expression of HLA and immune checkpoints (IDO1, LAG3, PDCD1 and TIGHT), a lower tumor purity and a higher infiltration of immune cells, indicating a more sensitive response to immunotherapy.Conclusions: The novel FRGs-OSCC risk score system can be used to predict OSCC prognosis. Ferroptosis targeting may be a therapeutic option for OSCC.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi114-vi114
Author(s):  
Josiah An ◽  
Adithya Chennamadhavuni ◽  
Sarah Mott ◽  
Rohan Garje

Abstract BACKGROUND Glioblastoma is one of the most aggressive and commonly encountered brain tumors. Standard of care includes surgical resection with adjuvant or concurrent chemoradiation which is predominantly based on adult clinical trials. Our study objective was to assess whether survival differed in AYA compared to older adults. METHODS The National Cancer Database was used to identify patients with at least surgically resected glioblastoma from 2004 to 2016. Cox regression models were utilized to estimate the effect of treatment on overall survival (OS) while accounting for immortal time bias (3-months) and clustering within facility. RESULTS Among 51,718 patients with glioblastoma identified, 2,930 patients were AYA. Multivariable analysis (MVA) shows OS was significantly higher in AYA, female, non-white, high income, unilateral cancer patients with private insurance receiving treatments in high volume facilities. OS among AYA patients was significantly lower in surgery + (radiation or chemotherapy: S+(RT or CT) group compared to surgery only (S) (HR=1.33, 95% CI 1.06–1.65), but no significant survival difference between surgery + chemoradiation (S+C+RT) groups and surgery only (HR=0.97, 95% CI 0.83–1.14). Median survival is ~28 months in AYA among S and S+C+RT groups whereas significantly lower survival (median OS ~18 months) is seen in S+RT or CT. Non-AYA patients were at 2 times increased risk of death compared to AYA patients who received the same type of treatment. CONCLUSIONS In conclusion, AYA population has more than twice the median OS in comparison to non-AYA patients. Worse overall survival was seen among S+RT or CT in comparison to S and S+RT+CT in AYA group. For patients needing either chemotherapy or radiation with surgery, possibly a trimodal approach might provide better survival advantage. Prospective studies are needed to further explore optimal treatment modalities in this unique population.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15162-e15162
Author(s):  
Yanhong Deng ◽  
Yue Cai ◽  
Jianwei Zhang ◽  
Huabin Hu ◽  
Jiayu Ling ◽  
...  

e15162 Background: NAR score is considered as a surrogate endpoint for survival in patients with locally advanced rectal cancer who received neoadjuvant treatment. Here we validate it in Chinese FOWARC study, especially in the chemotherapy alone arm. Methods: NAR score is calculated based on cT, ypT, ypN as reported for patients who received surgery in FOWARC study. NAR score is correlated to DFS with COX regression and Kaplan-Meier analysis. Results: 451 patients had surgery, 147 in FU-RT group, 152 in FOLFOX-RT arm and 152 in FOLFOX arm. NAR score is a significant prognostic factor in COX regression (P=0.000, HR 1.034, 95% CI 1.024-1.045) and in FOLFOX alone group (p=0.001, HR 1.030, 95% CI 1.013-1.047). When NAR score is quartile to <5, 5-10, 10-15,>15, the survival of patients is listed below, and similar to pathological staging. Conclusions: NAR score can be used as a surrogate endpoint for disease free survival Chinese patients. But it is not superior to pathological stage, especially in patients who received chemotherapy alone. [Table: see text]


2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
SA Rahman ◽  
RC Walker ◽  
T Crosby ◽  
N Maynard ◽  
DA Cromwell ◽  
...  

Abstract Introduction For patients with oesophageal cancer, producing accurate prediction models for survival after oesophagectomy has proved challenging. We investigated whether Random Survival Forests (RSF), a novel machine learning method, could produce an accurate prognostic model for overall survival after oesophagectomy. Method The study used data from the National Oesophago-Gastric Cancer Audit and included patients diagnosed with oesophageal adenocarcinoma or squamous cell carcinoma between 2012 and 2018 in England and Wales and who underwent a curative oesophagectomy with adequate lymphadenectomy (15 LN) and survived to discharge (n=6198). Missing data was handled using multiple imputation and the data was split into training and validation cohorts. 13 variables were selected for inclusion using Random Forest variable importance and used to train the final model. The same variables were used to develop a traditional Cox regression model. Result Median survival was 53 months in both cohorts. The final RSF model had good discrimination in the validation cohort with a C-index of 0.757(0.755-0.759), exceeding the Cox model; 0.748(0.746-0.750). At 3 years post-surgery, overall survival was 56.2%. The RSF yielded a mean predicted survival of 55.8%(IQR 29.5%-81.7%) compared to 55.4%(40.0%-77.7%) for the Cox model. The most important variables were lymph node involvement and pT/ypT stage, however other variables including neoadjuvant treatment completion and surgical complications were also found to be important. Conculsion A Random Forest survival model provided better performance in predicting survival after curative oesophagectomy. This will allow more personalised predictions to be delivered clinicians and patients. Take-home message Random Forest survival models can accurately predict post-operative prognosis after oesophagectomy.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Fang Liu ◽  
Yuan He ◽  
Qinghua Cao ◽  
Ni Liu ◽  
Wenhui Zhang

Objective. To investigate the expression of transducin- (β-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance.Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC.Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (P<0.05). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis (P=0.000) and advanced TNM stage (P=0.001). Moreover, high levels of TBL1XR1 predicted worse overall survival (P=0.015). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367–0.752;P=0.005).Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients.


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