scholarly journals Prognostic significance of CD163+ tumor-associated macrophages in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tao Xue ◽  
Kejing Yan ◽  
Yiqi Cai ◽  
Jiancheng Sun ◽  
Zhejing Chen ◽  
...  

Abstract Background This study aimed to explore the prognostic significance of tumor-associated macrophage (TAM) infiltration in colorectal cancer (CRC) patients. Methods Tissue microarray and immunohistochemistry were used to detect the infiltration of CD163+ TAMs in 209 CRC samples, and the Kaplan–Meier method was used for survival analysis. Cox proportional hazards analysis was used for univariate analysis and multivariate analysis of clinically relevant confounders. Results The samples were divided into low-level (n = 105) and high-level infiltration groups (n = 104) by the median number of CD163+ TAMs detected. The overall survival (OS) and disease-free survival (DFS) of CRC patients in the low-level CD163+ TAM infiltration group were longer than those in the high-level CD163+ TAM infiltration group (P < 0.001). Infiltration of CD163+ TAMs in CRC tissues was a negative prognostic factor for CRC patients. Risks of death and disease recurrence for CRC patients in the low-level CD163+ TAM infiltration group were lower than those in the high-level CD163+ TAM infiltration group (HROS = 0.183, 95% CI 0.052–0.647, P = 0.008; HRDFS = 0.191, 95% CI 0.078–0.470, P = 0.000). Conclusions The infiltration of CD163+ TAMs in CRC tissue is an independent adverse factor for the prognosis of CRC patients. High-level infiltration of CD163+ TAMs is associated with shorter OS and DFS.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Aline Fusco Fares ◽  
Daniel Vilarim Araujo ◽  
Eliza Dalsasso Ricardo ◽  
Marcelo Corassa ◽  
Maria Nirvana Cruz Formiga ◽  
...  

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4529-4529
Author(s):  
Bernadett Szabados ◽  
Marlon Rebelatto ◽  
Craig Barker ◽  
Alvin Milner ◽  
Arthur Lewis ◽  
...  

4529 Background: The biomarkers PD-L1, FOXP3, and CD8 have been explored in pts with advanced UC who progressed after platinum-based chemotherapy (CTx). However, their relevance earlier in the disease process is less well understood. Methods: The Phase 2/3 LaMB study (NCT00949455) compared maintenance lapatinib vs placebo after first-line (1L) platinum-based CTx in pts with HER1/HER2-overexpressing stage IV advanced UC. Pre-CTx archival samples from this study were retrospectively analyzed and included both randomized and screen failure pts. PD-L1 expression was assessed (VENTANA SP263 Assay) and categorized as high (≥25% of tumor cells [TC] and/or immune cells [IC]) or low/negative ( < 25% TC and IC). Overall survival (OS) and progression-free survival (PFS) were estimated via Kaplan-Meier method; results were stratified by PD-L1 expression. The exploratory biomarkers CD8 and FOXP3 were also analyzed. The prognostic significance of the biomarkers was explored by multivariable Cox proportional hazards models and a bootstrap method for model selection. Results: Of 446 pts (232 randomized; 214 screened), 243 (54.5%) were assessed for PD-L1 expression, with 61 (25.1%) PD-L1 high and 158 (65.0%) PD-L1 low/negative. In PD-L1 high and low/negative pts, respectively, median OS (95% CI) was 12.0 (9.4–19.7) vs 12.5 months (10.4–15.5); median PFS (95% CI) was 6.5 (3.5–8.8) vs 5.0 months (4.3–6.3). PD-L1 expression was not associated with OS or PFS in univariate analysis or in a multivariate model for OS (hazard ratio [HR] for PD-L1 high vs low/negative 1.4 [95% CI, 0.8–2.3]). In a multivariate model for PFS, PD-L1 expression improved accuracy of the model by 23% and was a significant variable (HR, 2.1 [95% CI, 1.2–3.5]). Results of analyses of CD8 and FOXP3 will also be reported. Conclusions: Overall, these data suggest a lack of association between PD-L1 expression and survival in pts receiving 1L platinum-based CTx. Mechanisms underlying the potential association of PD-L1 expression with PFS remain unclear. CD8 and FoxP3 exploratory analyses may help to elucidate these results. Clinical trial information: NCT00949455.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8510-8510
Author(s):  
A. M. Evens ◽  
K. A. David ◽  
I. Helenowski ◽  
S. M. Kircher ◽  
L. Mauro ◽  
...  

8510 Background: PTLD has a reported 3-year (yr) overall survival (OS) of 35–40% (Leblond, JCO 2001). The impact of rituximab (RTX) on the prognosis or outcome of PTLD is not known. Methods: We examined the clinical features, treatment, and outcomes among a large population-based cohort of SOT-related PTLD patients (pts) at 4 Chicago institutions (1/98–2/08). Prognostic factors were evaluated in univariate and Cox proportional hazards regression for survival. Results: 81 PTLD pts were identified (SOT: 47 kidney ± pancreas, 4 pancreas, 17 liver, 8 heart, 5 lung) with median age at diagnosis (dx) of 48 yrs (range 20–72). Median time from SOT to PTLD was 42 months (mo) (range 1–216 mo). PTLD dx (per WHO) were 55 monomorphic, 22 polymorphic and 4 plasmacytic, while 42 were EBV+ and 30 EBV-negative (9 unknown). 74% of pts (60/81) were treated with rituximab ± chemotherapy (and reduction of immune suppression). With 38-mo median followup for all pts, 3-yr progression-free (PFS) was 58% and 3-yr OS 62%, despite 16% of pts dying ≤ 6 weeks from dx. Most relapses (30/32) occurred ≤ 12 months from dx. Pts receiving RTX as part of therapy had 3-yr PFS of 69% and OS 71% (vs 21% (p=0.0002) and 33% (p=0.001), respectively, without RTX). Univariate analysis identified prognostic factors for PFS/OS (all <0.01): 1) PS, 2) serum albumin, 3) >1 EN site, 4) marrow involvement, 5) CNS disease and 6) RTX as part of initial therapy. Neither histology nor EBV status predicted outcome. On multivariate analysis, 4 factors remained significant ( Table 1a ). Further, a survival model based on 3 factors was constructed ( Table 1b ). Conclusions: This study represents the largest PTLD report in RTX-treated pts. We are the first to identify the prognostic significance of low albumin and a low PTLD relapse rate beyond 1 yr (6.3%). Further, it appears that the introduction of RTX has improved the survival of PTLD. In addition, clinical factors at dx identified pts with markedly divergent outcomes. [Table: see text] [Table: see text] No significant financial relationships to disclose.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 563-563
Author(s):  
Julia Alcaide ◽  
Antonio Rueda ◽  
Isabel Rodrigo ◽  
Teresa Tellez ◽  
Rafael Funez ◽  
...  

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p<0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p<0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p<0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21530-e21530
Author(s):  
Ki Hyang Kim ◽  
Jae Jin Lee ◽  
Jongphil Kim ◽  
Fabio Renato Morgado Gomes ◽  
Marina Sehovic ◽  
...  

e21530 Background: In geriatric assessments, comorbidity is often assessed with tools such as the Charlson comorbidity index (CCI) and the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). In studies of older patients with colorectal cancer (CRC), comorbidity was mainly measured using the CCI, and inconsistent results about the correlation comorbidity with overall survival (OS) were found. In order to refine our understanding of the impact of comorbidity, we evaluated its correlation with OS using the CIRS-G and heat maps to elicit the subgroups with the highest impact. Methods: We retrospectively reviewed 153 consecutive patients from the Total Cancer Care database, aged ≥65 with stage 4 CRC, who underwent chemotherapy at Moffitt Cancer Center from 2000 to 2015. The association between CIRS-G scores and OS was examined by the Cox proportional hazards regression model. Results: Median age at diagnosis was 71 years. Forty-eight % of patients had an ECOG PS of 0. Median MAX2 score of chemotherapies was 0.119. Median total score of CIRS-G was 8 (1-20) and median severity index was 0.57 (0.07-1.43). The most common comorbidities were vascular, EENT and larynx, and respiratory diseases. Eleven patients had 1 comorbidity and 1 patient had 2 comorbidities at level 4 severity. Median OS of all patients was 25.1 months (95% CI 21.2-27.6). In univariate analysis, the number of CIRS-G level 4 comorbidities was a significant worse prognostic factor for OS (0 vs 1 or 2, HR 2.16, p = 0.017). In multivariate analysis, ECOG PS ≥2, poorly differentiated histology, age at diagnosis and numbers of CIRS-G level 4 comorbidities were significant worse prognostic factors for OS. ECOG PS ≥2 and age at diagnosis were significant worse prognostic factors for unplanned hospitalization. Conclusions: The OS in the elderly metastatic CRC patients was good and similar to the general population with this disease. The number of CIRS-G level 4 comorbidities was associated with worse OS but no specific CIRS-G category was individually associated with OS.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15729-e15729
Author(s):  
Michael Shusterman ◽  
Erin Jou ◽  
Andreas Kaubisch ◽  
Jennifer W. Chuy ◽  
Lakshmi Rajdev ◽  
...  

e15729 Background: The neutrophil to lymphocyte ratio (NLR), a marker of systemic inflammatory response, has been suggested as a prognostic marker in patients with pancreatic adenocarcinoma (PAC). Black and Hispanic patients have been underrepresented in studies evaluating the significance of NLR in PAC. We investigated the prognostic significance of NLR in patients with advanced PAC treated at the Montefiore-Einstein Center for Cancer Care (MECCC) in the Bronx, NY. Methods: We included patients who were chemotherapy naive and treated for unresectable or metastatic PAC at MECCC between 2006 and 2015. Demographics, clinical characteristics and treatment data were collected. Overall survival was determined by the Kaplan-Meier method and Cox proportional-hazards models were built to assess survival differences adjusting for clinically relevant and statistically significant variables. Results: 201 patients were included in the study. Median age was 65 (range 32, 90). 52% were male. 41 were White (19%), 71 Black (33%), 71 Hispanic (33%), and 33 Other (15.3%). 66 (30.6%) had unresectable disease and 135 (62.5%) metastatic disease. An NLR ≥ 4 was associated with a worse OS compared to an NLR ≤ 4 (median 10 vs. 16.4 months; HR 1.895; 95% CI 1.390, 2.585; P < 0.0001). Predictors of worse OS on univariate analysis were ever smoker status (HR 1.365; P = 0.05), metastatic disease (HR 1.736; P = 0.001), and albumin ≤ 3.5 g/dL (HR 2.558; P< 0.0001). An NLR ≥ 4 on multivariate analysis remained significantly associated with worse OS (HR 1.665; 95% CI 1.188, 2.334; P = 0.003) after adjusting for age, gender, ever smoker status, metastatic disease, and albumin. Conclusions: In a cohort with significant minority patient representation, an NLR ≥ 4 was associated with significantly worse overall survival in patients with advanced pancreatic cancer. An elevated NLR in advanced PAC may be an important independent predictor to risk stratify patients and predict poor OS in future analyses.


2003 ◽  
Vol 21 (19) ◽  
pp. 3638-3646 ◽  
Author(s):  
Peter Jantscheff ◽  
Luigi Terracciano ◽  
Adam Lowy ◽  
Katharina Glatz-Krieger ◽  
Fritz Grunert ◽  
...  

Purpose: CEACAM6, CEACAM1, and human carcinoembryonic antigen (CEA) are coexpressed in normal colorectal epithelia, but show deregulated expression in colorectal cancers (CRC). Upregulation of CEACAM6 expression in hyperplastic polyps and early adenomas represents one of the earliest observable molecular events leading to colorectal tumors. The aim of our study was to evaluate the prognostic relevance of CEACAM6, CEACAM1, and CEA tissue expression in patients with CRC. Patients and Methods: Immunohistochemical analysis was carried out on tissue microarrays from 243 paraffin-embedded biopsies from a randomized controlled clinical trial (Swiss Group for Clinical Cancer Research [SAKK] 40/81) of adjuvant fluorouracil-based chemotherapy with CEACAM-specific monoclonal antibodies. The median follow-up was 8 years. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan-Meier estimates and hazard ratios (HRs) estimated using Cox proportional hazards models. Results: Tissue expression of CEACAM6, CEACAM1, and CEA was enhanced in 55%, 58%, and 94% of patients, respectively. Multivariate Cox analysis including sex, age, tumor site, stage, differentiation grade, treatment, and nodal status as covariates showed that CEACAM6 overexpression independently predicted poor OS (HR, 1.86; P = .0100) and DFS (HR, 2.00; P = .0028), whereas CEACAM1 or CEA were not significantly related to these outcomes. The data did not provide evidence for or against the hypothesis that the CEACAM6 effect on survival differs according to treatment. Conclusion: Expression of the cell adhesion molecule CEACAM6 in CRC is an independent prognostic factor allowing subdivision of patients into low- and high-risk groups. Whether CEACAM6 or CEA and CEACAM1 might be useful as predictive markers of chemotherapy benefit remains unclear.


2021 ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Soo Min Son ◽  
Eun Ju Park ◽  
Sang Yeoup Lee ◽  
Jungin Choi ◽  
...  

Abstract Background: Colorectal cancer (CRC) is a malignant tumor of the large intestine. Studies have shown that the development and prognosis of CRC are associated with altered lipid metabolism. Niemann-Pick C1-Like 1 (NPC1L1), the target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, the role of altered NPC1L1 expression in the development and prognosis of CRC has not yet been determined.Methods: Datasets of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) database. To compare the expression of NPC1L1 in normal and CRC tissues, datasets obtained from the GDAC platform were used. To support these results, we also analyzed other datasets from the Gene Expression Omnibus (GEO) database. Student’s t-test and chi-square test were used for the analyses. The log-rank test and multivariate Cox proportional hazards regression analysis were performed to determine whether NPC1L1 is a significant factor affecting the prognosis of CRC.Results: The mRNA expression of NPC1L1 was found to be upregulated in CRC, and was significantly associated with the N- and pathological stages, but not with the histological type, age, and sex. Moreover, an increase in NPC1L1 expression in CRC was associated with poorer survival, based on the Kaplan–Meier and multivariate regression analyses.Conclusions: High expression of NPC1L1 is associated with CRC development, pathological stage, and prognosis. The present study suggests that NPC1L1 represents a potential independent prognostic marker for CRC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17040-e17040
Author(s):  
Tao Qin ◽  
Hao Yu ◽  
Bo Wang ◽  
Cui Tan ◽  
Huangming Hong ◽  
...  

e17040 Background: PD-1/PD-L1 blockade significantly improved survival for bladder cancer. PD-L1 expression might not be an ideal marker for patient selection in isolation. Several studies demonstrated that alternative markers such as NLR, a biomarker of systemic inflammation response to therapy, correlated with outcomes in a variety of cancers including bladder cancer, might be a predictor for patient selection and the response to immunotherapy. However, no reporters have been made combination of NLR and PD-L1 in predicting prognosis in bladder cancer. Methods: Suitable tissue of 100 FFPE blocks of bladder cancer patients treated in Sun Yat-Sen Memorial Hospital Sun Yat-sen University were stained with PD-L1 antibody. Clinicopathological data and pretreatment complete blood count were retrospectively collected. All patients were classified into high NLR group and low NLR group at cut-off 3.0. Kaplan-Meier and Cox proportional hazard models analyses were used to assessed the predictor of combined PD-L1/NLR for disease-free survival (DFS) and overall survival (OS). Results: Patients were mostly male (79%) with high grade () lymph node positive (21%), T3-4 (33%) . The positivity of PD-L1 expression was 22% (22/100) at cut-off 1%. Univariate analysis showed that PD-L1 expression was positively associated with larger tumor size, higher grade, positive lymph node metastases. Median DFS and OS were 35 months and 37 months, respectively. Both PD-L1 expression and NLR were associated with DFS and OS. COX analysis model showed that PD-L1 and NLR were independent prognostic factors for tumor prognosis. Of interest, when patients were divided in two groups based on PD-L1/NLR: patients with PD-L1+/high NLR as group 1 and other patients as group 2, group1 had significantly shorter DFS and OS (DFS, X2 = 4.146, P = 0.042; OS, X2 = 10.274, P = 0.001). COX proportional hazards regression models indicated that PD-L1+/high NLR was correlated with a significantly shorter DFS and OS (DFS, hazard ration [ HR] = 2.572, P = 0.05; OS, HR = 3.811, P = 0.003). Conclusions: The study indicated that combined use of PD-L-1/ NLR as predictive biomarker for survival. This feasible panel may be optional maker applied to select patients for immunotherapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yangyang Qian ◽  
Zongfu Pan ◽  
Zhenying Guo ◽  
Xinyang Ge ◽  
Guowan Zheng ◽  
...  

Objectives. Many patients with papillary thyroid cancer (PTC) have a high recurrence risk and poor prognosis, and the main obstacle to the clinical diagnosis and treatment of PTC is lack of effective predictive molecular markers. The purpose of this study was to investigate the clinicopathological and prognostic implications of WW domain binding protein 5 (WBP5) expression in PTC. Materials and Methods. Immunohistochemistry of WBP5 was performed using tissue microarrays of 131 patients with PTC who underwent surgery during January 2006 and January 2010 in the Zhejiang Cancer Hospital. Statistical analyses were conducted to evaluate the association between WBP5 expression and the clinicopathological features and to analyze the disease-free survival (DFS) and prognostic factors. Results and Conclusion. The positive expression rate of WBP5 in PTC and the adjacent normal tissues was 42.75% (56/131) and 45.45% (10/22), respectively. WBP5 expression was significantly correlated with bilaterality, capsule invasion, and N-stage, and it was a favorable factor of DFS. Moreover, patients with a high WBP5 expression exhibited reduced risk of disease recurrence compared with that in patients with low WBP5 expression in the univariate analysis, whereas the multivariate analysis suggested that WBP5 was not an independent prognostic factor. Our results indicate that WBP5 might be a favorable prognosis indicator of PTC.


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