scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Chi Square ◽  
Interacting Protein ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

scholarly journals Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1922 ◽  
Author(s):  
Jianhong Peng ◽  
Yongchun Wang ◽  
Rongxin Zhang ◽  
Yuxiang Deng ◽  
Binyi Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Immune Cell ◽  
Cox Regression ◽  
Simultaneous Detection ◽  
Prognostic Index ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Prognostic Information ◽  
Kaplan Meier

Background: A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO) after liver metastasectomy. Methods: Simultaneous detection of the immune constituents CD3+, CD8+, Foxp3+ T, and α-SMA+ cells in the liver oligometastasis of 133 patients was conducted using a four-colour immunohistochemical multiplex technique. Immune cells were quantified, and tumour-infiltrating lymphocyte (TIL) ratios were subsequently calculated. Correlation analysis was performed using Pearson’s correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analysed using the Kaplan–Meier method and Cox regression models. Results: Significantly fewer CD3+, CD8+, and Foxp3+ T cells were observed in the intratumoural region than in the peritumoural region of liver metastases. CD3+, CD8+, Foxp3+ T, and α-SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. Only the CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p < 0.001). Patients with high intratumoural CD8/CD3 ratios had significantly longer 3-year RFS (59.0% vs. 47.4%, p = 0.035) and 3-year OS rates (83.3% vs. 65.8%, p = 0.007) than those with low intratumoural CD8/CD3 ratios. Multivariate analyses revealed that the intratumoural CD8/CD3 ratio was independently associated with RFS (HR = 0.593; 95% CI = 0.357–0.985; p = 0.043) and OS (HR = 0.391; 95% CI = 0.193–0.794; p = 0.009). Conclusion: These findings offer a better understanding of the prognostic value of immune cell infiltration on liver oligometastasis from colorectal cancer.

Prognostic impact of tumor-associated B cells and plasma cells in colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 587-587
Author(s):  
Jonna Berntsson ◽  
Bjorn Nodin ◽  
Jakob Eberhard ◽  
Karin Jirstrom
Keyword(s):  
Colorectal Cancer ◽  
B Cell ◽  
Immune Cell ◽  
Multivariable Analysis ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Cd20 Expression ◽  
Incident Cases ◽  
The Impact

587 Background: Multiple studies have described associations between infiltrating immune cells, prognosis and treatment response in cancer. However, the clinical relevance has most often been attributed to the T-cell linage, whereas the humoral immune response is less investigated. In colorectal cancer (CRC), accumulation of CD20-positive B lymphocytes at the advancing margin of metastatic CRC has been demonstrated to correlate with prolonged survival. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in colorectal cancer (CRC). Methods: Immunohistochemical expression of CD20 and CD138 in was analyzed in tissue microarrays with tumors from 557 incident cases of CRC from the Malmö Diet and Cancer Study, a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20 and CD138 expression on 5-year overall survival (OS). Results: CD20 expression could be evaluated in 549 (98.6 %) cases and CD38 in 534 (95.9 %) cases. CD20 expression correlated significantly with both immune cell-specific and tumor-specific expression of CD138 (p < 0.001 and p = 0.001, respectively). Furthermore, immune cell-specific CD20 and CD138 expression as well as tumor-specific CD138 expression correlated significantly with lower T-stage (p < 0.001, p < 0.001 and p = 0.002, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.66, 95 % CI 0.50-0.86), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.65; 95% CI 0.48-0.90). Neither immune cell nor tumor cell-specific CD138 expression was significantly associated with prognosis. Conclusions: Our results demonstrate that increased B cell infiltration in CRC is an independent factor of improved prognosis. Moreover, the study provides a first demonstration of the expression and clinicopathological correlates of immune cell-specific CD138 expression in CRC, thus providing a further characterization of the immune landscape in this type of cancer.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

Expression and Clinical Significance of Serum Exosomal miR-375 in Patients with Gastric Cancer

2021 ◽  
Vol 7 (5) ◽  
pp. 3896-3904
Author(s):  
Daoting Deng ◽  
Hong Zhang ◽  
Junxi Liu ◽  
Lina Ma ◽  
Xinrui Lei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Healthy Group ◽  
Cancer Group ◽  
Kaplan Meier ◽  
Gastric Cancer Patients ◽  
Gastric Cancer Group

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.

Abnormal Serum Free Light Chain Ratios Are Associated with Earlier Time to First Treatment and Poor Survival in Patients with Chronic Lymphocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3141-3141
Author(s):  
Guy Pratt ◽  
Graham Mead ◽  
Supratik Basu ◽  
Abe Jacobs ◽  
Roger Holder ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Female Ratio ◽  
Cox Regression Analysis ◽  
Serum Free ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Time To First Treatment

Abstract Introduction: Serum free light chains (sFLC) have prognostic significance in plasma cell disorders. In B-cell chronic lymphocytic leukemia (CLL), a small study found 8/18 (44%) of patients to have abnormal FLC ratios but no assessment of prognostic value was published. The aim of the present study was to determine whether abnormal serum FLC concentrations are indicative of a poor prognosis in CLL patients. Methods: Sera were analysed from 381 previously diagnosed CLL patients (Stage A 307; B 30; C 26; 18 missing; male: Female Ratio 1.6:1, mean age 71 (29–98)) with samples taken before their first treatment (303) or after treatment (78). The study was approved by the Birmingham Heart of England NHS Trust Review Board. Patients were described using the Binet staging system and measured for prognostic markers including CD38, Zap70, mutational status, β2M and FLC. Kaplan Meier survival curves and Cox proportional hazards regression (age, sex, CD38, Zap 70, mutational status, β2M and sFLC) were calculated using SPSS v14. Results: 147/381 (39%) patient sera had abnormal sFLC ratios. Kaplan Meier analysis of all deaths showed abnormal ratios were significantly associated with worse survival (n=350, p&lt;0.001). Analysis of deaths attributed to CLL (n=30) also indicated that an abnormal FLC ratio was predictive of shorter survival (p=0.001). However, for deaths not attributed to CLL (n=32), the FLC ratio was not significantly predictive of outcome (p=0.112). For Cox regression analysis (n=228) of deaths attributed to CLL only, three significant, independent, prognostic factors were identified: CD38 (p&lt;0.001), abnormal ratio (p&lt;0.001) and Stage (p=0.027). Analysis of the untreated patient population (n=303), using Kaplan Meier analysis of time to first treatment, found that an abnormal lambda ratio (p=0.04) but not an abnormal kappa ratio (p=0.443) predicted earlier treatment. For patients with an abnormal lambda ratio, the mean time to first treatment was 38 months earlier than those patients with a normal ratio. Cox regression analysis (n=171) of time to first treatment, found 4 significant, independent factors predicting earlier treatment: Zap70 (p&lt;0.001), Age (p&lt;0.001), abnormal sFLC ratio (p=0.001) and Stage (p=0.027). Conclusions: As shown in other monoclonal gammopathies, abnormal sFLC ratios were associated with poorer outcomes in patients with CLL. Furthermore, in an untreated population, patients with an abnormal lambda sFLC ratio required earlier treatment, indicating a pathological mechanism which is as yet unclear but which warrants further investigation.

scholarly journals Up-Regulation of Long Noncoding RNA CCAL Predicts Poor Patient Prognosis and Promotes Tumor Metastasis in Osteosarcoma

2017 ◽  
Vol 32 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Da-Kai Zhou ◽  
Xi-Wang Yang ◽  
Huining Li ◽  
Yongbo Yang ◽  
Zhen-Jun Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Tumor Metastasis ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Patient Prognosis ◽  
Invasion Assays

Background Long noncoding RNAs (IncRNAs) play essential roles in tumor progression. Aberrant colorectal cancer-associated IncRNA (CCAL) has been found in colorectal cancer. However, the function of IncRNA CCAL in osteosarcoma (OS) remains unclear. Methods Quantitative real-time PCR (qRT-PCR) was performed to measure CCAL expression in OS tissues and adjacent nontumor tissues. The correlation betweent CCAL expression and clinicopathological features and prognosis was also analyzed. In addition, the function of CCAL was further evaluated by cell proliferation, migration and invasion assays. Results We showed that CCAL was significantly up-regulated in OS tissues compared with adjacent nontumor tissues. Increased expression of CCAL was correlated with advanced TNM stage and metastasis. Kaplan-Meier analysis demonstrated that patients with high CCAL expression had lower overall survival than those with low CCAL expression. Multivariate Cox regression analysis indicated that CCAL expression might be an independent prognostic factor for OS patients. In addition, functional assays showed that decreased CCAL expression could inhibit OS cell proliferation, migration and invasion ability. Conclusions Our findings suggested that CCAL plays critical roles in OS progression and could act as a therapeutic target in the treatment of OS.

Expression of MUM1/IRF4 correlates with clinical outcome in patients with B-cell chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4671-4675 ◽  
Author(s):  
Chung-Che Chang ◽  
Jennifer Lorek ◽  
Daniel E. Sabath ◽  
Ying Li ◽  
Christopher R. Chitambar ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Interferon Regulatory Factor 4 ◽  
Cell Chronic Lymphocytic Leukemia

In this study, we evaluated the prognostic significance of multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) expression in B-cell chronic lymphocytic leukemia (B-CLL). Our results demonstrated that the absence of MUM1/IRF4 expression showed the highest relative risk among the factors analyzed in determining the probability for death in patients with B-CLL using univariate and multivariate Cox regression analysis. Patients without MUM1/IRF4 expression had significantly worse overall survival than did those with MUM1/IRF4 expression (52% cumulative survival, 63 months vs not reached, Kaplan-Meier survival analysis; P < .03, log-rank test). Patients with MUM1/IRF4 expression were more likely to have disease at low Rai stage and interstitial/nodular marrow involvement. Furthermore, only 1 of 11 patients with MUM1/IRF4 expression and interstitial/nodular marrow involvement died during a 100-month follow-up. Our results suggest that B-CLL with expression of MUM1/IRF4, indicative of postgerminal center origin, has a more favorable clinical course and that MUM1/IRF4 is an important prognostic marker in B-CLL.

scholarly journals High Expression of PXN Predicts a Poor Prognosis in Acute myeloid leukemia

2021 ◽  
Author(s):  
xinwen zhang ◽  
Hao Xiong ◽  
Jialin Duan ◽  
Xiaomin Chen ◽  
Yang Liu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Receive Treatment ◽  
To Receive ◽  
Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is one of the common malignant diseases of hematopoietic system. Paxillin ( PXN ) is an important part of focal adhesions (FAs), which is related to the poor prognosis of many kinds of malignant tumors. However, no research has focused on the expression of PXN in AML. We aimed to investigate the expression of PXN in AML and its prognostic significance. Methods: Using GEPIA and UALCAN database to analyze the expression of PXN in AML patients and its prognostic significance. Bone marrow samples of newly diagnosed AML patients were collected to extract RNA, and qRT-PCR was used to detect the expression of PXN . The prognosis was followed up. Chi-square test was used to analyze the relationship between PXN expression and clinical laboratory characteristics. Kaplan-Meier analysis was used to draw survival curve, and Cox regression analysis was used to analyze the independent factors affecting the prognosis of patients with AML. The co-expression genes of PXN were analyzed by LinkedOmics to explore its biological significance in AML. Results: Kaplan-Meier analysis showed that the overall survival time of AML patients was related to whether to receive treatment and PXN expression(P<0.05). COX regression analysis showed that whether to receive treatment (HR=0.227，95%CI=0.075-0.689， P =0.009) and high expression of PXN (HR=4.484，95%CI=1.449-13.889， P =0.009) were independent poor prognostic factors in patients with AML. Conclusion: PXN is highly expressed in AML patient, and high PXN expression is an indicator of poor prognosis in AML patient.

scholarly journals LINC01268 and CTB-31O20.2 as Prognostic and Functional Protective Immune Related lncRNAs in Glioblastoma

2021 ◽  
Author(s):  
Dong-Hui Liu ◽  
Xiu Yang ◽  
Han Meng ◽  
Gui Yun Zhang ◽  
Shanghang Shen
Keyword(s):  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
Competitive Endogenous Rnas ◽  
The Central Nervous System ◽  
And Migration ◽  
Immune Related Genes

Abstract Glioblastoma (GBM) is the most common and deadly tumor in the central nervous system. Recent studies illuminated that long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) and play an important role in GBM by regulating immune responses. Here, GBM datasets from TCGA database were analyzed to obtain 356 significantly differentially expressed lncRNAs (DE-lncRNAs), 4951 DE-mRNAs, and 34 DE-miRNAs in GBM, respectively. For mRNAs, 369 DE-mRNAs were identified as immune-related genes in Immport database. For DE-lncRNAs, univariate analysis identified 39 DE-lncRNAs with prognostic significance, and 9 DE-lncRNAs are included in ImmLnc database. Then, combined analysis was conducted, by integrating 9 immune related DE-lncRNAs, 369 immune related DE-mRNAs and 34 DE-miRNAs, and generated a ceRNA network composed of 2 upregulated lncRNAs (LINC01268 and CTB-31O20.2), 3 downregulated miRNAs and 5 upregulated mRNAs. Then we focused on LINC01268 and CTB-31O20.2, and Kaplan-Meier survival, univariate and multivariate Cox regression analysis showed that LINC01268 and CTB-31O20.2 serve as independent protective prognostic markers in GBM. Finally, LINC01268 and CTB-31O20.2 overexpression was conducted in GBM cell U251. CCK8, transwell and scratch healing assay indicated that LINC01268 and CTB-31O20.2 inhibits GBM cell line U251 proliferation, invasion and migration. To sum up, LINC01268 and CTB-31O20.2 are independent prognostic immune related markers, and reduces cancer cell proliferation and metastasis in GBM.

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