Toll-like receptor 3 is a potential prognosis marker and associated with immune infiltration in stomach adenocarcinoma

2021 ◽  
pp. 1-17
Author(s):  
Zhihao Huang ◽  
Aoxiao He ◽  
Jiakun Wang ◽  
Hongcheng Lu ◽  
Xiaoyun Xu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Positive Association ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Qrt Pcr ◽  
Tlr3 Expression ◽  
Immune Biomarkers ◽  
Prognosis Marker

BACKGROUND: Toll-like receptors participate in various biological mechanisms, mainly including the immune response and inflammatory response. Nevertheless, the role of TLRs in STAD remains unclear. OBJECTIVE: We aimed to explore the expression, prognosis performance of TLRs in STAD and their relationship with immune infiltration. METHODS: Student’s t-test was used to evaluate the expression of TLRs between STAD tissues and normal tissues. Kaplan-Meier method was applied to explored the prognosis value of TLRs in STAD. And qRT-PCR validated their expression and prognosis value. Spearman’s correlation analysis and Wilcoxon rank-sum test were used to assess the association between TLRs and immune infiltration in STAD. RESULTS: The mRNA level of TLR3 was downregulated in STAD. We summarized genetic mutations and CNV alteration of TLRs in STAD cohort. Prognosis analysis revealed that STAD patients with high TLR3 expression showed better prognosis in OS, FP and PPS. The result of qRT-PCR suggested that TLR3 expression was decreased in STAD tissues and STAD patients with high TLR3 mRNA level had a better OS. Univariate and multivariate cox regression analysis suggested TLR3 expression and clinical stage as independent factors affecting STAD patients’ prognosis. A positive association existed between TLR3 expression and the abundance of immune cells and the expression of various immune biomarkers. Furthermore, key targets related to TLR3 were identified in STAD, mainly including MIR-129 (GCAAAAA), PLK1, and V$IRF1_01. CONCLUSIONS: Our result demonstrated TLR3 as a prognosis marker and associated with immune infiltration in STAD.

scholarly journals CILP2 overexpression predicts poor prognosis in colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

Abstract Background Cartilage Intermediate Layer Protein 2 (CILP2), a glycoprotein with mutations associated with abnormal blood lipid concentrations in normal and cardiovascular diseases patients, was barely reported with clinical features of tumors. We evaluated the role of CILP2 among all stages and histology in colorectal cancer (CRC) in the Cancer Genome Altas (TCGA), and furtherly verified using immunohistochemistry assay within human CRC tissues. Materials and methods Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and P value was calculated by log-rank test. Kaplan-Meier curves were tested by log-rank test. Results CILP2 was significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in TCGA cohort (P < 0.001) and in TMA cohort (P = 0.001). In addition, CILP2 high-expression was strongly correlated with T3/4 stage (P = 0.001), N1/2/3 stage (P = 0.005), M1 stage (P = 0.048), and higher clinical stage (UICC 2010 stage) (P < 0.001) in TCGA cohort, and also positively associated with T3/4 stage (P = 0.022) and higher clinical stage (UICC 2010 stage) (P = 0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor (P = 0.003). Conclusion We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer.

scholarly journals CILP2 overexpression correlates with tumor progression and predicts poor outcome in patients with colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Genetic Alterations ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

Abstract Background: Genetic alterations play an important role in the progression of colorectal cancer (CRC). Identifying new biomarkers to assess the prognosis of patients with colorectal cancer is critical. Cartilage Intermediate Layer Protein 2 (CILP2) gene, screened from the TCGA database by bioinformatics, may be closely related to the progression of colorectal cancer. CILP2 was barely reported with clinical features of tumors.Materials and methods: Clinical information and RNA-seq data were derived from the TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and the P-value was calculated by the log-rank test. Kaplan-Meier curves were tested by the log-rank test. Results: CILP2 was statistically significant higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in the TCGA cohort (P<0.001) and in the TMA cohort (P=0.001). Also, CILP2 high-expression was strongly correlated with T3/4 stage (P=0.001), N1/2/3 stage (P=0.005), M1 stage (P=0.048), and higher clinical stage (UICC 2010 stage) (P<0.001) in TCGA cohort, and also positively associated with T3/4 stage (P=0.022) and higher clinical stage (UICC 2010 stage) (P=0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor (P=0.003).Conclusion: We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer.

Tumor Stage After Neoadjuvant Chemotherapy Determines Survival After Surgery for Adenocarcinoma of the Esophagus and Esophagogastric Junction

2014 ◽  
Vol 32 (27) ◽  
pp. 2983-2990 ◽  
Author(s):  
Andrew R. Davies ◽  
James A. Gossage ◽  
Janine Zylstra ◽  
Fredrik Mattsson ◽  
Jesper Lagergren ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Tumor Stage ◽  
Response To Treatment ◽  
Cox Regression Analysis ◽  
Systemic Recurrence

Purpose Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable. Methods We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis. Results Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v 13%, respectively; P = .030) and systemic recurrence (19% v 29%, respectively; P = .027) and improved Mandard tumor regression scores (P < .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation. Conclusion The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

scholarly journals Identification and Validation of Immune-Related LncRNA Prognostic Signature for Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Guomin Wu ◽  
Qihao Wang ◽  
Ting Zhu ◽  
Linhai Fu ◽  
Zhupeng Li ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Clinical Features ◽  
Cox Regression ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Immune Infiltration

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.

Identification of the Pyroptosis-related Signature for Predicting Prognosis in Cervical Cancer

2021 ◽  
Author(s):  
Cankun Zhou ◽  
Chaomei Li ◽  
Yuhua Zheng ◽  
Xiaochun Liu
Keyword(s):  
Cervical Cancer ◽  
Tumor Microenvironment ◽  
Cox Regression ◽  
Experimental Studies ◽  
Risk Groups ◽  
Core Gene ◽  
Low Risk ◽  
Prognostic Signature ◽  
Cox Regression Analysis ◽  
Immune Infiltration

Abstract Background: Cervical cancer (CC) is one of the most common malignancies in gynecology. There is still a lack of specific biomarkers for the diagnosis and prognosis of CC. Pyroptosis is one of the methods of programmed cell death, and its various components are related to the occurrence, invasion, and metastasis of tumors. However, the role of pyroptosis in CC has not yet been elucidated.Methods: This study focuses on the development of a prognostic signature associated with pyroptosis for CC patients using integrated bioinformatics to elucidate the relationship between the signature and the tumor microenvironment and immune response.Results: We identified a prognostic signature based on eight pyroptosis-related genes (PRGs), with better prognostic survival in the low-risk group (P<0.05) and AUC values greater than 0.7. The results of the multi-factor Cox regression analysis indicated that the signature could be used as an independent prognostic factor, and both the DCA and the Nomogram suggested that the prognostic signature had good predictive power. Interestingly, this prognostic signature can also be applied to multiple tumors. In addition, the tumor microenvironment and immune infiltration status were significantly different between high and low-risk groups (P<0. 05). The core gene GZMB was screened and the CC-associated GZMB/ miR-378a/TRIM52-AS1 regulatory axis was constructed.Conclusion: The study successfully established the prognostic signature based on eight PRGs and reflected their tumor microenvironment and immune infiltration. The GZMB/ miR-378a/TRIM52-AS1 regulatory axis may play an important regulatory role in the development of CC, and further experimental studies are needed to validate these results subsequently.

scholarly journals Complex segmentectomy in the treatment of stage IA non-small-cell lung cancer

2019 ◽  
Vol 57 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Yoshinori Handa ◽  
Yasuhiro Tsutani ◽  
Takahiro Mimae ◽  
Yoshihiro Miyata ◽  
Morihito Okada
Keyword(s):  
Lung Cancer ◽  
Regression Analysis ◽  
Cancer Treatment ◽  
Cox Regression ◽  
Clinical Stage ◽  
Cancer Control ◽  
Cox Regression Analysis ◽  
Lung Cancer Treatment ◽  
Clinical Stage Ia ◽  
Stage Ia

AbstractOBJECTIVESAlthough segmentectomy for lung cancer has been widely accepted, complex segmentectomy, which creates several, intricate intersegmental planes, remains controversial. Potential arguments include risk of incurability and ‘failure of cancer control’. We compared the outcomes of complex segmentectomy versus lobectomy and evaluated its use in lung cancer treatment.METHODSWe retrospectively reviewed clinical stage IA lung cancer patients who underwent complex segmentectomy (n = 99) or location-adjusted lobectomy (n = 94) between April 2009 and December 2017. Clinicopathological and postoperative results were compared. Factors affecting survival were assessed by the Kaplan–Meier method and the Cox regression analysis.RESULTSNo significant differences were detected in 30-day mortality (0% vs 0%), overall complications (26.3% vs 21.3%) and prolonged air leakage (11.1% vs 9.6%) rates between the 2 groups, respectively. Comparable results were obtained for 5-year overall (93.5% vs 96.4%, respectively; P = 0.21) or recurrence-free (92.3% vs 88.5%, respectively; P = 0.82) survivals after complex segmentectomy or lobectomy. There were 2 (2.0%) recurrences after complex segmentectomy and 7 (7.5%) after lobectomy (P = 0.094), with 0 (0%) margin relapses in each group. Multivariable Cox regression analysis revealed that complex segmentectomy and lobectomy had a numerically similar impact on recurrence-free survival (hazard ratio 0.93, 95% confidence interval 0.32–2.69; P = 0.90).CONCLUSIONSComplex segmentectomy can provide acceptable short- and long-term outcomes in lung cancer treatment.

scholarly journals LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Longzhen Piao ◽  
Zhaoting Yang ◽  
Ying Feng ◽  
Chengye Zhang ◽  
Chunai Cui ◽  
...  
Keyword(s):  
Cox Regression ◽  
Transmembrane Protein ◽  
Small Cell Lung Carcinoma ◽  
Clinical Stage ◽  
Small Cell ◽  
Cancer Prognosis ◽  
Normal Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis ◽  
Potential Biomarker

Abstract Background Although the leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is one of the mitochondrial inner membrane proteins that is involved in cancer prognosis in various tumors, LETM1 as a biomarker for prognostic evaluation of non-small cell lung carcinoma (NSCLC) has not been well studied. Methods To address this issue, we used 75 cases NSCLC, 20 cases adjacent normal lung tissues and NSCLC cell lines. We performed immunohistochemistry staining and western blot analysis as well as immunofluorescence imaging. Results Our studies show that expression of LETM1 is significantly correlated with the lymph node metastasis (p = 0.003) and the clinical stage (p = 0.005) of NSCLC. The Kaplan-Meier survival analysis revealed that NSCLC patients with positive expression of LETM1 exhibits a shorter overall survival (OS) rate (p = 0.005). The univariate and multivariate Cox regression analysis indicated that LETM1 is a independent poor prognostic marker of NSCLC. In addition, the LETM1 expression is correlated with cancer stemness-related gene LGR5 (p < 0.001) and HIF1α expression (p < 0.001), but not with others. Moreover, LETM1 expression was associated with the expression of cyclin D1 (p = 0.003), p27 (p = 0.001), pPI3K(p85) (p = 0.025), and pAkt-Thr308 (p = 0.004). Further, our studies show in LETM1-positive NSCLC tissues the microvessel density was significantly higher than in the negative ones (p = 0.024). Conclusion These results indicate that LETM1 is a potential prognostic biomarker of NSCLC.

scholarly journals Analysis of Scoring Sequences in Matches of the Portuguese Premier League

2018 ◽  
Vol 64 (1) ◽  
pp. 255-263
Author(s):  
José M. Pratas ◽  
Anna Volossovitch ◽  
Ana I. Carita
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Cox Model ◽  
Positive Association ◽  
Descriptive Statistics ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Premier League ◽  
Chi Square Test

AbstractThe aim of this study was to examine the sequences of the first two goals scored in soccer matches in accordance with a range of different match contexts. Data from 1506 matches played in the Portuguese Premier League during six consecutive competitive seasons (2009-10 to 2014-2015) were analysed using descriptive statistics and the chi-square test in order to verify the association between variables and a Cox regression analysis was used to predict the time the second goal was scored in function of the time of the first goal scored in the match and the scoreline. The results revealed a higher frequency of the second goals being scored in the second half of a match (58%) and in the last 5 min periods of each half. A positive association was found for home teams and score-doubling goals (58%), as well as for away teams and score-equalizing goals (56%). For home and away teams the score-doubling goal of a match was strongly and positively associated with a win outcome for home (93%) and away teams (92%), while the score-equalizing goals were associated with a draw (home and away teams: 44%) and loss outcome (home: 33% and away teams: 32%). Finally, the Cox model showed that if the first goal was scored in the second half of the match, the probability of the second goal being scored was three times higher compared to the first half.

scholarly journals Identification and Validation of Prognostically Relevant Gene Signature in Melanoma

2020 ◽  
Vol 2020 ◽  
pp. 1-29
Author(s):  
Yali Gao ◽  
Yaling Li ◽  
Xueli Niu ◽  
Yutong Wu ◽  
Xiuhao Guan ◽  
...  
Keyword(s):  
Cox Regression ◽  
Gene Signature ◽  
Genomic Variation ◽  
Training Dataset ◽  
Validation Dataset ◽  
Multidimensional Data ◽  
Clinical Samples ◽  
Cox Regression Analysis ◽  
Qrt Pcr ◽  
Melanoma Patients

Background. Currently, effective genetic markers are limited to predict the clinical outcome of melanoma. High-throughput multiomics sequencing data have provided a valuable approach for the identification of genes associated with cancer prognosis. Method. The multidimensional data of melanoma patients, including clinical, genomic, and transcriptomic data, were obtained from The Cancer Genome Atlas (TCGA). These samples were then randomly divided into two groups, one for training dataset and the other for validation dataset. In order to select reliable biomarkers, we screened prognosis-related genes, copy number variation genes, and SNP variation genes and integrated these genes to further select features using random forests in the training dataset. We screened for robust biomarkers and established a gene-related prognostic model. Finally, we verified the selected biomarkers in the test sets (GSE19234 and GSE65904) and on clinical samples extracted from melanoma patients using qRT-PCR and immunohistochemistry analysis. Results. We obtained 1569 prognostic-related genes and 1101 copy-amplification, 1093 copy-deletions, and 92 significant mutations in genomic variants. These genomic variant genes were closely related to the development of tumors and genes that integrate genomic variation. A total of 141 candidate genes were obtained from prognosis-related genes. Six characteristic genes (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) were selected by random forest feature selection, many of which have been reported to be associated with tumor progression. Cox regression analysis was used to establish a 6-gene signature. Experimental verification with qRT-PCR and immunohistochemical staining proved that these selected genes were indeed expressed at a significantly higher level compared with the normal tissues. This signature comprised an independent prognostic factor for melanoma patients. Conclusions. We constructed a 6-gene signature (IQCE, RFX6, GPAA1, BAHCC1, CLEC2B, and AGAP2) as a novel prognostic marker for predicting the survival of melanoma patients.

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