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.

MiR-485-5p as a potential biomarker and tumor suppressor in human colorectal cancer

2020 ◽  
Vol 14 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Yuqin Pan ◽  
Jian Qin ◽  
Huiling Sun ◽  
Tao Xu ◽  
Shukui Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Cox Regression ◽  
Roc Curves ◽  
Functional Study ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Polymerase Chain

Aim: To investigate the role of miR-485-5p in colorectal cancer (CRC). Methodology: The level of miR-485-5p in serum and cell lines were measured by quantitative real-time polymerase chain reaction, and analyzed the diagnostic and prognostic value. Additionally, the biological effect of miR-485-5p on CRC cells was also explored in vitro. Results: The receiver operating characteristic (ROC) curves analysis revealed that miR-485-5p was a diagnostic candidate. Kaplan-Meier analyses demonstrated that patients with low serum miR-485-5p had shorter overall survival. In addition, the result of cox regression model indicated that miR-485-5p was not an independent risk factor for progression. Functional study revealed that overexpression of miR-485-5p could inhibit CRC cell proliferation, invasion and facilitates cell apoptosis. Conclusion: Our study revealed that miR-485-5p was a tumor suppressor and it could serve as a potential prognostic biomarker in CRC.

scholarly journals The Development of Three-DNA Methylation Signature as a Novel Prognostic Biomarker in Patients with Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shu Gong ◽  
Weijian Ye ◽  
Tiankai Liu ◽  
Shaofen Jian ◽  
Wenhua Liu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Methylation Array ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
And Gender

Aims. The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients. Methods. The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database. These patients were divided into training and validation datasets. A risk score model was established based on Kaplan-Meier and multivariate Cox regression analysis of training cohort and tested in validation cohort. Results. Among total 14,626 DNA methylation candidate markers, we found that a three-DNA methylation signature (NR1H2, SCRIB, and UACA) was significantly associated with overall survival of CRC patients. Subgroup analysis indicated that this signature could predict overall survival of CRC patients regardless of age and gender. Conclusions. We established a prognostic model consisted of 3-DNA methylation sites, which could be used as potential biomarker to evaluate the prognosis of CRC patients.

The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽  
2021 ◽  
Author(s):  
Peng Wang ◽  
Chen Luo ◽  
Peng-jie Hong ◽  
Wen-ting Rui ◽  
Shuai Wu
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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.

Prognostic Factors Associated with Outcomes in Small Bowel Neuroendocrine Tumors

2017 ◽  
Vol 83 (10) ◽  
pp. 1174-1178 ◽  
Author(s):  
Nicholas Manguso ◽  
Jeffrey Johnson ◽  
Attiya Harit ◽  
Nicholas Nissen ◽  
James Mirocha ◽  
...  
Keyword(s):  
Small Bowel ◽  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Open Operation ◽  
Recurrence Group

Small bowel neuroendocrine tumors (SBNET) account for most gastrointestinal neuroendocrine tumors. Patients often present with late-stage disease; however, there is little information regarding factors that contribute to recurrence. Database review identified 301 patients diagnosed with SBNET between 1990 and 2013. Univariate analysis included patients who underwent complete resection. Survival was estimated by the Kaplan–Meier method. A total of 147 patients met study criteria. Average age was 60 years (range 21–91); 49 per cent were male. Thirty-seven (25.3%) patients had laparoscopic resection, and 29 (19.9%) patients had only small bowel disease, whereas 108 (72.6%) had nodal metastasis. Five-year overall and disease-free survival were 97.5 and 73.5 per cent. Forty-seven (32%) patients had recurrence. The recurrence group was more likely to have an open operation (59.6 vs 32%, P < 0.01), mesenteric invasion, or lymphatic metastasis (87.2 vs 67%, P < 0.01) compared with the no-recurrence group. Cox regression analysis showed that variables associated with recurrence included nodal disease (HR 9.06, P = 0.03), lymphovascular invasion (LVI) (3.95, P < 0.01), perineural invasion (PNI) (3.48, P < 0.01), and mesenteric involvement (3.77, P = 0.03). Patients with SBNET presenting with nodal metastasis, mesenteric involvement, LVI, or PNI have a higher risk of recurrence. Closer surveillance should be considered after operative resection.

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.

Adjuvant chemotherapy (ACT) in stage II colon cancer (CC) in patients with Lynch syndrome.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3550-3550
Author(s):  
Karsten Schulmann ◽  
Sven Koepnick ◽  
Christoph Engel ◽  
Christiane Bernhardt ◽  
Verena Steinke ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Regression Analyses ◽  
Free Survival ◽  
Kaplan Meier ◽  
Stage Ii Colon Cancer ◽  
Disease Free

3550 Background: Previous studies showed conflicting results regarding the value of ACT in MSI-H CC. A recent study reported differential benefits from 5-FU-based ACT comparing suspected sporadic vs suspected hereditary MSI-H CC. We sought to evaluate the prognostic impact of ACT in a large cohort of Lynch syndrome (LS) patients (pts) with stage II CC. Methods: To minimize selection bias diagnoses >2 years prior to registration in the database of the German HNPCC consortium were excluded. 278 patients (61% male, mean age 42.9y, 13% stage IIB, 51% with MMR gene mutation) were eligible. Overall Survival (OS), CC-specific Survival (CSS), and Disease Free Survival (DFS) were analyzed using Kaplan-Meier and Cox Regression analyses. Results: 5y OS, CSS and DFS were 95%, 95% and 93% respectively. Right-sided CC was independently associated with lower DFS in stage II and IIA. Increasing age was associated with lower OS, CSS and DFS in stage IIA, however we observed only trends in the multivariate analysis. Surgery alone (without ACT) was associated with a slightly lower OS in stage IIA (univariate HR 3,659; 95% CI 0,81-16,5; P=0.092); but not with lower DFS and CSS. Prognosis was not different comparing FOLFOX vs. 5-FU-based ACT. Conclusions: Our data suggest that LS pts with stage II CC do not benefit from ACT. FOLFOX was not superior to 5-FU-based ACT. If our results are confirmed, LS pts with stage IIA CC should not receive ACT. The group of stage IIB CC was too small to make definite conclusions. [Table: see text]

Micrometastasis volume in stage II colorectal cancer: A prospective study by Clinical Study Group of Osaka University (CSGO).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 597-597
Author(s):  
Kohei Murata ◽  
Hirofumi Yamamoto ◽  
Mutsumi Fukunaga ◽  
Tadashi Ohnishi ◽  
Shingo Noura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Stage Ii ◽  
Significant Prognostic Factor ◽  
Rt Pcr ◽  
Clinical Value ◽  
Poor Prognostic Factor ◽  
Stage Ii Colorectal Cancer ◽  
Cea Mrna

597 Background: We reported in a retrospective study that the presence of micrometastasis in lymph nodes (LNs), when assessed by CEA-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer (CRC). The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Methods: From November 2001 to December 2005, a total of 419 CRC cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II CRC were enrolled. After RNA quality check, 304 CRC cases were analyzed for CEA mRNA in LNs by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Post-operative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-FU derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for one year, while chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (High-MMV, n = 95) was an independent poor prognostic factor for 5-year DFS ( P= 0.001) and 5-year OS ( P= 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II CRC.

Predictors of recurrence in patients with surgically resected pancreatic neuroendocrine tumors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 408-408
Author(s):  
Cynthia Harris ◽  
Michelle Kang Kim ◽  
Kiwoon Joshua Baeg ◽  
Mi Ri Lee ◽  
Julie Starr ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Disease Recurrence ◽  
Stage Ii ◽  
Pancreatic Neuroendocrine Tumors ◽  
Cox Regression Analysis ◽  
Grade 3

408 Background: Current surveillance guidelines regarding follow up of patients with resected pancreatic neuroendocrine tumors (PNETs) are based on limited data, and there have been few studies evaluating recurrence risk in such patients. We assessed disease-free survival (DFS) in a large, multi-institutional cohort of patients with resected PNETs. Methods: Patients with surgically resected, non-metastatic PNETs between 1990-2017 were identified using institutional databases at three institutions: Mount Sinai Hospital, Dana-Farber Cancer Institute, and University of Pennsylvania. Recurrence date was defined as the imaging date documenting first recurrence (n = 56); if an imaging date was not available, then July 1 of that year was used in calculations (n = 9). Kaplan-Meier analysis was used to estimate DFS; multivariate Cox regression analysis was used to assess DFS adjusted for patient and disease-related characteristics, including tumor stage and grade. Results: We identified a total of 418 patients with surgically resected, non-metastatic PNETs between 1990-2017. Of these patients, 299 patients had complete stage and tumor grade information and were used for subsequent analysis. Patients were 48.6% male with a median age of 57.5 years at time of surgery. The distribution of AJCC stage and grade was as follows: 170 (56.9%) patients were stage I, 129 (43.1%) were stage II; 167 (55.9%) had grade 1, 121 (40.5%) had grade 2, and 11 (3.7%) had grade 3 tumors. Median follow-up was 2.6 years (interquartile range = 4.2); during this time, 65 (21.7%) patients developed disease recurrence. After adjusting for potential confounders, patients with more advanced stage and higher tumor grade were significantly more likely to develop disease recurrence (Hazard Ratio (HR): 6.9, 95% CI: 2.5-19.1 for stage II; HR 4.0 (1.7-9.5) for grade 2; HR 2.6 (0.4-17.8) for grade 3). Both higher stage and tumor grade were associated with decreased DFS (p < 0.0001 for both). Conclusions: In surgically resected PNETs, with a median follow-up time of 2.6 years, both higher stage and higher grade are associated with decreased DFS. Further follow up of this cohort is planned.

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.

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