scholarly journals Deciphering Promoter Hypermethylation of Genes Encoding for RASSF/Hippo Pathway Reveals the Poor Prognostic Factor of RASSF2 Gene Silencing in Colon Cancers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5957
Author(s):  
Marc Riffet ◽  
Yassine Eid ◽  
Maxime Faisant ◽  
Audrey Fohlen ◽  
Benjamin Menahem ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Hippo Pathway ◽  
Promoter Hypermethylation ◽  
Recurrence Free Survival ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Colon Cancers ◽  
Genes Encoding

The aims of this study were to assess the frequency of promoter hypermethylation of the genes encoding the Ras associated domain family (RASSF)/Hippo pathway, as well as the impact on overall (OS) and progression-free survival (PFS) in a single-center retrospective cohort of 229 patients operated on for colon cancers. Hypermethylation status was investigated by methylation-specific PCR on the promoters of the RASSF1/2, STK4/3 (encoding Mammalian Ste20-like protein 1 and 2 (MST1 and 2), respectively), and LATS1/2 genes. Clinicopathological characteristics, recurrence-free survival, and overall survival were analysed. We found the RASSF/Hippo pathway to be highly silenced in colon cancer, and particularly RASSF2 (86%). The other promoters were hypermethylated with a lesser frequency of 16, 3, 1, 10 and 6%, respectively for RASSF1, STK4, STK3, LATS1, and LATS2 genes. As the hypermethylation of one RASSF/Hippo family member was by no means exclusive from the others, 27% of colon cancers displayed the hypermethylation of at least two RASSF/Hippo member promotors. The median overall survival of the cohort was 60.2 months, and the median recurrence-free survival was 46.9 months. Survival analyses showed a significantly poorer overall survival of patients when the RASSF2 promoter was hypermethylated (p = 0.03). The median OS was 53.5 months for patients with colon cancer with a hypermethylated RASSF2 promoter versus still not reached after 80 months follow-up for other patients, upon univariate analysis (HR = 1.86, [95% CI: 1.05–3.3], p < 0.03). Such difference was not significant for relapse-free survival as in multivariate analysis. A logistic regression model showed that RASSF2 hypermethylation was an independent factor. In conclusion, RASSF2 hypermethylation is a frequent event and an independent poor prognostic factor in colon cancer. This biomarker could be investigated in clinical practice.

scholarly journals Prognostic Significance of Thrombocytosis in Node-negative Colon Cancer

2005 ◽  
Vol 33 (2) ◽  
pp. 228-235 ◽  
Author(s):  
EG Kandemir ◽  
A Mayadagli ◽  
B Karagoz ◽  
O Bilgi ◽  
O Turken ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Platelet Count ◽  
Prognostic Factor ◽  
Disease Free Survival ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Node Negative ◽  
The Impact ◽  
Disease Free

Several clinical studies have shown that thrombocytosis is a poor prognostic factor in some types of cancer, but data about the impact of thrombocytosis on prognosis in patients with colon cancer are very limited. We investigated the prevalence and prognostic effect of pre-operative thrombocytosis, defined as a platelet count > 400 × 109/l, retrospectively in patients with node-negative colon cancer. Out of 198 patients, 24 (12.1%) had thrombocytosis, and its presence correlated with tumour depth and lymphatic invasion. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with pre-operative thrombocytosis than those without thrombocytosis. On multivariate analysis, thrombocytosis alone retained significance as a poor prognostic factor for both disease-free survival and overall survival. In conclusion, this study shows an association between thrombocytosis and poor survival in patients with node-negative colon cancer. The pre-operative platelet count may help to identify patients with an unfavourable prognosis in this subgroup.

Blood and tumor inflammation markers in non-small cell lung cancer (NSCLC): Blood leukocytosis as an independent risk factor in early stage.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21110-e21110
Author(s):  
Andreas Carus ◽  
Morten Ladekarl ◽  
Henrik Hager ◽  
Hans Pilegaard ◽  
Patricia Switten Nielsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Stage I ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Elevated Blood ◽  
Blood Leukocytes ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Cancer Inflammation

e21110 Background: Cancer inflammation is associated with impaired survival in a range of cancers. We reviewed blood and intratumoral inflammatory markers in NSCLC. Methods: At the Departmentof Thoracic Surgery, Skejby Hospital, Aarhus, Denmark, consecutive patients with resected NSCLC from 2000 to 2008 were reviewed, and 906 patients with complete clinical data were identified. A subset of 341 consecutive patients, resected between 2003 and 2006, also had intratumoral CD66b+ neutrophils and CD163+ macrophages measured by immunohistochemistry and evaluated by stereological assessment. Results: A total of 526, 197, and 183 patients had stage I, II, and III, respectively. Multivariate analysis stratified for tumor stage revealed elevated blood leukocytes above upper limit of normal as a significant prognostic factor for recurrence-free survival (RFS)(hazard ratio [HR] 1.9; 95% CI 1.4-2.6; p<0.0001), cancer specific survival (CSS)(HR 1.9; 95% CI 1.4-2.7; p<0.0001), and overall survival (OS)(HR 1.5; 95% CI 1.1-1.9; p<0.006) in stage I NSCLC, but not in stage II and III. No prognostic impact of intratumoral neutrophils or macrophages was seen on CSS, RFS, or OS, neither in the entire cohort, nor limited to stage I patients with elevated blood leukocytes or with normal counts. Controlling intratumoral neutrophils and macrophages for localization restricted to tumor tissue, stromal tissue, or blood vessels, respectively, were also with no statistically significant difference. Conclusions: Blood leukocytosis is an independent prognostic factor for short recurrence free survival, cancer specific survival, and overall survival in stage I NSCLC, but not in stage II and III. However, intratumoral neutrophils or macrophages did not impact prognosis. Further studies are needed to elucidate the role of cancer inflammation in NSCLC.

Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

2009 ◽  
Vol 27 (28) ◽  
pp. 4709-4717 ◽  
Author(s):  
Hanne Krogh Jensen ◽  
Frede Donskov ◽  
Niels Marcussen ◽  
Marianne Nordsmark ◽  
Finn Lundbeck ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Independent Prognostic Factor ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Ca Ix

Purpose We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). Patients and Methods The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. Results The intratumoral neutrophils ranged from zero to 289 cells/mm2 tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX ≤ 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added. Conclusion The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

High ANKZF1 expression is associated with poor overall survival and recurrence-free survival in colon cancer

2019 ◽  
Vol 15 (18) ◽  
pp. 2093-2106 ◽  
Author(s):  
Xin Zhou ◽  
Yan-Na Shang ◽  
Ran Lu ◽  
Chuan-Wen Fan ◽  
Xian-Ming Mo
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Recurrence Free Survival ◽  
Poor Overall Survival ◽  
Free Survival

scholarly journals Association of preoperative anemia and perioperative allogenic red blood cell transfusion with oncologic outcomes in patients with nonmetastatic colorectal cancer

2019 ◽  
Vol 26 (3) ◽  
Author(s):  
H. Y. Kwon ◽  
B. R. Kim ◽  
Y. W. Kim
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Blood Transfusion ◽  
Oncologic Outcomes ◽  
Red Blood Cell Transfusion ◽  
Significant Prognostic Factor ◽  
Recurrence Free Survival ◽  
Preoperative Anemia ◽  
Free Survival

Background We investigated whether preoperative anemia and perioperative blood transfusion (pbt) are associated with overall survival and recurrence-free survival in patients with nonmetastatic colorectal cancer.Methods From 1 January 2009 to 31 December 2014, 1003 patients with primary colorectal cancer were enrolled in the study. Perioperative clinical and oncologic outcomes were analyzed based on the presence of preoperative anemia and pbt.Results Preoperative anemia was found in 468 patients (46.7%). In the anemia and no-anemia groups, pbt was performed in 44% and 15% of patients respectively. Independent predictors for pbt were preoperative anemia, higher American Society of Anesthesiologists score, laparotomy, lengthy operative time, advanced TNM stage, T4 stage, and 30-day morbidity. The use of pbt, but not preoperative anemia, was found to be an independent adverse prognostic factor for overall survival. In terms of recurrence-free survival, the presence of preoperative anemia was similarly not a significant prognostic factor, but the use of pbt was an independent factor for an unfavourable prognosis.Conclusions The use of pbt, but not preoperative anemia, was independently associated with worse overall and recurrence-free survival in nonmetastatic colorectal cancer. For better oncologic outcomes, our findings indicate a need to reduce the use of blood transfusion during the perioperative period.

Prognostic Significance of Lymphovascular Space Invasion in the Absence of Lymph Node Metastases in Early-Stage Endometrial Cancer

2018 ◽  
Vol 28 (5) ◽  
pp. 890-894 ◽  
Author(s):  
Ellen Cusano ◽  
Victoria Myers ◽  
Rajiv Samant ◽  
Talia Sudai ◽  
Allison Keller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factor ◽  
Early Stage ◽  
Prognostic Significance ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Node Negative ◽  
Early Stage Endometrial Cancer ◽  
Lymphovascular Space Invasion

ObjectiveLymphovascular space invasion (LVSI) has been defined as a significant adverse prognostic factor in early-stage endometrial cancer, primarily because of its high association with nodal metastases. This study aimed to determine if LVSI provides any prognostic significance in pathologic node-negative surgically staged (T1N0) endometrial cancer patients.Methods/MaterialsThis retrospective cohort study included all patients with pathologic stage T1N0 endometrial carcinoma treated at The Ottawa Hospital Cancer Centre from 1998 to 2007. Patient demographics, pathologic findings, treatment, and outcome data were collected. Univariate and multivariate cox regression modeling was used to assess significance and adjust for demographic and histopathologic covariates. Kaplan-Meier curves were used to estimate the 5-year overall and recurrence-free survival.ResultsOur study included 400 pathologic stage T1N0 patients who received an initial total hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. The median age at diagnosis was 62 years, and the median follow-up was 66 months. Fifty-four patients (13.5%) had a positive LVSI status, and 346 (86.5%) had a negative LVSI status. The 5-year overall survival was 97.3% in patients without LVSI and 90.9% in those with LVSI (P < 0.001). The 5-year recurrence-free survival was 95.2% in patients without LVSI and 85.9% in those with LVSI (P = 0.006). Univariate analysis identified grade, stage, and LVSI as the covariates significantly associated with time to recurrence, and identified age, grade, stage, and LVSI to be significantly associated with overall survival. There were no significant covariates for recurrence-free survival by multivariate analysis, and only age and LVSI were significant for overall survival.ConclusionsLymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.

scholarly journals Clinical Feature and Prognostic Factors for Repeatedly Recurrent Spinal Chondrosarcoma: A Retrospective Study of 49 Patients in One Single Institution.

2021 ◽  
Author(s):  
Yue Zhang ◽  
Yuduo Xu ◽  
Wenzhi Miao ◽  
Haifeng Wei
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Univariate Analysis ◽  
Surgical Margin ◽  
Clinical Feature ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Favorable Prognostic Factor

Abstract Background: To investigate the clinical feature in prognostic prediction of repeatedly recurrent spinal chondrosarcoma (RRSC). The purpose of this study was to illustrate the clinical parameters of RRSC and to discuss the prognostic factors by statistical analysis.Methods: Univariate and multivariate analyses were performed to investigate independent prognostic factors for recurrence and death of patients with RRSC. Recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier curve, and differences were analyzed by log-rank test. Factors with P < 0.1 extracted by univariate analysis were subjected to multivariate analysis by Cox regression analysis. P < 0.05 were considered statistically significant.Results: Included in this study were 49 patients with RRSC who were followed up by a mean of 31.7 months (median, 25 months; range, 5-93 months). Local recurrence was detected in 33 patients, with death in 28 patients. The final statistical analysis indicated that wide surgical margin (> 4 mm) was the most favorable prognostic factor for both recurrence-free survival (RFS) and overall survival (OS). Meanwhile, fewer number of recurrences (NOR) was in favor of RFS, and lower pathological grade was a significant favorable prognostic factor for OS.Conclusion: Wide surgical margin should be considered in predicting the prognosis of RRSC, including RFS as well as OS. NOR was significant prognostic indicator for RFS, and pathological grading was significantly associated with OS.

scholarly journals Primary tumour ulceration in cutaneous melanoma: its role on TNM stages.

2020 ◽  
Author(s):  
Faruk Tas ◽  
Kayhan Erturk
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Primary Tumour ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Melanoma Patients ◽  
Overall Survival Rates ◽  
Unfavourable Prognostic Factor

Abstract Background Tumour ulceration has unfavourable prognostic factor in stage I–II melanoma. The aim of this study was to question whether tumour ulceration might predict relapse and survival in melanomas of all stages. Methods A total of 911 melanoma patients were analysed. Results The 5-year relapse-free survival rates were 50.0% for ulcerated melanomas and 75.8% for all non-ulcerated melanomas (P = 0.0001). Ulcerated melanomas had lower relapse-free survival rates than non-ulcerated melanomas in all T-stages (P = 0.0001). The relapse-free survival rates were statistically significant for T1 (P = 0.02), T3 (P = 0.01) and T4 (P = 0.004); however, T2 (P = 0.07). There were significant differences between ulcerated melanomas and non-ulcerated melanomas regarding relapse-free survival rates for both N0 (P = 0.0001) and N1 (P = 0.01) patients; poor relapse-free survival rates were found to be in association with ulcerated melanomas (P = 0.06 for N1, P = 0.04 for N2 and P = 0.8 for N3 disease). The 5- year overall survival rates were 55.3 and 81.5% for ulcerated melanomas and non-ulcerated melanomas, respectively (P = 0.0001). Ulcerated melanomas had lower overall survival rates than non-ulcerated melanomas in all T-stages; they were statistically significant for T1 (P = 0.01), T2 (P = 0.03) and T4 (P = 0.006), but not for T3 (P = 0.3). Ulceration predicted poor survival in N0 patients; however, it was not found significant although its overall survival rate was lower in node-positive patients (P = 0.09), and ulceration was a significantly poor prognostic factor only for N3 patients (P = 0.03), but not for N1 (P = 0.9) and N2 patients (P = 0.2). Furthermore, non-metastatic patients with ulcerated melanomas survived significantly less (P = 0.0001), but there were no differences in survivals between ulcerated melanoma and non-ulcerated melanoma metastatic melanoma patients (P = 0.1). Conclusion Primary tumour ulceration has been considered as a poor prognostic factor in local melanomas, but it might also have a potential for predicting survival in loco-regional and advanced melanomas.

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