Prognostic and clinicopathological value of Ki-67 expression in patients with nasopharyngeal carcinoma: a meta-analysis
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ABSTRACT:
SUBMITTER: Shi Z
PROVIDER: S-EPMC7509738 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundKi-67 is an established marker of cell proliferation, and the Ki-67 index correlates with the clinical course of several cancer types, including bladder cancer (BC). However, the clinicopathological and prognostic significance of Ki-67 in bladder cancer remains unclear. Therefore, we performed a systematic review and meta-analysis to clarify this relationship.MethodsA comprehensive literature search for relevant studies published up to February 1, 2016, was performed using PubMed, Cochrane Library, Embase and ISI Web of Knowledge. The effects of Ki-67 expression on survival outcome in patients with BC and BC subtypes were evaluated. Furthermore, the relationship between Ki-67 expression and the clinicopathological features of BC were assessed.ResultsThirty-one studies with 5147 bladder cancer patients were selected for evaluation. Ki-67 expression was significantly associated with shorter recurrence-free (HR 1.69, 95% CI: 1.33-2.14), progression-free (HR 1.89, 95% CI: 1.43-2.51), overall (HR 2.03, 95% CI: 1.31-3.16), and cancer-specific (HR 1.69, 95% CI: 1.47-1.95) survival. Moreover, whereas high expression was more common in high tumor stage, recurrence status, tumor size, there was no correlation between high Ki-67 expression and age, gender, smoking habits, and tumor number. Importantly, analysis of the different subgroups of BC suggested that significant correlations between high Ki-67 expression and survival outcome (recurrence-free/progression-free/overall/cancer-specific survival) are present only in European-American patients.ConclusionThe present results indicate that over-expression of Ki-67 is distinctly correlated with poor patient survival. Ki-67 may serve as a valuable biomarker for prognosis in BC patients, particularly in non-Asian BC patients. The results suggest no significant association between Ki-67 expression and BC prognosis in Asian patients. Further efforts are needed to fully clarify this relationship.
| S-EPMC4943634 | biostudies-literature
Project description:Previous studies have elevated the prognostic value of Ki-67 in renal cell carcinoma (RCC), but the reports are controversial and inconsistent. We conducted a systematic review and meta-analysis to clarify the significance of Ki-67 in RCC prognosis. We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until April 2016. Based on the inclusion and exclusion criteria, 20 studies, including 5,398 patients, were eligible for further analysis. Results showed that high Ki-67 expression in RCC was associated with poor OS (HR = 1.95, 95% CI: 1.44-2.64), CSS (HR = 1.67, 95% CI: 1.47-1.89), and DFS (HR = 2.56, 95% CI: 1.79-3.67). In addition, high Ki-67 expression was significantly associated with TNM stage (III/IV vs. I/II: RR = 2.03, 95% CI: 1.68-2.44), pathological T stage (T3/T4 vs. T1/T2: RR = 1.67, 95% CI: 1.35-2.06), metastasis (yes vs. no: RR = 2.15, 95% CI: 1.77-2.62), and Fuhrman grade (III/IV vs. I/II: RR = 1.77, 95% CI: 1.20-2.60). Our study suggested that Ki-67 was a prognostic marker in RCC. High Ki-67 expression was correlated with poor prognosis and advanced clinicopathological features, and it could serve as a biomarker for disease management.
| S-EPMC5347162 | biostudies-literature
Project description:The prognostic value and clinicopathologic significance of Ki-67 expression in gastric cancer patients was controversial. This meta-analysis was performed to clarify the prognostic value and clinicopathologic significance of Ki-67 expression in gastric cancer patients.Several electronic databases were searched for eligible studies. The pooled odds ratio (OR), hazard ratios (HR) and 95% confidence interval(CI) were calculated to explore the prognostic value and clinicopathologic significance of Ki-67 expression for disease free survival and overall survival.Totally 5600 gastric cancer patients from 29 studies were included in this study. High Ki-67 expression was significantly related with Lauren's classification (OR = 1.70; P = 0.001; 95%CI: 1.40-2.06) and tumor size(OR = 1.54; P = 0.006; 95%CI: 1.14-2.09). However, high Ki-67 expression was not significantly associated with lymph node metastasis (OR = 1.37; P = 0.138; 95% CI: 0.90-2.08) , tumor stage (OR = 1.31; P = 0.296; 95% CI: 0.79-2.16) and tumor differentiation (OR = 1.03; P = 0.839; 95% CI: 0.78-1.35). The pooled HRs were 1.87(P = 0.001; 95% CI 1.30-2.69) for disease free survival and 1.23(P = 0.005; 95% CI 1.06-1.42) for overall survival.High Ki-67 expression may serve as a predictive biomarker for poor prognosis in gastric cancer patients. Stratification by Ki-67 expression may be a consideration for selection of therapeutic regimen and integrated managements.
| S-EPMC5564848 | biostudies-other
Project description:In this study, we evaluated SOX2, Cyclin D1, p53, and ki-67 expression immunohistochemically in 117 samples of surgically resected esophageal squamous cell carcinoma (ESCC) and matched normal tumor adjacent tissues and correlated the expression with clinicopathological finding and patient survival. Lymph node metastasis was observed in 36.8% of patients, and organ metastasis was observed in 17.9%. We detected high expression of SOX2, Cyclin D1, p53, and ki-67 in 46.1%, 70.1%, 54.7%, and 32.5% of ESCC tissues, respectively. SOX2 is localized in the tumor cell nuclei, and its expression was significantly associated with N stage (p=0.034) and differentiation (p=0.003) and ki-67 expression (p=0.001), whereas increased Cyclin D1 expression was correlated with high p53 (p=0.015). With regard to survival, we found that ESCC patients with high SOX2 expression had significantly better survival time than those with low SOX2 expression (p=0.021). A multivariate Cox analysis revealed that therapy and high p53 expression and venous invasion were independent predictors of unfavorable prognosis in overall survival (p=0.039, p=0.004, and p=0.023, respectively). Furthermore, higher T stage, clinical stage (pTNM), venous invasion, and high p53 expression were independent predictors of a worse progression-free survival. Notably, co-overexpression of p53 and Cyclin D1 was significantly correlated with poor overall survival and progression-free survival (p=0.029 and p=0.0227, respectively). Therefore, SOX2 might be considered as a potential prognostic indicator and a potential target for therapeutic targets in ESCC. p53 staining and combined p53 and Cyclin D1 expression had significantly unfavorable prognostic value for patients with ESCC. These findings provide more insight into ESCC; thus, further investigations into molecular mechanisms of drug resistance are essential.
| S-EPMC6114475 | biostudies-literature
Project description:INTRODUCTION:The objective of this study was to examine the prognostic value of Ki-67 expression in conversion therapy for colorectal liver-confined metastases. METHODS:We enrolled a total of 96 patients including 54 patients who received oxaliplatin- or irinotecan-based chemotherapy and curative hepatectomy for initially unresectable metastases (conversion group) and 42 patients with initially resectable liver metastases (straight hepatectomy group). Ki-67 expression was examined in 96 resected specimens but excluded the 2 specimens that revealed no residual cancer cells in conversion group. RESULTS:Conversion therapy leads to greater survival that is equivalent to that straight hepatectomy group. In conversion group, high Ki-67 expression (> 30%) levels were detectable in 33 patients (64%) after chemotherapy prior to conversion therapy. High Ki-67 expression was significantly associated with shorter disease-free survival and worse overall survival (P < 0.01 in both), and was an independent worse prognostic factor of disease-free survival and overall survival (hazard ratio [HR] and P-values were 5.608, 0.001 and 5.366, 0.04, respectively) in patients with conversion therapy. Interestingly, even in the patients with RECIST PR (n = 32), high Ki-67 expression was significantly shorter disease-free survival compared to low Ki-67 expression (P < 0.001). In contrast to conversion group, there was no significant difference in disease free survival and overall survival between low (n = 14, 33%) and high (n = 28, 67%) Ki-67 expressions in patients with straight hepatectomy (P = 0.14 and 0.74, respectively). CONCLUSIONS:Residual Ki-67 expression is a useful biomarker for worse prognostic outcomes after conversion therapy. High Ki-67 expression may be a biomarker of micrometastases containing aggressive cancer cells.
| S-EPMC4449450 | biostudies-literature
Project description:The abnormal expression of Beclin-1 has recently been investigated in a variety of tumors. However, previous studies have obtained contradicting results regarding the clinical and prognostic value of Beclin-1 in hepatocellular carcinoma (HCC). We performed a meta-analysis to clarify the prognostic value of Beclin-1 and its correlations with clinical pathological parameters in HCC.Relevant studies were systematically retrieved from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Wan Fang and Chinese VIP databases. We used the Newcastle-Ottawa scale (NOS) to estimate the quality of the involved studies.Ten eligible studies with 1086 HCC patients were included in this study. Our results showed that decreased Beclin-1 expression in HCC related to histological grade [poor-undifferentiated vs. well-moderate: odds ratio (OR)?=?2.34, 95% confidence interval (CI)?=?1.65-3.32, P?<?0.00001]. The pooled hazard ratio (HR) (HR?=?1.43, 95% CI?=?1.17-1.75, P?=?0.0004) indicated that decreased Beclin-1 expression correlated with poor overall survival (OS).This meta-analysis indicated that decreased Beclin-1 expression might relate to poor differentiation and unfavorable outcome in HCC.
| S-EPMC6092876 | biostudies-other
Project description:BackgroundThe prognostic value of p53 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic and clinicopathological significance of p53 protein expression in RCC.Materials and methodsLiterature was identified from PubMed, Embase, Web of Science, and Cochrane database, which investigated the relationships between p53 expression and outcomes. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with p53 were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test.ResultsA total of 2,013 patients from 22 studies were included in the meta-analysis. The results showed that p53 positive expression is associated with poor overall survival (OS) (HR = 2.17, 95% confidence [CI]: 1.51-3.13) and cancer-specific survival (CSS) (HR = 1.59, 95% CI: 1.19-2.12) in RCC. In addition, p53 positive expression was closely correlated with TNM stage (III/IV vs. I/II: OR = 2.51, 95% CI: 1.05-6.00), Fuhrman grade (III/IV vs. I/II: OR = 1.80, 95% CI: 1.24-2.63), and distant metastasis (M1 vs. M0: OR = 1.70, 95% CI: 1.16-2.49), but not related to lymph node involvement (N1 vs. N0: OR = 1.32, 95% CI: 0.80-2.18), primary tumor stage (pT3/pT4 vs. pT1/pT2: OR = 1.16, 95% CI: 0.88-1.53), and sex (n = 2, male vs. female, OR = 1.09, 95% CI: 0.70-1.68).ConclusionsThis study suggests that p53 positive expression is correlated with poor prognosis and advanced clinicopathological features in patients with RCC, which indicates that p53 is a potentially effective therapeutic target.
| S-EPMC5731961 | biostudies-literature
Project description:Ki-67 serves as a prominent cancer marker. We describe how expression of the MKI67 gene coding for Ki-67 is controlled during the cell cycle. MKI67 mRNA and Ki-67 protein are maximally expressed in G2 phase and mitosis. Expression is dependent on two CHR elements and one CDE site in the MKI67 promoter. DREAM transcriptional repressor complexes bind to both CHR sites and downregulate the expression in G0/G1 cells. Upregulation of MKI67 transcription coincides with binding of B-MYB-MuvB and FOXM1-MuvB complexes from S phase into G2/M. Importantly, binding of B-MYB to the two CHR elements correlates with loss of CHR-dependent MKI67 promoter activation in B-MYB-knockdown experiments. In knockout cell models, we find that DREAM/MuvB-dependent transcriptional control cooperates with the RB Retinoblastoma tumor suppressor. Furthermore, the p53 tumor suppressor indirectly downregulates transcription of the MKI67 gene. This repression by p53 requires p21/CDKN1A. These results are consistent with a model in which DREAM, B-MYB-MuvB, and FOXM1-MuvB together with RB cooperate in cell cycle-dependent transcription and in transcriptional repression following p53 activation. In conclusion, we present mechanisms how MKI67 gene expression followed by Ki-67 protein synthesis is controlled during the cell cycle and upon induction of DNA damage, as well as upon p53 activation.
| S-EPMC8629999 | biostudies-literature
Project description:Background: The prognostic value of programmed cell death ligand-1 (PD-L1) in patients with nasopharyngeal carcinoma (NPC) remains controversial. Therefore, we conducted this meta-analysis to understand the role of PD-L1 in NPC. Method: We searched PubMed, Embase, Web of Science, and Cochrane Library up to April 2019. We determined the pooled hazard ratio (HR) and 95% confidence intervals (CIs) to assess the relationship between PD-L1 and various survival outcomes. Begg's funnel plot was used to assess any publication bias. Results: Eleven studies involving 1,315 patients were included in this meta-analysis. For overall survival (OS), the HR was 1.48 and 95% CI was 1.00-2.18 (p = 0.049). For disease-free survival (DFS), the HR was 1.51 and 95% CI was 0.85-2.69 (p = 0.162). For distant metastasis-free survival (DMFS), the HR was 1.75 and 95% CI was 0.64-4.79 (p = 0.277). For local recurrence-free survival (LRFS), the HR was 0.67 and 95% CI was 0.06-8.16 (p = 0.756). The results of prognosis of PD-L1 and OS were more significant after sensitivity analysis. The pooled odds ratio indicated that PD-L1 expression was not associated with T stage, N stage, M stage, overall stage, sex, age, smoking, or alcohol intake. No publication bias was found. Conclusion: Our meta-analysis showed that PD-L1 overexpression in NPC was associated with a poor OS and may be useful as a novel prognostic factor for NPC.
| S-EPMC6823255 | biostudies-literature
Project description:IntroductionKi-67 expression is a biomarker for proliferation. Its prognostic value is recognized in breast cancer (BC) patients with negative axillary nodes, but is less clear in BC patients with positive axillary lymph nodes.MethodsWe retrospectively reviewed the medical records of 1131 Chinese BC patients treated from January 2002 to June 2007 and 450 patients met the inclusion criteria: positive nodes, adjuvant therapy, and complete biomarker profile (estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki-67). Univariate and multivariate regression analysis were used to correlate biomarkers and tumor characteristics with metastasis free survival (MFS) and overall survival (OS).ResultsMedian follow-up time was 46 months (range 5-76 months). The Ki-67 expression was associated significantly with histological grade, ER, PR, HER2, and P53 status (P<0.05). Tumor stage, nodal stage, and ER status were independent prognostic factors for MFS. Ki-67 status was associated significantly with OS but not MFS. To determine whether the extent of LN involvement in the BC patients influenced the role of Ki-67 in survival rates, we compared these variables in patients with 1-3 positive lymph nodes (N1) to those of patients with ≥ 4 positive lymph nodes. Ki-67 status was an independent prognostic factor for MFS (Hazard Ratio, 3.27, P = 0.026) and overall survival (HR, 10.64, P = 0.007) in patients with 1-3 positive nodes (N1).ConclusionsThe possibility that Ki-67 expression together with clinical factors can improve prediction of the prognosis of BC patients with 1 ∼ 3 positive axillary lymph nodes warrants further studies.
| S-EPMC3911937 | biostudies-literature