Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis.
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ABSTRACT:
SUBMITTER: Martin B
PROVIDER: S-EPMC2409786 | biostudies-other | 2004 Dec
REPOSITORIES: biostudies-other
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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: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:BackgroundNeuroendocrine neoplasm (NEN) is a group of rare tumors. Among which, gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common group. The World Health Organization (WHO) classified these tumors into three different grades (G1, G2, and G3) based on Ki-67 and mitotic rate, and updated the classification in 2019. Several previous studies proved that Ki-67 was related to tumor prognosis, but others still reported that Ki-67 had no predictive value for tumor prognosis. There are different conclusions between studies regarding the correlation between Ki-67 and tumor prognosis, and there is a lack of studies about this correlation of GEP-NENs. Further analysis is still needed to evaluate the prognostic value of Ki-67 in GEP-NENs, to provide reference for clinical decisions.MethodsA total of 303 studies were retrieved that included Ki-67, GEP-NENs, prognosis, survival, and other subject terms and keywords. We excluded studies that did not show complete Ki-67 index, number of patients and 5-year survival data available for meta-analysis, non-cohort studies, articles published before 2000 or not published in English. Fifteen studies were finally included to assess the value of Ki-67 in the prognosis of patients with GEP-NENs using a random-effects model.ResultsThe cumulative 5-year survival rate for GEP-NEN G1 (Ki-67 ≤2%), G2 (Ki-67 2-20%) and G3 (Ki-67 >20%) was 86%, 65%, 25% respectively. The 5-year survival rate of GEP-NEN G1 (Ki-67 <3%, first revised in WHO classification 2017, redefined WHO classification 2019) and G1 (Ki-67 ≤2%, WHO classification 2010) was 97% and 84% respectively.ConclusionsThe overall prognosis of GEP-NENs patients showed a decreasing trend with the increase of Ki-67, which confirmed the significance of Ki-67 index as a prognostic marker for the prognosis of GEP-NENs. Increasing the cut-off value of Ki-67 index for G1 grade from ≤2% to <3% according to WHO classification 2019 did not significantly decrease the 5-year survival rate.
| S-EPMC10493787 | biostudies-literature
Project description:BACKGROUND: Homeobox (HOX) genes are expressed in adult cells and regulate expression of genes involved in cell proliferation as well as cell-cell and cell-extracellular matrix interactions. Dysregulation of HOX gene expression plays important roles in carcinogenesis in a variety of organs. Through data mining on a published transcriptome dataset, this study first identified Homeobox protein Hox-C6 (HOXC6) gene as one of the differentially upregulated genes in nasopharyngeal carcinoma (NPC). We aimed to evaluate HOXC6 expression and its prognostic effect in a large cohort of NPC patients. METHODS: We retrospectively examined the HOXC6 expression and Ki-67 index by immunohistochemistry in biopsy specimens from 124 patients with non-metastasized NPC. The results were correlated with the clinicopathological variables including disease-specific survival (DSS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS). RESULTS: HOXC6 high expression was positively correlated with increased Ki-67 labeling index, and significantly associated with increment of tumor stage (p=0.024), advanced nodal status (p<0.001) and American Joint Committee on Cancer (AJCC) stage (p=0.002). Its expression also correlated with worse prognosis in terms of DSS (p=0.008), MeFS (p=0.0047) univariately. In multivariate analyses, HOXC6 expression still remained prognostically independent to portend worse DSS (p=0.015, hazard ratio=1.988) and MeFS (p=0.036, hazard ratio=1.899), together with stage III-IV (p=0.024, DSS; p=0.043, MeFS). CONCLUSION: In summary, our results suggest HOXC6 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients.
| S-EPMC5535720 | biostudies-literature
Project description:BackgroundLung cancer ranks as the leading cause of cancer-related deaths worldwide and we performed this meta-analysis to investigate eligible studies and determine the prognostic effect of Ki-67.MethodsIn total, 108 studies in 95 articles with 14,732 patients were found to be eligible, of which 96 studies reported on overall survival (OS) and 19 studies reported on disease-free survival (DFS) with relation to Ki-67 expression in lung cancer patients.ResultsThe pooled hazard ratio (HR) indicated that a high Ki-67 level could be a valuable prognostic factor for lung cancer (HR?=?1.122 for OS, P?<?0.001 and HR?=?1.894 for DFS, P?<?0.001). Subsequently, the results revealed that a high Ki-67 level was significantly associated with clinical parameters of lung cancer including age (odd ratio, OR?=?1.246 for older patients, P?=?0.018), gender (OR?=?1.874 for males, P?<?0.001) and smoking status (OR?=?3.087 for smokers, P?<?0.001). Additionally, significant positive correlations were found between Ki-67 overexpression and poorer differentiation (OR?=?1.993, P?=?0.003), larger tumor size (OR?=?1.436, P?=?0.003), and higher pathologic stages (OR?=?1.867 for III-IV, P?<?0.001). Furthermore, high expression of Ki-67 was found to be a valuable predictive factor for lymph node metastasis positive (OR?=?1.653, P?<?0.001) and advanced TNM stages (OR?=?1.497 for stage III-IV, P?=?0.024). Finally, no publication bias was detected in any of the analyses.ConclusionsThis study highlights that the high expression of Ki-67 is clinically relevant in terms of the prognostic and clinicopathological characteristics for lung cancer. Nevertheless, more prospective well-designed studies are warranted to validate these findings.
| S-EPMC6088431 | biostudies-literature
Project description:This study aimed to optimize slope and energy levels for evaluating Ki-67 expression in lung cancer using virtual monoenergetic imaging and compare the predictive efficiency of different energy spectrum slopes (λHU) for Ki-67. Forty-three patients with primary lung cancer confirmed via pathological examination were enrolled in this study. They underwent baseline arterial-phase (AP) and venous-phase (VP) energy spectrum computed tomography (CT) scanning before surgery. The CT values were 40-190 keV, with 40-140 keV indicating pulmonary lesions at AP and VP, and P < 0.05 indicating a statistically significant difference. An immunohistochemical examination was conducted, and receiver operating characteristic curves were used to analyze the prediction performance of λHU for Ki-67 expression. SPSS Statistics 22.0 (IBM Corp., NY, USA) was used for statistical analysis, and χ2, t, and Mann-Whitney U tests were used for quantitative and qualitative analyses of data. Significant differences were observed at the corresponding CT values of 40 keV (as 40-keV is considered the best for single-energy image for evaluating Ki-67 expression) and 50 keV in AP and at 40, 60, and 70 keV in VP between high- and low-Ki-67 expression groups (P < 0.05). In addition, the λHU values of three-segment energy spectrum curve in both AP and VP were quite different between two groups (P < 0.05). However, the VP data had greater predictive values for Ki-67. The areas under the curve were 0.859, 0.856, and 0.859, respectively. The 40-keV single-energy sequence was the best single-energy sequence to evaluate the expression of Ki-67 in lung cancer and to obtain λHU values using the energy spectrum curve in the VP. The CT values had better diagnostic efficiency.
| S-EPMC9992396 | biostudies-literature
Project description:BACKGROUND:Ki-67 is a typical immunohistochemical marker for cell proliferation. Higher expression of Ki-67 is correlated with poor clinical outcomes in several cancers. However, the prognostic value of Ki-67 on the prognosis of meningiomas is still controversial. The purpose of this meta-analysis was to evaluate the prognostic value of Ki-67 in meningiomas. METHODS AND MATERIALS:We searched Medline and EMBASE from inception to December 31, 2018, to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) for overall survival (OS) and disease/progression/recurrence-free survival (D/P/RFS) were estimated. RESULTS:A total of 43 studies, comprising 5012 patients, were included in this analysis. Higher Ki-67 expression levels were significantly associated with worse OS (HR = 1.565; 95% CI: 1.217-2.013) and D/P/RFS (HR = 2.644; 95% CI: 2.264-3.087) in meningiomas. Subgroup analysis revealed that all the included factors (ethnicity, tumor grade, HR sources, definition of cutoffs, cutoff values) for heterogeneity investigation can affect the pooled results. Among them, the definitions of cutoffs and cutoff values factor are the two main contributors toward heterogeneity. Multivariable meta-regression analysis also showed that methodologies used for cutoff value definition contributed to the high inner-study heterogeneity. CONCLUSIONS:Higher Ki-67 expression levels negatively influenced survival in meningiomas. A higher cutoff value (>4%) is more appropriate for prognosis prediction. It is highly recommended that Ki-67 expression profile could be assessed in meningiomas treatment for predicting survival. And patients with elevated expression of Ki-67 need to have close follow-ups.
| S-EPMC7478528 | biostudies-literature
Project description:BackgroundRadiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC.MethodsOriginal studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression.ResultsWe identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86-0.92) in the training set, and 0.87 (95% CI: 0.82-0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81-0.90) in the training set, and 0.79 (95% CI: 0.73-0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I 2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased.ConclusionRadiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953.
| S-EPMC10792117 | biostudies-literature
Project description:BackgroundThis meta-analysis aimed to identify the prognostic role of Ki-67 in patients with nasopharyngeal carcinoma (NPC).MethodsRelevant studies were retrieved in the PubMed, Embase, Web of Science, and Cochrane Library databases up to November 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ki-67 expression and survival outcomes. Combined odds ratios (ORs) and 95% CIs were measured as effect size on the association between Ki-67 expression and clinical factors.ResultsA total of eight studies involving 936 patients with NPC were included in this meta-analysis. The pooled HR indicated that Ki-67 expression was significantly associated with poor overall survival (HR = 2.86, 95% CI = 1.91-4.27, p < 0.001), progression-free survival (HR = 1.78, 95% CI = 1.15-2.74, p = 0.009), and distant metastasis-free survival (HR = 1.65, 95% CI = 1.15-2.36, p = 0.007). However, there was no significant correlation between Ki-67 expression and local recurrence-free survival (HR = 1.07, 95% CI = 0.54-2.14, p = 0.843). Ki-67 overexpression was associated with higher T stage (OR = 1.48, 95% CI = 1.00-2.20, p = 0.052), and the relationship between Ki-67 expression and advanced stage was nearly significant (OR = 2.25, 95% CI = 0.99-5.14, p = 0.054). However, high Ki-67 expression was not significantly correlated with sex, age, N stage, or histological type.ConclusionThis meta-analysis demonstrated that Ki-67 overexpression was a significant marker for poor prognosis in patients with NPC. Ki-67 should be recommended as a useful index for prognostication in patients with NPC.
| S-EPMC7509738 | biostudies-literature