The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

Pascale, Mariarosa; Aversa, Cinzia; Barbazza, Renzo; Marongiu, Barbara; Siracusano, Salvatore; Stoffel, Flavio; Sulfaro, Sandro; Ricevuto, Enrico; Bonin, Serena; Stanta, Giorgio

doi:10.1515/raon-2016-0033

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…It is well known that Ki67 is a biomarker of cellular proliferation in tumors, and is associated with poor prognosis [34, 35]. In T lymphocytes, Ki67 expression is also a good indicator of T cell activation and reinvigoration [16].…”

Section: Discussionmentioning

confidence: 99%

Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma

Niu

Yin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, and is the most common type of lymphoma in adults. Although significant progress in treatment has been made using chemotherapy combinations, there exist a large amount of relapse or refractory cases. Thus, effective clinical biomarkers for DLBCL are urgently needed. Our study aims to explore the predictive significance of using the immune response to tumor burden ratio [defined as the lymphocyte to monocyte ratio (LMR)/lactate dehydrogenase (LDH) levels] in 184 DLBCL patients and the potential mechanism underlying the use of the LMR to tumor burden ratio in predicting patient survival. Methods: The correlation between serum LDH levels and tumor levels assessed by PET-CT was determined using Spearman’s correlation analysis. Clinical data from 184 DLBCL patients was assessed using receiver operating characteristic curve analysis and survival analysis. The potential correlation between tumor burden and lymphocytes or monocytes was analyzed by immunohistochemical staining, flow cytometry, and ELISA analysis of patient samples. In addition, we performed in vitro studies to further determine the effects of tumor burden on the anti-tumor activity of T lymphocytes. Results: We observed that serum LDH was an excellent surrogate marker of tumor burden in DLBCL patients, and that the ratio of LMR to LDH was an independent prognostic biomarker capable of predicting survival in DLBCL patients. Further analysis showed that a high tumor burden was correlated with decreased Ki67 expression in T cells, either in the solid tumor tissue or in the circulating blood. In addition, based on an in vitro co-culture study, a higher tumor burden led to the suppression of the anti-tumor response of T cells. Furthermore, we found that a higher tumor burden was correlated with the differentiation of monocytes to tumor associated macrophages in the tumor micro-environment. Both results demonstrate the importance of considering both the immune system and tumor burden for prognostic analysis. Conclusion: Our study has identified a novel clinical biomarker, namely, the immune response to tumor burden ratio, that can be used to distinguish survival outcomes in DLBCL patients, and demonstrated the potential mechanism underlying the use of this biomarker, that incorporates both the immune system and tumor burden, for use in future clinical applications.

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Section: Discussionmentioning

confidence: 99%

Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma

Niu

Yin

et al. 2018

Cell Physiol Biochem

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“…The marker of proliferation, Ki-67 (MKI67), functions to mark tumor cell proliferation, including in the prostate, and has a close relation to the epithelial-mesenchymal transition (EMT) (Lindsay et al, 2016). Ki67 may improve the prediction of prostate cancer outcomes based on pathological standard parameters, improving prognosis as well as the monitoring of prostate cancer patients (Pascale et al, 2016). TOP2A is considered to be a biomarker for early identification of patients who have increased metastatic potential (Labbé et al, 2017).…”

Section: Selection Real Core Genesmentioning

confidence: 99%

Identification of core genes associated with prostate cancer progression and outcome via bioinformatics analysis in multiple databases

Wang

Yan

et al. 2020

PeerJ

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The morbidity and mortality of prostate carcinoma has increased in recent years and has become the second most common ale malignant carcinoma worldwide. The interaction mechanisms between different genes and signaling pathways, however, are still unclear. Methods Variation analysis of GSE38241, GSE69223, GSE46602 and GSE104749 were realized by GEO2R in Gene Expression Omnibus database. Function enrichment was analyzed by DAVID.6.8. Furthermore, the PPI network and the significant module were analyzed by Cytoscape, STRING and MCODE.GO. Pathway analysis showed that the 20 candidate genes were closely related to mitosis, cell division, cell cycle phases and the p53 signaling pathway. A total of six independent prognostic factors were identified in GSE21032 and TCGA PRAD. Oncomine database and The Human Protein Atlas were applied to explicit that six core genes were over expression in prostate cancer compared to normal prostate tissue in the process of transcriptional and translational. Finally, gene set enrichment were performed to identified the related pathway of core genes involved in prostate cancer. Result Hierarchical clustering analysis revealed that these 20 core genes were mostly related to carcinogenesis and development. CKS2, TK1, MKI67, TOP2A, CCNB1 and RRM2 directly related to the recurrence and prognosis of prostate cancer. This result was verified by TCGA database and GSE21032. Conclusion These core genes play a crucial role in tumor carcinogenesis, development, recurrence, metastasis and progression. Identifying these genes could help us to understand the molecular mechanisms and provide potential biomarkers for the diagnosis and treatment of prostate cancer.

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“…Moreover, our results also showed a positive correlation between plasma C-MYC level and Ki67 index. It has been reported that the protein Ki67 is expressed in the nucleus of cycling cells and used to measure the activity of cell proliferation [47][48][49]. Ki67 index is recognized as an independent prognostic factor in breast cancer [50][51][52][53][54], high Ki67 index is associated with a poor prognosis in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Plasma C-MYC Level Manifesting As An Indicator in Progression of Breast Cancer

Shi

Huang

et al. 2019

Biomark. Med.

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Aim: To investigate whether plasma C-MYC level could be an indicator in clinical progression of breast cancer. Materials & methods: Plasma level of C-MYC expression was detected by quantitative real time PCR and the level of c-myc protein in breast cancer tissues was detected by immunohistochemistry. The expression level of C-MYC mRNA in supernatant of cancer cells culture was measured compared with the nonbreast cancer cells. Results: Plasma C-MYC level was significantly higher in patients with breast cancer than that in the controls, which associated with clinical stages, lymph node status, etc. Receiver operating characteristic curve analysis showed the sensitivity and specificity of plasma C-MYC level for diagnosis of breast cancer were 63.6 and 81.8%, respectively. The expression of c-myc protein in breast cancer tissues was associated with plasma C-MYC level, even C-MYC level in supernatant of cancer cells was elevated. Conclusion: Plasma C-MYC level might be a potential indicator in progression of breast cancer.

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The proliferation marker Ki67, but not neuroendocrine expression, is an independent factor in the prediction of prognosis of primary prostate cancer patients

Cited by 30 publications

References 41 publications

Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma

Ratio of Immune Response to Tumor Burden Predicts Survival Via Regulating Functions of Lymphocytes and Monocytes in Diffuse Large B-Cell Lymphoma

Identification of core genes associated with prostate cancer progression and outcome via bioinformatics analysis in multiple databases

Plasma C-MYC Level Manifesting As An Indicator in Progression of Breast Cancer

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