Kallikrein gene family as biomarkers for recurrent prostate cancer

Boyukozer, Fatma Busra; Tanoğlu, Esra Güzel; Özen, Mustafa; Ittmann, Michael; Aslan, Elif Sibel

doi:10.3325/cmj.2020.61.450

Cited by 9 publications

(7 citation statements)

References 21 publications

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“…In addition, KLK9 expression is low in all three cell lines. The role of KLK9 in prostate cancer is still unclear; it has only been shown that KLK9 expression was increased in recurrent tissue of prostate cancer patients (7). It is possible that KLK9 expression might be considered as a biomarker for analyzing tissues after treatment, but not suitable for early detection.…”

Section: Discussionmentioning

confidence: 99%

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines

Huang

Chen

et al. 2023

In Vivo

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Background/Aim: Surface biomarkers, such as CD44 and CD133, have been demonstrated to be expressed in prostate cancer cells, and our previous study has shown that prostate cancer cell lines could be divided into three groups according to the single and combined expression pattern of CD44 and 133. In order to refine prognostication in prostate cancer cells, we further investigated genetic biomarkers, prostate cancer antigen 3 (PCA3), kallikrein 4 (KLK4), and KLK9 in different prostate cancer cell lines. Materials and Methods: CWR22Rv1, PC3, and DU145 cell lines were cultured until 95% confluence. The single expression of CD44 or CD133 and their combined expression were analyzed by flow cytometry, and gene expression of b-actin, PCA3, KLK4, and KLK9 was analyzed by real-time polymerase chain reaction. Results: The single expression of CD133 was less than 4% in all cell lines examined. PC3 and DU145 cells displayed a high expression of CD44 (>91%), whereas CWR22Rv1 was the only cell line that demonstrated a high co-expression of both CD44 and CD133 (>91%). In addition, PC3 and DU145 displayed low expression of PCA3, KLK4, and KLK9 when compared with their own b-actin expression. In contrast, CWR22Rva showed high expression of PCA3 and KLK4 although KLK9 expression was also low. Conclusion: Both surface and genetic biomarkers should be validated for a more accurate prognosis in prostate cancer.Prostate cancer is one of the most common cancers in men. Even during the COVID-19 pandemic, prostate cancer was still more widespread among deaths (1). Indeed, it has been shown that prostate cancer patients had higher susceptibility to COVID-19 infection, leading to higher mortality and hospitalization rates than other solid tumor patients (2). Therefore, the more accurate detecting methods have been critical for early cancer detection and tumor progression monitoring. Screening biomarkers has become a critical method for prostate cancer diagnosis and monitoring in order to achieve more accurate treatment (3).Prostate cancer cell lines have been useful tools to investigate whether certain biomarkers can be applied for detecting prostate cancer. We have previously demonstrated that the expression levels of biomarkers, such as CD44 and CD133, were distinct among different prostate cancer cell lines: DU145 and PC3 were CD44 high CD133 low , CWR22Rv1 was (CD44 + CD133 + ) high , and LNCaP displayed CD44 low CD133 low characteristics (4). Therefore, not only the single and co-expression of CD44 and CD133 should be investigated when using prostate cancer cell lines, but other biomarkers should also be taken into account. In addition to surface biomarkers, the expression of some genes has been shown to be prostate cancer specific.Prostate cancer antigen 3 (PCA3) is expressed exclusively in the prostate and is over-expressed in prostate cancer tissues (5,6). Kallikrein (KLK) gene family includes 15 serin proteases, and comprises the largest protease family in the human genome (7). Each KLK gene plays a role in prostate cancer, but ov...

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Section: Discussionmentioning

confidence: 99%

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines

Huang

Chen

et al. 2023

In Vivo

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“…Compared to the other luminal subgroups, these cells highly express KLK4, which has been characterized as a potential biomarker for prostate, breast, and ovarian cancers. 58–60 The regulation of KLK4 by androgens 61 and its function as a proliferative factor in the development of prostate cancer 62 suggest a possible role for this KLK4-high luminal subgroup in the promotion of prostatic enlargement. In addition, gene ontology analysis revealed a significant enrichment of established ribosomal gene sets in these KLK4-high cells.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptional profiling of benign prostatic hyperplasia reveals a progenitor-like luminal epithelial cell state within an inflammatory microenvironment

Unno,

Akutagawa,

Song

et al. 2023

Preprint

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Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Here, we characterize at single cell resolution the cellular states of BPH and identify cell populations enriched in BPH that contribute to cell proliferation and inflammation. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single cell RNA-seq data was performed to annotate all cell types. Pseudotime, gene set enrichment, gene ontology, and ligand-receptor analyses were performed. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup was more closely related to club and basal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Unique interactions highlighting MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammation in the prostate, were found between fibroblasts and the progenitor luminal subgroup. This luminal subgroup also interacted with neutrophils and macrophages through MIF. Our single-cell profiling of BPH provides a roadmap for inflammation-linked cell subgroups and highlights a novel luminal progenitor subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.

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“…Cognizant of the usually long course of PCa, and the increasing prevalence of metastatic disease, as well as the high risk of local recurrence or progression to metastatic disease, and eventually death, despite initial definitive local treatment [ 1 , 2 , 3 ], it is of translational relevance that we found that a high PSA/AIM expression ratio is associated with enhanced metastability, and disease recurrence in patients with PCa, whereas, a high AIM/PSA ratio is associated with strong castration-induced regression ( Figure 3 and Figure 4 ). Concordant with these findings, in a recent study that prospectively evaluated six candidate biomarkers for detection of pelvic lymph node (LN) metastases (pN1) and prediction of BRFS in treated patients, while KLK2 and KLK3 outperformed the other predictive variables, and correctly classified all pN1 cases as molecular node-positive, KLK3 exhibited the highest concordance (96%) with histopathology for detection of LN metastases in the patients with PCa [ 22 , 23 ], and KLK3 protein expression was significantly enhanced in recurrent PCa tissues compared to the ‘normal’ tissues [ 24 ]. Moreover, Sugisawa et al [ 25 ] attributed the elimination of HCC cells to the AIM/CD5L produced by liver stellate macrophages/Kupffer cells.…”

Section: Discussionmentioning

confidence: 99%

Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer

et al. 2021

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Background: Despite its widespread use, the use of prostate-specific antigen (PSA) alone as a screening biomarker for prostate cancer (PCa) leads often to unwarranted prostate biopsy, over-diagnosis, and consequently, over-treatment, because of its limited specificity. There are reports that the apoptosis inhibitor of macrophage (AIM), secreted mainly by macrophages and epithelial cells, is upregulated during inflammation and facilitates immune recognition of cancerous cells by blocking human regulator of complement activation. Objective: These controversies around the PSA utility necessitate a reexamination of its use as a screening tool. More so, despite the suggested implication of AIM in anticancer immunosurveillance, there is a dearth of information on its role in therapy response, disease progression, and clinical outcomes of patients with PCa. These inform the present study to probe the nature and role of AIM/PSA signaling in anticancer immunity and prognosis in PCa. Methods: A combination of bioinformatics-aided statistical analyses, gene function annotation, and immune infiltrate analyses, coupled with tissue staining, and function assays, namely migration, invasion, and clonogenicity assays, we employed. Results: We demonstrated that AIM and PSA expression levels are inversely correlated in PCa clinical samples and cell lines, with AIMlowPSAhigh defining PCa, compared to AIMhighPSAlow in normal samples. Concomitant aberrant PSA and significantly suppressed AIM expression levels positively correlated with high-grade disease and characterized by advanced stage prostate cancer, regardless of mutation status. We found that a high PSA/AIM ratio is associated with disease recurrence in patients with prostate cancer but is equivocal for overall survival. In addition, PSA-associated AIM suppression is implicated in the enhanced ‘metastability’ of PCa and a high AIM/PSA ratio is associated with strong castration-induced regression. CRISPR-mediated AIM knockout was associated with higher PSA expression while ectopic expression of AIM significantly attenuated the migration and invasive capability of PC3 and DU145 cells. Interestingly, compared to normal samples, we observed that AIM, biomarkers of T-cell activation and M1 phenotype markers are co-suppressed in PCa samples. Conclusion: Herein, we demonstrate that AIM/CD5L binds to PSA and that a high PSA/AIM ratio defines advanced stage PCa (regardless of mutation status), is implicated in enhanced metastability, and associated with disease recurrence, while a high AIM/PSA ratio is associated with strong castration-induced regression. More so, the ectopic expression of AIM significantly enhances the anticancer effect of Pembrolizumab and elicits an increased CD8+ T-cell count in AIMhiPSAloPDL1+ PCa cases that are respondent to Pembrolizumab treatment.

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Kallikrein gene family as biomarkers for recurrent prostate cancer

Cited by 9 publications

References 21 publications

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines

Distinct Expression of Surface and Genetic Biomarkers in Prostate Cancer Cell Lines

Single cell transcriptional profiling of benign prostatic hyperplasia reveals a progenitor-like luminal epithelial cell state within an inflammatory microenvironment

Concomitant High Apoptosis Inhibitor of Macrophage (AIM) and Low Prostate-Specific Antigen (PSA) Indicates Activated T Cell-Mediated Anticancer Immunity, Enhance Sensitivity to Pembrolizumab, and Elicit Good Prognosis in Prostate Cancer

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