• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3929-3937
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• 2016

Gastric cancer (GC) is a major health problem worldwide and is one of the ten most commonly diagnosed cancers in Jordan. GC is usually diagnosed at late aggressive stages in which treatment options are limited. Recently, heat shock proteins (HSPs) were found to be overexpressed in a wide range of malignancies have been considered as promising candidate biomarkers for GC. The aim of this study was to investigate pathogenic roles of a panel of cytosolic HSPs including HSP90, HSP70, HSP60 and HSP27 in GC. Immunohistochemistry was used to assess the level of expression of these proteins in archived tumor samples (N=87) representing various pathological characteristics of GC. HSP90, HSP60 and HSP27 were expressed abundantly in gastric tumors. On the other hand, HSP70 was reduced significantly and also found to be associated with Helicobacter pylori infection in tissues collected from GC patients. Furthermore, HSP27 was found to be associated with the level of differentiation. Our findings indicate a role of HSP70 as a potential prognostic biomarker, patients harboring positive HSP70 expression displaying worse disease free survival than those with negative HSP70 expression. Differential expression of HSPs may play crucial roles in the initiation and progression of GC, and could be exploited as future therapeutic targets.

• Biomedical Science Letters
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• v.24 no.1
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• pp.9-14
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• 2018

Ki-67 has been widely performed and become an important biomarker in worldwide clinics, but the standard cut off value of Ki-67 index in breast cancer is still controversy. The objective study was to understand the Ki-67 in breast cancer subtypes and to investigate relative risk of breast cancer subtypes according to Ki-67 cut off value in Korean breast cancer. Immunohistochemical staining (IHC) for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 index was examined from 123 breast cancer patients. Ki-67 index was significantly overexpressed in PR, ER, and HER2 hormone negative groups. Ki-67 index in Triple negative and HER2 subtypes was shown significantly higher than that in Luminal A and Luminal B subtype. Then, we compared the relative risk of each subtype according to 14% and 20% Ki-67 cut off value, which were applied in most clinics. Especially, 20% Ki-67 cut off value in HER2 and Triple negative subtypes was shown 8.41 fold and 2.83 fold higher relative risk than this in Luminal A subtype. Moreover, Ki-67 index in HER2 2+ or 3+ status showed significantly overexpressed than this in HER2 1+ status. At the 20% Ki-67 cut off value, HER2 1+ or 2+ status and 3+ status showed significant difference. Therefore, the 20% Ki-67 cut off value will be useful as a precise prognostic management and helpful for interpreting diverse outcomes of other subtypes in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1093-1096
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• 2016

The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H & E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5059-5062
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• 2015

Background: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. Aim and objectives: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. Materials and Methods: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione-s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. Results: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Conclusions: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.1
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• pp.291-297
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• 2015

The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3' UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3' UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT-PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3' UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10831-10836
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• 2015

This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5073-5076
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• 2013

Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathological factors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patients who underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198 expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factor and its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher in patients with poor prognosis than those with good prognosis (P<0.05). Kaplan-Meier analysis results showed that the miR-198 expression level had a significant correlation with survival time (P=0.030) and that patients with a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed that patient prognosis (P=0.014), tumor length (P=0.040) and expression (P=0.012), and survival time had a significant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker for selection of cases requiring especial attention.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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• pp.318-325
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• 2021

Background: The diagnosis and prediction of prognosis are important in patients with sepsis, and presepsin is helpful. In this study, we aimed to examine the usefulness of presepsin in predicting the prognosis of sepsis in Korea. Methods: Patients diagnosed with sepsis according to the sepsis-3 criteria were recruited into the study and classified into surviving and non-surviving groups based on in-hospital mortality. A total of 153 patients (32 and 121 patients with sepsis and septic shock, respectively) were included from July 2019 to August 2020. Results: Among the 153 patients with sepsis, 91 and 62 were in the survivor and non-survivor groups, respectively. Presepsin (p=0.004) and lactate (p=0.003) levels and the sequential organ failure assessment (SOFA) score (p<0.001) were higher in the non-survivor group. Receiver operating characteristic curve analysis revealed poor performances of presepsin and lactate in predicting the prognosis of sepsis (presepsin: area under the curve [AUC]=0.656, p=0.001; lactate: AUC=0.646, p=0.003). The SOFA score showed the best performance, with the highest AUC value (AUC=0.751, p<0.001). The prognostic cutoff point for presepsin was 1,176 pg/mL. Presepsin levels higher than 1,176 pg/mL (odds ratio [OR], 3.352; p<0.001), higher lactate levels (OR, 1.203; p=0.003), and higher SOFA score (OR, 1.249; p<0.001) were risk factors for in-hospital mortality. Conclusion: Presepsin levels were higher in non-survivors than in survivors. Thus, presepsin may be a valuable biomarker in predicting the prognosis of sepsis.

• Journal of Periodontal and Implant Science
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• v.51 no.6
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• pp.386-397
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• 2021

Purpose: MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators that modulate gene expression and have been identified as biomarkers for several diseases, including cancer. This study aimed to systematically review the relationship between miRNAs and periodontal disease in humans, and to evaluate the potential of miRNAs as diagnostic and prognostic biomarkers of disease. Methods: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (reference number CRD42020180683). The MEDLINE, Scopus, Cochrane Library, Embase, Web of Science, and SciELO databases were searched for clinical studies conducted in humans investigating periodontal diseases and miRNAs. Expression levels of miRNAs across the different groups were analysed using the collected data. Results: A total of 1,299 references were identified in the initial literature search, and 23 articles were finally included in the review. The study designs were heterogeneous, which prevented a meta-analysis of the data. Most of the studies compared miRNA expression levels between patients with periodontitis and healthy controls. The most widely researched miRNA in periodontal diseases was miR-146a. Most studies reported higher expression levels of miR-146a in patients with periodontitis than in healthy controls. In addition, many studies also focused on identifying target genes of the differentially expressed miRNAs that were significantly related to periodontal inflammation. Conclusions: The results of the studies that we analysed are promising, but diagnostic tests are needed to confirm the use of miRNAs as biomarkers to monitor and aid in the early diagnosis of periodontitis in clinical practice.

• Journal of Gastric Cancer
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• v.19 no.2
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• pp.183-192
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• 2019

Purpose: Due to adverse events, dose reduction or withdrawal of adjuvant chemotherapy is required for some patients. To identify the predictive factors for tolerability to postoperative adjuvant S-1 monotherapy in gastric cancer (GC) patients, we evaluated the predictive values of blood indicators. Materials and Methods: We analyzed 98 patients with pStage II/III GC who underwent postoperative adjuvant S-1 monotherapy. We retrospectively analyzed correlations between 14 parameters obtained from perioperative routine blood tests to assess their influence on the withdrawal of postoperative adjuvant S-1 monotherapy, within 6 months after discontinuation. Results: Postoperative adjuvant chemotherapy was discontinued in 21 patients (21.4%) within 6 months. Univariable analysis revealed that high preoperative albumin-bilirubin (ALBI) scores had the highest odds ratio (OR) for predicting the failure of adjuvant S-1 chemotherapy (OR, 6.47; 95% confidence interval [CI], 2.08-20.1; cutoff value, -2.696). The high ALBI group had a significantly shorter time to failure of postoperative adjuvant S-1monotherapy (hazard ratio, 3.48; 95% CI, 1.69-7.25; P=0.001). Multivariable analysis identified high preoperative ALBI score as an independent prognostic factor for tolerability (OR, 10.3; 95% CI, 2.33-45.8; P=0.002). Conclusions: Preoperative ALBI shows promise as an indicator associated with the tolerability of adjuvant S-1 monotherapy in patients with pStage II/III GC.