International Journal of Biological Markers最新文献

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors.

Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled.

Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy (P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975.

Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer.

Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays.

Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048).

Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Background: The Glasgow Prognostic Score and circulating cytokine levels are related to the prognosis of colorectal cancer and the severity of chronic inflammation. The association between the Glasgow Prognostic Score and circulating cytokines in colorectal cancer remains unclear.

Methods: The levels of 10 circulating cytokines (TNF-α, TGF-β, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) were measured in 128 patients with colorectal cancer. The relationship between the Glasgow Prognostic Score, clinicopathologic variables, and cytokine levels was assessed by univariate and multivariate logistic regression analyses. The correlation among cytokines was also examined.

Results: Patients with advanced stage colorectal cancer had lower levels of albumin (P = 0.003), higher levels of C-reactive protein (CRP; P < 0.001), carcinoembryonic antigen (CEA; P < 0.001), interferon (IFN)-γ (P < 0.001), and interleukin (IL)-10 (P = 0.006), and shorter survival outcomes (P < 0.001). Patients with a high Glasgow Prognostic Score (1 or 2) had lower 5-year progression-free survival and poor overall survival (log-rank P < 0.001). A high Glasgow Prognostic Score was significantly correlated with abnormal CEA levels (CEA > 5 ng/mL, P = 0.033), and higher levels of tumor necrosis factor (TNF)-α (TNF-α ⩾ 53.9 pg/mL, P = 0.035) and IL-10 (IL-10 ⩾ 75.95 pg/mL, P = 0.008). TNF-α, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-13, and IL-23 were significantly correlated with each other (all P < 0.05). Only IL-10 was correlated with abnormal CEA levels (P < 0.001).

Conclusion: The Glasgow Prognostic Score and level of circulating cytokines have an intergroup correlation, and there is a close association among cytokines in colorectal cancer.

Introduction: Prostate cancer has a high incidence in men and is the second cause of cancer death among americans male. microRNA (miR) is becoming a potential new prognostic factor for prostate cancer. Single nucleotide polymorphisms (SNPs) are common polymorphisms, characterized by a single exchange of nitrogen based in the DNA. This polymorphism is present in the miRs, altering their function.

Objective: To evaluate the role of SNP rs1834306 of miR100 and rs2910164 of miR146a in the development and prognosis of prostate cancer.

Methods: One hundred patients diagnosed with prostate cancer and 68 controls were selected. The identification of SNP was rated by quantitative polymerase chain reaction from blood samples, and the analysis was performed within the presence of SNP and the prognostic variables.

Results: In the SNP rs1834306 (miR100), a smaller presence of the polymorphic homozygous genotype was identified in patients with PSA >10 ng/mL, (P=0.03); when evaluating only the presence of the polymorphic allele G (P=0.09) it was compared to the presence of the wild type allele A. Among the patients with prostate cancer, SNP rs2910164 (miR146A), the polymorphic allele was more frequent in patients with a Gleason score ⩾7 than in patients with a Gleason score <7, (P=0.043). In patients with prostate cancer, miR100 was overexpressed in those with pT3 staging compared to pT2 and among those who had biochemical recurrence (P = 0.004 and P = 0.011, respectively).

Conclusions: SNP of miR146a acts as a poor prognostic factor (Gleason ⩾7), and the SNP of miR100 is linked to better prognostic data (PSA <10). MiR100 was overexpressed in prostate cancer with worse prognostic factors.

Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation.

Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases.

Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality.

Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels (P<0.001) and an increased percentage of patients with either portal vein thrombosis or tumor multifocality, each P<0.0001. Furthermore, the increases of both alpha-fetoprotein and portal vein thrombosis were proportionately greater than the related maximum tumor diameter increases. These trends of increased alpha-fetoprotein, portal vein thrombosis, and multifocality with increasing maximum tumor diameter had non-linear patterns. Within alpha-fetoprotein and multifocality trends, there were identifiable sub-trends associated with specific maximum tumor diameter ranges.

Conclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.

Background: Long non-coding RNA (lncRNA) PITPNA antisense RNA 1 (PITPNA-AS1) expression characteristics, function, and mechanism in papillary thyroid cancer are unclear.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for detecting PITPNA-AS1, UNC-5 netrin receptor B (UNC5B) mRNA, and miR-129-5p expressions in papillary thyroid cancer tissues and cell lines. EdU assay, cell counting kit-8 (CCK-8) assay, wound healing assay, and flow cytometry analysis were performed to investigate the biological functions of PITPNA-AS1 in papillary thyroid cancer. Dual-luciferase reporter assay was utilized for determining whether PITPNA-AS1 and miR-129-5p, as well as UNC5B and miR-129-5p could directly bind to each other. Western blot assay was employed for measuring UNC5B protein expression level in papillary thyroid cancer cell lines.

Results: PITPNA-AS1 and UNC5B expressions were markedly increased in papillary thyroid cancer tissues and cell lines while miR-129-5p expression was down-regulated. Knockdown of PITPNA-AS1 could significantly inhibit papillary thyroid cancer cell growth and migration and promote cell apoptosis while UNC5B overexpression plasmids or miR-129-5p inhibitors counteracted the knockdown effect of PITPNA-AS1 on papillary thyroid cancer cells. PITPNA-AS1 targeted miR-129-5p to repress its expression and miR-129-5p targeted UNC5B to repress its expression. Silencing PITPNA-AS1 reduced the expression of UNC5B via regulating miR-129-5p expression.

Conclusions: PITPNA-AS1 facilitated papillary thyroid cancer cell proliferation and migration, and suppressed apoptosis through miR-129-5p/UNC5B axis.

Background: BRCA1 and BRCA2 have been well studied for their roles in tumorigeneis, plus cancer diagnosis and treatment, but their prognostic value in colon cancer, especially for early-stage cancer, has not been fully illuminated. This study examined the expression levels of BRCA1 and BRCA2 proteins in sporadic colon cancer cases and investigated their value in prognosis.

Methods: The expression levels of BRCA1 and BRCA2 in 275 colon cancer patients who underwent radical surgeries were assayed by immunohistochemical staining in dissected tumor samples. Also, its correlation with clinicopathological characteristics, disease-free survival, and overall survival was investigated.

Results: Tumors with low expression levels of BRCA1, BRCA2, and both were 19.6%, 17.8%, and 6.5%, respectively. The levels of BRCA1/2 expression were not associated with clinicopathological parameters (gender, age, histological differentiation, and tumor node metastasis stage). Patients with low-levels of BRCA1 protein in their tumors demonstrated a lower chance of 5-year disease-free survival (55.6% vs. 69.7%, P=0.046), which was more obvious in the patients with stage I-II tumors without chemotherapy (52.6% vs. 82.6%, P=0.006). Neither BRCA1 nor BRCA2 affected overall survival in this cohort. Multivariate analysis revealed that pathologic stage and the level of BRCA1 protein were independent factors of long-term disease-free survival.

Conclusion: This study highlights BRCA1 as an independent prognosticator of early-stage colon cancer.

Background: microRNAs (miRNAs) are non-coding RNAs with important roles in the progression of human cancers, including gastric cancer. Exosomes are extracellular vesicles, which could transfer numerous noncoding RNAs, such as miRNAs. Here, in our study, we intended to investigate the role of exosomal miR-122-5p in gastric cancer progression.

Methods: Exosomes were isolated utilizing commercial kit or ultracentrifugation. Biomarkers of exosomes or epithelia-mesenchymal transition (EMT) were monitored by western blot. Expression levels of miR-122-5p and G-protein-coupled receptor kinase interacting protein-1 (GIT1) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation and apoptosis were assessed by colony formation assay, methyl thiazolyl tetrazolium assay and flow cytometry. Cell metastasis was evaluated via Transwell assay. The interaction between miR-122-5p and GIT1 was validated by dual-luciferase reporter assay. Furthermore, tumor growth in vivo was detected by xenograft assay.

Results: Exosomes were successfully isolated. MiR-122-5p was downregulated in exosomes derived from the serum of gastric cancer patients. Exosomal miR-122-5p could hinder gastric cancer cell proliferation and metastasis in vitro and tumor growth in vivo. Knockdown of GIT1 also inhibited gastric cancer cell proliferation and metastasis. Exosomal miR-122-5p targeted GIT1 to alter cellular behaviors of gastric cancer cells.

Conclusion: Exosomal miR-122-5p suppressed gastric cancer progression by targeting GIT1.

Background: Circulating tumor cells and serum tumor markers have been found significant in predicting outcome for several malignancies. However, their role in gastric cancer is not fully clarified. We conducted a retrospective study to explore the prognostic value of circulating tumor cells and their applicability in assessing the treatment efficacy in gastric cancers.

Methods: From September 2015 to December 2018, 116 patients with newly pathologically diagnosed gastric adenocarcinoma were enrolled. At both baseline and two courses after chemotherapy, the data of circulating tumor cells and serum tumor markers, such as CEA, CA72-4, CA19-9, CA50, and CA242, were collected. The relationships between the change trend of circulating tumor cells and the treatment efficacy were analyzed after chemotherapy, with a paired t-test. Univariate and multivariable analysis were used to find prognostic factors for overall survival (OS).

Results: We found there is a significant difference between the circulating tumor cells-positive and circulating tumor cells-negative before and after therapy (mOS 12.6 vs. 31.6 months, P<0.001; mOS 12.4 vs. 24.2 months, P=0.002), respectively. Also, differentiation, pre-therapeutic circulating tumor cells and therapeutic response were independent predictors of overall survival. Following two courses of chemotherapy, the number of circulating tumor cells increased obviously in the progressive disease group (P=0.002), while they decreased in the non-progressive disease group (P=0.02). Thus, the change in the circulating tumor cells count had a close association with the therapeutic response (P=0.004).

Conclusion: Generally, circulating tumor cells provide a novel tool to evaluate the outcomes of gastric cancer patients. Since the change of circulating tumor cells was highly related to treatment response, it may be an auxiliary to assess the effect of chemotherapy, leading an earlier adjustment of following regimens.

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Copy number variation (CNV) in several genetic regions correlate with cancer susceptibility. Hence, this study evaluated the association between CNV and non-small cell lung cancer (NSCLC) in the peripheral blood.

Methods: Blood samples of 150 patients with NSCLC and 150 normal controls were obtained from a bioresource center (Seoul, Korea). Through an epigenome-wide analysis using the MethylationEPIC BeadChip method, we extracted CNVs by using an SVS8 software-supplied multivariate method. We compared CNV frequencies between the NSCLC and controls, and then performed stratification analyses according to smoking status.

Results: We acquired 979 CNVs, with 582 and 967 copy-number gains and losses, respectively. We identified five nominally significant associations (ACOT1, NAA60, GSDMD, HLA-DPA1, and SLC35B3 genes). Among the current smokers, the NSCLC group had more CNV losses and gains at the GSDMD gene in chromosome 8 (P=0.02) and at the ACOT1 gene in chromosome 14 (P=0.03) than the control group. It also had more CNV losses at the NAA60 gene in chromosome 16 (P=0.03) among non-smokers. In the NSCLC group, current smokers had more CNV gains and losses at the ACOT1 gene in chromosome 14 (P=0.003) and at HLA-DPA1 gene in chromosome 6 (P=0.02), respectively, than non-smokers.

Conclusion: Five nominally significant associations were found between the NSCLC and CNVs. CNVs are associated with the mechanism of lung cancer development. However, the role of CNVs in lung cancer development needs further investigation.