International Journal of Biological Markers最新文献

Background: The KRAS mutations are high-frequency somatic mutations found in colorectal cancer patients from Western and Asian countries however, with the exception of exon 2 of KRAS, other prevalence and prognostic values have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutations of KRAS in Chinese colorectal cancer patients and to investigate their impact on prognosis.

Methods: A total of 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing for detection of KRAS mutations. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at The Third Affiliated Hospital of Soochow University, China (sCohort) and used droplet digital™ polymerase chain reaction to detect KRAS mutations.

Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutations. The most frequent of these mutations were G12D (32.19%), G12V (17.96%), and G13D (17.59%). In the sCohort, 51 colorectal cancer patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%), and G14D (3.92%) were high-frequency. The KRAS mutations were associated with shorter median overall survival than wild-type tumors (69 vs. 55 months; HR 1.80; 95% Cl 1.22, 2.64; P=0.0003). In the Cox multivariate analysis, age (HR 1.562; 95% Cl 1.10, 2.22; P=0.013), tumor differentiation (HR 0.417; 95% Cl 0.19, 0.90; P=0.026), and KRAS mutation (HR 1.897; 95% Cl 0.19, 0.90; P=0.001) remained independent predictors of shorter overall survival. Among the common KRAS mutations, G12D was significantly associated with shorter overall survival (HR 2.17; 95% Cl 1.31, 3.58; P < 0.0001) compared with KRAS wild-type patients.

Conclusions: Our findings indicate that KRAS genes are frequently mutated, and over 30% harbored the KRAS G12D mutation subtype. We found that the KRAS G12D mutation is associated with inferior survival and is a biomarker of poor prognosis in Chinese patients. Our data emphasize the importance of molecular features in colorectal cancer patients, which could potentially be improved by G12D-specific related inhibitors.

Background: Recently, microRNA-221 has been found to be abnormally expressed in hepatocellular carcinoma; however, its clinical value has not been summarised. This meta-analysis aimed to assess the prognostic significance of miR-221 in hepatocellular carcinoma.

Material and methods: PubMed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, EMbase, Google Scholar, the Cochrane Library, CNKI, CBM, VIP and Wanfang databases were searched for eligible articles. The endpoints included overall survival, progression-free survival, recurrence-free survival, metastasis-free survival, disease-free survival. Hazard ratios with 95% confidence intervals were used to explore the relationship between miR-221 expression and clinical survival results of liver cancer patients. Subgroup analysis and sensitivity analysis were performed. Begg's test and Egger's test were conducted to evaluate publication bias.

Results: A total of nine studies including 607 patients were recruited for this meta-analysis. The pooled hazard ratios displayed that high miR-221 expression was remarkably associated with poorer overall survival (hazard ratio = 1.91, 95% confidence interval: 1.53-2.38, p ＜ 0.01) and unfavourable progression-free survival/recurrence-free survival/metastasis-free survival/disease-free survival (hazard ratio = 2.02, 95% confidence interval: 1.58-2.57, p ＜ 0.01). The results of Begg's test and Egger's test did not exhibit obvious publication bias.

Conclusions: High expression of miR-221 can predict poor outcome of hepatocellular carcinoma. miR-221 can be used as a promising prognostic biomarker of hepatocellular carcinoma.

Purpose: Serum bilirubin plays an important role in antioxidant and anticancer processes. The inverse association between serum bilirubin and cancer risk have been widely reported in multiple cancers. The aim of this retrospective study was to investigate the prognostic impact of serum bilirubin in colorectal cancer patients undergoing surgical resection.

Methods: The value of serum bilirubin including total bilirubin, direct bilirubin, and indirect bilirubin were tested at pre-operatively in 330 colorectal cancer patients. The optimal cut-off values for these three biomarkers were determined by X-tile program. The relationship between serum bilirubin and outcomes were examined using Kaplan-Meier curves log-rank test, univariate and multivariate cox regression. Moreover, a number of risk factors were used to form a nomogram for evaluating risk of survival.

Results: The optimal cut-off points of serum total bilirubin, direct bilirubin, and indirect bilirubin were 19.5 μmol/L, 5.0 μmol/L and 8.1 μmol/L, respectively. Elevated total bilirubin and direct bilirubin were significantly associated with overall survival in surgical colorectal cancer patients. Additionally, predictive nomogram including total bilirubin and direct bilirubin for overall survival was established for predicting overall survival in surgical colorectal cancer patients.

Conclusions: These findings indicated that preoperative elevated total bilirubin and direct bilirubin could be considered as independent prognostic biomarkers for poor overall survival of colorectal cancer patients.

Purpose: The study aims to provide a comprehensive account of the association of five MDM4 gene polymorphisms (rs1380576, rs1563828, rs10900598, rs11801299, and rs4245739) with susceptibility to cancer.

Methods: A literature search for eligible candidate gene studies published before 27 February 2021 was conducted in PubMed, Medline and Web of Science. The following combinations of main keywords were used: (MDM4 OR MDMX OR HDMX OR mouse double minute 4 homolog) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (cancer OR tumor OR neoplasm OR malignancy OR carcinoma OR adenocarcinoma). Potential sources of heterogeneity were sought out via meta-regression, subgroup and sensitivity analysis.

Results: Overall, a total of 15 articles with 21,365 cases and 29,280 controls for five polymorphisms of the MDM4 gene were enrolled. In the stratified analysis of rs1380576, we found that Asians might have less susceptibility to cancer. We found that rs4245739 was correlated with a decreased risk of cancer for Asians and breast cancer susceptibility. However, for other polymorphisms, the results showed no significant association with cancer risk.

Conclusion: MDM4 rs1380576 polymorphism is negatively associated with the risk of cancer in the Asian population. MDM4 rs4245739 polymorphism is inversely associated with cancer risk for Asians and breast cancer susceptibility.

Objective: Our study aimed to observe and evaluate the clinical value of interleukin (IL)-11 in the serum and exhaled breath condensate of patients with non-small cell lung cancer (NSCLC).

Methods: A total of 91 patients with NSCLC and 72 healthy volunteers were included in this study. IL-11 concentration was determined by ELISA, and the relationship between IL-11 expression in serum and exhaled breath condensate specimens, and the clinicopathological characteristics of patients with NSCLC were analyzed. The relationship between serum IL-11 expression and traditional tumor markers and inflammation indicators of NSCLC was also analyzed. The correlation between serum IL-11 and exhaled breath condensate IL-11 level was determined. The receiver operating characteristic curve was used to evaluate the diagnostic value of IL-11 and carcinoembryonic antigen single and combined detection for NSCLC. The published data from online databases were used to analyze the relationship between the expression of IL-11 and the prognosis of NSCLC.

Results: IL-11 concentration in serum and exhaled breath condensate specimens of patients with NSCLC were significantly increased. IL-11 expression was positively correlated with lymph node metastasis, distant metastasis, tumor node metastasis stage, and tumor differentiation degree of NSCLC. The expression of IL-11 in serum was positively correlated with that in exhaled breath condensate specimens. IL-11 expression was closely related to that of neutrophil-to-lymphocyte ratio and carcinoembryonic antigen. The combination of serum IL-11 with exhaled breath condensate IL-11 and carcinoembryonic antigen showed significantly higher diagnostic value than any one marker alone. Besides, the high IL-11 expression was closely related to the poor prognosis of NSCLC.

Conclusion: IL-11 can be used as a potential diagnostic and prognostic biomarker for NSCLC.

Background: Cluster of differentiation molecules are markers of immune cells that have been identified as a potential immunotherapeutic target for cancer treatment. MicroRNAs are small non-coding RNAs that act as tumor suppressors or oncogenes whose importance in diagnosis, prognosis, and treatment of gastric and colorectal cancers has been widely reported. However, their association with cluster of differentiation molecules in gastrointestinal cancers has not been well studied. Therefore, our study aimed to analyze the relationship between microRNAs and cluster of differentiation molecules in gastrointestinal cancers, and to identify cluster of differentiation molecule-associated microRNAs as prognostic biomarkers for gastrointestinal cancer patients.

Methods: Targetscan, Starbase, DIANA microT, and miRDB were used to investigate microRNA profiles that might be correlated with cluster of differentiation molecules in gastrointestinal cancers. Moreover, The Cancer Genome Atlas data analysis was used to investigate the association between cluster of differentiation molecules and microRNA expression in patients with gastric, colon, rectal, pancreatic, and esophageal cancers. The Kaplan-Meier plotter was used to identify the association between overall survival and cluster of differentiation molecule-associated microRNA expression in gastrointestinal cancer patients.

Results: miR-200a, miR-559, and miR-1236 were negatively associated with CD86, CD81, and CD160, respectively, in almost all types of gastrointestinal cancers, which were further verified in the in vitro studies by transfecting microRNA mimics in gastric cancer, colon cancer, pancreatic, and esophageal cell lines.

Conclusion: Our study showed that miR-200a, miR-1236, and miR-559 are identified as cluster of differentiation-associated microRNAs in gastrointestinal cancers, providing a novel perspective to identify new therapeutic targets for cancer immunotherapy in gastrointestinal cancer patients.

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.