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Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease, and 74 healthy individuals. All samples were randomly divided into a training set and a validation set. Carbohydrate antigen 19.9, CA242, POSTN, as well as carcinoembryonic antigen, were measured by ELISA or automated immunoassay. The receiver operating characteristic curve analysis revealed that the performance of CA19.9 in the validation group were improved by the marker panel composed of CA19.9, POSTN, and CA242, to discriminate early stage PDAC not only from healthy controls (area under the curve [AUC]CA19.9 = 0.94 vs AUCCA19.9 + POSTN + CA242 = 0.98, P < .05) but also from benign conditions (AUCCA19.9 = 0.87 vs AUCCA19.9 + POSTN + CA242 = 0.90, P < .05). In addition, POSTN retained significant diagnostic capabilities to distinguish PDAC CA19.9-negative from healthy controls (AUCPOSTN = 0.87) as well as from benign conditions (AUCPOSTN = 0.84) in the whole set. This study suggested that POSTN and CA242 are potential diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic cancer.

SUBMITTER: Dong D

PROVIDER: S-EPMC6125476 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

Dong Dong D Jia Li L Zhang Lufang L Ma Na N Zhang Aimin A Zhou Yunli Y Ren Li L

Cancer science 20180724 9

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the most frequently used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different s ...[more]

PMID: 29945294

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Project description:Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal common cancer because of late diagnosis. Novel biomarkers for PDAC early detection are urgently needed. tRNA-derived small RNAs (tsRNAs) are novel small RNAs might serve as biomarkers for cancer diagnosis and participate in diverse physiological and pathological process. We investigated whether the expression of tsRNAs in serum could be a noninvasive method in the early detection of PDAC. Blood sample of PDAC patients and healthy controls were collected from Ruijin Hospital, Shanghai, China. Tumor and adjacent normal pancreas tissues were collected from 51 patients with PDAC undergoing therapeutic surgery. The testing cohort comprised 6 PDAC patients and 6 healthy controls and the expression of small RNAs in serum was analyzed by small RNA sequence. We verified the diagnostic performance of serum tsRNAs by qPCR in validation cohort including 110 PDAC patients and 100 healthy controls. Expression level of tsRNAs in tissue was also verified in another independent cohort including 51 tumor and 51 adjacent normal pancreas tissues. Unpaired t-test and paired t-test are used for comparing depending on whether the samples are paired. The predictive performance of tsRNAs was evaluated by Kaplan-Meier survival and receiver operating characteristic (ROC) curve. There were 45 tsRNAs expressed at remarkably higher levels, 6 tsRNAs expressed at lower levels in PDAC patients, respectively, compared with healthy volunteers. tsRNA-ValTAC-41, tsRNA-MetCAT-37 and tsRNA-ThrTGT-23 expressed significant highly (P < 0.05) in serum of PDAC patients in validation cohort. tsRNA-ValTAC-41 or tsRNA-MetCAT-37 combined with CA19-9 could increase the AUC of PDAC prediction (AUC = 0.947 and 0.949 respectively), relative to CA19-9 test alone. Besides, patients with higher serum tsRNA-ValTAC-41 level showed shorter overall survival (OS). tsRNA-ValTAC-41 also expressed at remarkably higher level in tumor tissue, and it was obviously associated with tumor staging both in serum and tissue. We provide tsRNAs profiles observed by small RNA sequencing. The diagnostic accuracy of tsRNA-ValTAC-41 and tsRNA-MetCAT-37 in serum of PDAC patients were verified. Further studies for tsRNA-ValTAC-41 are needed to confirm the findings. These tsRNAs may be promising and effective candidates in the development of highly sensitive, noninvasive biomarkers for PDAC diagnosis.

Project description:The identification of new serum biomarkers with high sensitivity and specificity is an important priority in pancreatic cancer research. Through an extensive proteomics analysis of pancreatic cancer cell lines and pancreatic juice, we previously generated a list of candidate pancreatic cancer biomarkers. The present study details further validation of four of our previously identified candidates: regenerating islet-derived 1 beta (REG1B), syncollin (SYCN), anterior gradient homolog 2 protein (AGR2), and lysyl oxidase-like 2 (LOXL2).The candidate biomarkers were validated using enzyme-linked immunosorbent assays in two sample sets of serum/plasma comprising a total of 432 samples (Sample Set A: pancreatic ductal adenocarcinoma (PDAC, n?=?100), healthy (n?=?92); Sample Set B: PDAC (n?=?82), benign (n?=?41), disease-free (n?=?47), other cancers (n?=?70)). Biomarker performance in distinguishing PDAC from each control group was assessed individually in the two sample sets. Subsequently, multiparametric modeling was applied to assess the ability of all possible two and three marker panels in distinguishing PDAC from disease-free controls. The models were generated using sample set B, and then validated in Sample Set A.Individually, all markers were significantly elevated in PDAC compared to healthy controls in at least one sample set (p???0.01). SYCN, REG1B and AGR2 were also significantly elevated in PDAC compared to benign controls (p???0.01), and AGR2 was significantly elevated in PDAC compared to other cancers (p?<?0.01). CA19.9 was also assessed. Individually, CA19.9 showed the greatest area under the curve (AUC) in receiver operating characteristic (ROC) analysis when compared to the tested candidates; however when analyzed in combination, three panels (CA19.9?+?REG1B (AUC of 0.88), CA19.9?+?SYCN?+?REG1B (AUC of 0.87) and CA19.9?+?AGR2?+?REG1B (AUC of 0.87)) showed an AUC that was significantly greater (p?<?0.05) than that of CA19.9 alone (AUC of 0.82). In a comparison of early-stage (Stage I-II) PDAC to disease free controls, the combination of SYCN?+?REG1B?+?CA19.9 showed the greatest AUC in both sample sets, (AUC of 0.87 and 0.92 in Sets A and B, respectively).Additional serum biomarkers, particularly SYCN and REG1B, when combined with CA19.9, show promise as improved diagnostic indicators of pancreatic cancer, which therefore warrants further validation.

Project description:BackgroundMutant p53 protein overexpression has been reported to induce serum antibodies against p53. Various studies assessing the diagnostic value of serum p53 antibody in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of serum p53 antibody in esophageal cancer.MethodsWe systematically searched PubMed and Embase until 31st May 2012, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). The PLR and NLR and their 95% confidence interval (CI) were calculated using a fixed effects model according to the Mantel-Haensed method and random effects model based on the work of Der Simonian and laird, respectively.ResultsFifteen studies (cases?=?1079, controls?=?2260) met the inclusion criteria for the meta-analysis. Approximately 53.33% (8/15) of the included studies were of high quality (QUADAS score?8), which were retrospective case-control studies. The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of esophageal cancer were PLR 6.95 (95% CI: 4.77-9.51), NLR 0.75 (95%CI: 0.72-0.78) and DOR 9.65 (95%CI: 7.04-13.22). However, we found significant heterogeneity between NLRs.ConclusionsThe current evidence suggests serum p53 antibody has a potential diagnostic value for esophageal cancer. However, its discrimination power is not perfect because of low sensitivity.ImpactThese results suggest that s-p53-antibody may be useful for monitoring residual tumor cells and for aiding in the selection of candidates for less invasive treatment procedures because of the high specificity of s-p53-antibody. Further studies may need to identify patterns of multiple biomarkers to further increase the power of EC detection.

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Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

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Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

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