The clinical utility of CA125/MUC16 in pancreatic cancer: A consensus of diagnostic, prognostic and predictive updates by the Chinese Study Group for Pancreatic Cancer (CSPAC)

  • Authors:
    • Liang Liu
    • Jinfeng Xiang
    • Rufu Chen
    • Deliang Fu
    • Defei Hong
    • Jihui Hao
    • Yixiong Li
    • Jiangtao Li
    • Shengping Li
    • Yiping Mou
    • Gang Mai
    • Quanxing Ni
    • Li Peng
    • Renyi Qin
    • Honggang Qian
    • Chenghao Shao
    • Bei Sun
    • Yongwei Sun
    • Min Tao
    • Bole Tian
    • Hongxia Wang
    • Jian Wang
    • Liwei Wang
    • Wei Wang
    • Weilin Wang
    • Jun Zhang
    • Gang Zhao
    • Jun Zhou
    • Xianjun Yu
  • View Affiliations

  • Published online on: December 30, 2015     https://doi.org/10.3892/ijo.2015.3316
  • Pages: 900-907
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Abstract

The prognosis for pancreatic cancer (PC) is poor; however, the timely and accurate treatment of this disease will significantly improve prognosis. Serum biomarkers involve non-invasive tests that facilitate the early detection of tumors, predict outcomes and assess responses to therapy, so that the patient can be continuously monitored and receive the most appropriate therapy. Studies have reported that cancer antigen (CA)125 [also known as mucin 16 (MUC16)] has functional significance in the tumorigenic, metastatic and drug resistant properties of PC. Our aim was to use this biomarker in the diagnosis, detection of metastasis, prognosis and in the monitoring of the treatment effects of PC. Members of the Chinese Study Group for Pancreatic Cancer (CSPAC) reviewed the literature on CA125/MUC16 and developed an objective consensus on the clinical utility of CA125/MUC16 for PC. They confirmed the role of CA125/MUC16 in tumorigenesis and the progression of PC, and recommended monitoring CA125/MUC16 levels in all aspects of the diagnosis and treatment of PC, particularly those that involve the monitoring of treatments. In addition, they suggested that the combination of other biomarkers and imaging techniques, together with CA125/MUC16, would improve the accuracy of the clinical decision-making process, thereby facilitating the optimization of treatment strategies. Periodic clinical updates of the use of CA125/MUC16 have been established, which are important for further analyses and comparisons of clinical results from affiliates and countries, particularly as regards the in-depth biological function and clinical translational research of this biomarker.

Introduction

Pancreatic cancer (PC) remains one of the most lethal malignancies, with an extremely poor prognosis. Individualized treatment based on the accurate evaluation of the disease is urgently required. The traditional method of pre-treatment assessment relies on the tumor-node-metastasis (TNM) staging system, which usually relies on imaging tests. The goal of serum cancer biomarker studies is to develop simple non-invasive tests, with or without the use of other techniques, in order to better characterize tumorigenesis. This may facilitate the early detection of tumors for cancer prognosis, the classification of tumors, and the determination of therapeutic effects, so that the clinician can monitor disease progression, regression and recurrence, in order to help patients receive the most appropriate therapy (1). Cancer antigen (CA)19-9 is the most commonly used biomarker for the diagnosis, prognosis and the therapeutic monitoring of PC. However, the sensitivity and specificity limit its applicability in many cases. CA125/mucin 16 (MUC16) is a transmembrane mucin, which was originally detected in epithelial cells and mucus layers of the respiratory and gastrointestinal tracts (2,3). The serum levels of CA125 have been widely used in ovarian cancer for diagnosis, the detection of early recurrence, and for the monitoring of the therapeutic effects of treatments (46). Recently, studies on the use of CA125/MUC16 in patients with PC treated with resection, radiotherapy or chemotherapy have been published, and may assist in the diagnosis and treatment of this type of cancer (79). The Chinese Study Group for Pancreatic Cancer (CSPAC) has provided a consensus on the use of the biomarker CA125/MUC16, its biological significance and its clinical applicability, in order to facilitate the optimization of treatment strategies for PC.

Materials and methods

The consensus described in this study was conducted by CSPAC. All participating experts are specialists from high volume centers with long-term experience in pancreatic surgery, oncology and scientific research.

Evidence acquisition and synthesis

The inclusion and exclusion criteria for evidence acquisition and synthesis are listed in Table I. A systematic literature search of the PubMed database was performed using the following keywords: ‘pancreatic cancer, ‘pancreatic adenocarcinoma’, ‘CA125’, ‘MUC16’, ‘diagnosis’, ‘prognosis’, ‘predictive factor’, ‘prognostic factor’ and ‘survival’. Studies published between the years 2000–2015 were reviewed and selected for further screening analyses and for subsequent consensus studies. The reference lists of the retrieved literature were also cross-searched for additional publications. Only studies published in the English language were included. Overall, 143 reports published between 2000–2015 were retrieved with the consensus of all authors. As the main findings of some studies deviated from the purpose of the consensus, we performed a primary screening based on content browsing, and subsequently exchanged views concerning the primary screening. Finally, 72 reports were selected for further review. due to the paucity of large sample randomized data, studies were finally selected based on the following criteria: the derivation and evolution of relevant concepts, long-term clinical observations and variable and multivariable statistical analyses.

Table I

Inclusion and exclusion criteria for literature review.

Table I

Inclusion and exclusion criteria for literature review.

Criteria
Inclusion criteria
 Including keywords in all fields‘Pancreatic cancer’, ‘pancreatic adenocarcinoma’, “CA125', ‘MUC16’, ‘diagnosis’, ‘prognosis’, ‘predictive factor’, ‘prognostic factor’ and ‘survival’
 Writing languageEnglish
 Publication dateFrom 2000 to 2015
 Highlights and contents conform with the purpose of consensusDerivation and evolution of relevant concepts; long-term clinical observation; variable and multivariable statistical analyses
Exclusion criteria
 Highlights and contents deviate from the purpose of consensus
 Disagreement and controversyFail to pass the cross-talk between experts or more than half exchanged views are inconsistent at the time of primary screening
 Sample capacityCase report or sample size is <50

Studies were selected based mainly on 4 categories: diagnostic significance, predictive significance, prognostic significance and therapeutic monitoring significance. A detailed description of the final selected reports (associated with clinical application rather than pure basic research in PC) is presented in Table II. Due to the lack of studies concerning CA125/MUC16 and its use in PC, only a limited amount of data were available. However, several single-institutional and multi-institutional studies were published that provided meaningful information on diagnostic, prognostic and predictive updates of patients with PC. Several promising combined biomarkers were also evaluated; however, further studies are warranted in order to accurately determine their clinical significance.

Table II

Summary of the available literature on the relevant clinical significance of serum levels of CA125 in pancreatic cancer.

Table II

Summary of the available literature on the relevant clinical significance of serum levels of CA125 in pancreatic cancer.

CA19-9CA125CA19-9 + CA125



ClassificationAuthors/(Ref.)YearCountry/regionSample sizeSensitivity (%)Specificity (%)Sensitivity (%)Specificity (%)Sensitivity (%)Specificity (%)
Diagnostic significanceChan et al (36)2014Pittsburgh, PA, USA40077.583.170.375.181.187.7
Wang et al (79)2013Beijing, China14573.385.730.788.6--
Liu et al (42)2014Shandong, China705------
O'Brien et al (34)2015UK56575.0/37.5a92.6/96.2a41.7/12.5a96.3/96.2a83.3/43.8a88.9/92.3a
Yang et al (80)2014Beijing, China913------
Nolen et al (81)2014Pittsburgh, PA, USA67521.8b-6.67b---
Duraker et al (56)2007Turkey18181.375.956.977.6--
Cwik et al (34)2006Poland11080.889.160.883.387.877.8
Predictive significanceOkada et al (9)2014Japan20040.858.569.171.3--
Luo et al (37)2013Shanghai, China21263.2471.0578.6871.05--
Prognostic significanceChen et al (52)2015Shanghai China211------
Chang et al (822009USA9580.0-----
Chen et al (8)2014Henan, China6293.593.574.2100--
Liu et al (7)2015Shanghai, China709cccccc
Treatment monitoringChen et al (52)2015Shanghai, China211------
Shi et al (48)2015Shanghai, China60------

{ label (or @symbol) needed for fn[@id='tfn1-ijo-48-03-0900'] } The comparison results in these studies are all between pancreatic ductal adenocarcinoma (PDAC) and benign pancreatic diseases.

a The numbers before and after the separatrix, respectively refer to the sensitivity or specificity in 0–0.5 and 0.5–1 years prior to diagnosis (CA19-9>37 U/ml; CA125>30 U/ml).

b Sensitivity at 95% specificity.

c These studies in particular perfomred a more extensive subgroup analysis to find that the panel of tumor markers (CEA+/CA125+/CA19-9 ≥1,000 U/ml) could independently predict the non-decrease in CA19-9 levels post-operatively and were closely associated with a poor surgical outcome.

All CSPAC participants reviewed all the relevant reports and contributed to the consensus. Draft versions were circulated among the participants over a period of 3 months, and all comments and suggestions were considered before all the CSPAC participants agreed to a final consensus statement.

Results

Molecular characteristics and functional significance of CA125/MUC16

CA125 is a repeating peptide epitope of the mucin MUC16, which is a large, complex glycoprotein (10). There are a number of repeats in the tandem repeat region (18–60 amino acids) that result in various isoforms of MUC16 and confer functional heterogeneity (11). MUC16 undergoes continuous glycosylation and deglycosylation throughout its presence in bodily fluids, leading to significant heterogeneity in both size and charge (12). In addition, the glycosylated region potentially interacts with other glycosylated proteins to activate various signaling pathways (13). Furthermore, the levels of CA125/MUC16 show a correlation with immunological responses, proliferation and migration pathways in both physiological and pathological conditions (14,15). Under normal biological conditions, MUC16 is expressed in the epithelial lining, where its primary functions are to provide hydration and lubrication (16). Studies have analyzed the specific role of CA125/MUC16 in various types of cancer (2,1721). In breast cancer cells, MUC16 has been shown to interact with Janus kinase 2 (JAK2) and phosphorylates signal transducer and activator of transcription 3 (STAT3), eventually increasing the transcription of cyclin D1 for cell proliferation (18). CA125/MUC16 can affect the formation of the glycocalyx by interacting with galectin 1 and 3 in normal epithelial cells. However, in cancer cells, this enhanced interaction facilitates cancer progression (22). The MUC16-mesothelin interaction in ovarian cancer and PC cells leads to the upregulation of matrix metalloproteinase (MMP)-7 expression by increasing the phosphorylation of p38 mitogen-activated protein kinase (MAPK), activating cell invasion and migration (23). These studies have demonstrated the context-dependent function of CA125/MUC16 in organ development, cancer cell proliferation, metastasis, the regulation of immune responses and in anticancer therapeutic effects. From these data, tumors are now classified based on their molecular phenotype and not solely on their histological attributes. For example, the overexpression of CA125 on the cell surface has already been identified in heterogeneous malignant diseases, such as ovarian cancer, lung cancer, uterine cancer, gastrointestinal cancer and PC, and has become an important marker for tumor management (2326).

The clinical applicability of CA125/MUC16 assays has resulted from basic, translational and clinical studies for over three decades. The serum levels of CA125 are commonly monitored in patients with ovarian cancer, and an increase over an individualized baseline concentration is a prognostic indicator of cancer recurrence (6). Although CA125 has often been used for the diagnosis of ovarian cancer, the measurement of the levels of CA125/MUC16 is also valuable in other types of cancer, and numerous large-scale clinical trials have been conducted or are underway to determine the possible use of CA125/MUC16 as a biomarker in many other solid cancers (7,1921,27).

Use of CA125/MUC16 for the diagnosis of PC

The clinical stage of the disease at diagnosis often determines the prognosis and survival rate of a patient with PC (28). The early symptoms of PC are not always obvious on imaging (ultrasound or computed tomography), and when patients present with weight loss, jaundice, abdominal pain and other symptoms, they are usually already in the advanced stages of PC (29). However, the detection of different tumor markers, such as CA125, with appropriate sensitivity or specificity, may facilitate early diagnosis and provide a meaningful parameter in gastrointestinal tumors (27,30,31).

The conventional view is that tumor biomarkers, such as CA19-9 and CA125 are upregulated late in the course of PC development (32,33). However, recent studies have reported that CA19-9 and CA125 can be detected up to 1–2 years prior to diagnosis, and that the combination of CA19-9 and CA125 can improve the diagnostic sensitivity, as elevated CA125 levels are not only observed in CA19-9-positive cases, but also in approximately 20% of CA19-9-negative cases. Moreover, their preclinical levels (the cut-off value of CA125 is 30 U/ml, Table II) also correlate with prognosis, which demonstrate its value for the preclinical evaluation of PC (34). CA19-9 is a classical serum biomarker commonly used in pancreatic ductal adenocarcinoma (PDAC). Its sensitivity and specificity for diagnosis are 79–81 and 82–90%, respectively (32). However, a common problem involves false-positive results found in benign pancreaticobiliary diseases, such as pancreatitis, obstructive jaundice and cholangitis (33,35). In these patients, serum levels of CA125 provide a valuable contribution in the diagnosis of differentiating malignant and benign pancreatic diseases (33). The sensitivity and specificity for serum CA125 are 41.7–70.3 and 75.1–96.3% (Table II), respectively (34,36). However, CA125 also has a rare diagnostic value in cases where CA19-9 is not elevated, particularly in those patients who are negative for Lewis antigen (34). The most commonly used cut-off value of CA125 is approximately 30–35 U/ml (5,37); however, other studies have reported that a lower level of CA125 may also have significance for diagnosis (7,9,34,38).

Distant metastasis at the time of diagnosis is a major reason for a poor prognosis, and is considered the major obstacle to the effective use of surgery as a treatment option. Surgeons sometimes encounter distant metastases intraoperatively, including tiny liver metastases or a small amount of peritoneal metastases, which are difficult to detect pre-operatively using recently developed imaging techniques (39,40). The traditional strategy uses pre-operative chemotherapy or chemoradiotherapy after the identification of patients who are unlikely to benefit from resection. If metastasis occurs during treatment, it is a time-consuming process, which may delay an optimal surgical outcome (41,42). In addition, the follow-up period is sometimes inadequate to treat metastasis effectively. Studies have reported that the measurement of a series of tumor markers [CA19-9, CA125, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA242, CA72-4, CA50, CA15-3, and the beta-subunit of human chorionic gonadotropin (hCG-β)] improves the early diagnosis of cancer (36,43). CA125/MUC16 is aberrantly expressed in various types of cancer, and it can promote proliferation, migration and metastasis by facilitating metastatic and invasive gene transcription (23,44,45). Increasing preclinical studies have reported that CA125 levels are closely related with distant metastasis (39,46). However, due to its limited specificity, the measurement of a single tumor marker is usually not sufficient to accurately diagnose cancer (31).

Consensus statement

We recommend the use of CA125 for diagnosis (including metastasis and differential diagnosis between benign and malignant diseases), particularlyy in cases which are CA19-9-negative. Simultaneous assessments, including various biomarkers, oncogenomic analyses and functional imaging tests, such as positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18FDG PET/CT) are important for the accurate diagnosis of PC (4750).

Special applications during jaundice and effusion

Tumor marker levels may show false-positives in some benign diseases or complications, which can lead to the overestimation or to confusion regarding the actual condition of the disease. Hepatobiliary disease and renal failure are commonly associated with false-positive results (43,51). Compared to patients with benign jaundice, patients with malignant jaundice have higher levels of CA19-9, which do not significantly decrease even after drainage (52). CA19-9 has a better sensitivity; however, CA125 and CEA have higher specificities than CA19-9 for the diagnosis of patients with malignant tumors (52). Nonetheless, the use of serum CA19-9 levels alone is not always reliable in patients with hyperbilirubinemia and the CA19-9 non-secreter phenotype. CA19-9 levels can be affected by hyperbilirubinemia, which induces an increase in serum levels. Furthermore, we recently found that there is little or no correlation between CA125 and serum bilirubin levels (less affected by relieving jaundice) (53). Thus, CA125, but not CA19-9, may be more stable, and could more accurately predict the prognosis of patients with PDAC with hyperbilirubinemia (53). Certain studies have also suggested that serum CA125 levels vary in different types of effusions, and that the levels are closely related to peritoneal metastasis (38,54).

Consensus statement

We recommend using CA125 levels to assist in clinical diagnosis and preclinical prediction as a supplement to CA19-9 levels, particularly in some special conditions, such as hyperbilirubinemia. A second or third cut-off for serum CA125 levels (concentrations of more or less than the commonly used value of 35 U/ml) should be considered if necessary (5557).

Predictive and prognostic use of serum CA125 in pre-treatment evaluation
Predicting surgical outcomes prior to surgery and use as a guide for pre-operative or post-operative comprehensive treatment strategies

Previous studies have reported that CA19-9 can assist in assessing the resectability of PC by using three-dimensional computed tomography (CT) reconstruction (5861). We previously reported that CA125 was superior to CA19-9 in predicting the resectability of PC (38). Aberrantly high levels of CA125 may indicate unresectable PC, even for patients diagnosed by CT as being resectable. Moreover, in the assessment of the therapeutic effects to the patient after surgery, we found that a subset of patients with post-operatively decreased CA19-9 levels would have a survival advantage. We also identified a series of tumor markers (CEA+/CA125+/CA19-9 ≥1,000 U/ml) which could independently predict the post-operative maintenance of elevated CA19-9 levels, and were closely associated with poor surgical outcomes, in order to select appropriate therapies for patients with PC before treatment (7). The treatment of PC is increasingly multimodal; therefore patients receive chemotherapy or chemoradiation pre-operatively or post-operatively in order to achieve long-term benefits (29,62). Current guidelines support a neoadjuvant strategy for patients with locally advanced and borderline resectable disease (63). However, the necessity of these treatments is still controversial for PC due to the complexity and presence of a possibly latent preoperative metastatic disease, making it difficult to judge whether a patient would benefit from a particular treatment, particularly for borderline resectable patients (64). For patients with resectable and borderline resectable PC, recent studies have evaluated the necessity and efficacy of neoadjuvant therapy based on pre-treatment assessments (65,66). Serum biomarkers (CA19-9, mesothelin, and CA125) have proven to be effectively able of identifying patients who harbor micrometastatic disease. These patients should therefore receive neoadjuvant chemotherapy, thus sparing them from the potential morbidities associated with unnecessary radiation or surgery (23,67).

Predictive prognosis indicating post-operative recurrence and metastasis

The pre-operative CA125 level is a useful predictive biomarker for curative resection, and is a prognostic biomarker for recurrence in various types of cancer (epithelial ovarian carcinoma, breast cancer and lung cancer) (4,68,69). A recent study indicated that CA125 is an independent prognostic factor for gastric cancers, and an independent predictor of peritoneal metastasis (27). Patients with elevated serum CA125 levels, as compared to those with normal serum CA125 levels, have significantly higher incidences of peritoneal metastasis (39). Moreover, elevated CA125 levels also indicate a lower 5-year overall survival rate in patients with gastrointestinal cancer (39,70). In our previous study, we also found that CA125 expression was much higher in metastatic lesions and was related with the metastasis-associated burden. When 18F-FDG PET/CT was not available, we used CA19-9 and CA125 levels to establish equations for metabolic tumor volume (MTV) and total lesion glycolysis (TLG) based on their functional properties reflecting metabolic tumor burden. Our results suggested that the metabolic tumor burden estimated by serum tumor biomarkers may be suitable for monitoring the response to treatment and the progression of PC (49). Recently, we reported that pre-operative CA125 levels can predict post-operative early recurrence (Liu et al, unpublished data). In addition, another recent study revealed the co-expression of CA125 and mesothelin in PC, which was associated with a poor prognosis due to the related initiation of intracavitary tumor metastasis (23). Not only CA125 alone, but other serum tumor biomarkers such as CA242, CA19-9 and CEA, when used as prognostic tools, may also be of great clinical value for the efficacy and prognosis of specific treatments for patients with PC, with the possibility of recurrence and metastasis (8).

Consensus statement

We recommend the pre-operative detection of CA125 levels in serum. Patients with high pre-operative CA125 levels need to be alerted to the presence of microsystemic metastases. Moreover, patients with high pre-operative CA125 levels also need close follow-up after surgery and active post-operative adjuvant treatment to prevent possible future recurrence and metastasis. For those patients with significantly abnormal levels of CA125 prior to surgery, particularly those with CEA+/CA125+/CA19-9 ≥1,000 U/ml, a multidisciplinary comprehensive treatment is recommended and an active neoadjuvant therapy should be performed when microsystemic metastases is highly suspected. However, this strategy requires additional data from further evidence-based medical studies, so additional prospective clinical trials are urgently required.

The value of monitoring therapeutic effects during follow-up

The serum CA125 level is routinely used in ovarian cancer to monitor the effectiveness of therapy (6,71). In addition, it is widely used during follow-up to identify a subgroup of patients with dormant recurrence (46). A previous study demonstrated an association between the dynamic changes in CA125 levels, tumor size reduction, the remission of clinical symptoms and chemotherapeutic effects (6). Additional studies have indicated that the elevation in the serum levels of CA125 correlate with cancer progression and treatment effects (72,73). Our team previously showed a better efficacy for CA125 compared with CA19-9 levels in determining the resectability of PC (38). Moreover, we recently demonstrated that CA125 was closely associated with the metastatic tumor burden and disease progression in patients with PC (Liu et al, unpublished data). Measuring the serum CA125 level may provide a useful index for determining the course of PC and for monitoring the therapeutic effects.

Consensus statement

We recommend that CA125 monitoring should be used for patients during follow-up to monitor the disease course and therapeutic effects, to assist in evaluating the curative effects, and to adjust the treatment strategy.

The value of combined applications with other biomarkers and metabolic imaging

Due to limited sensitivity and specificity, the measurement of a single tumor biomarker is usually not sufficient to evaluate tumor development (30,74). Certain studies have indicated that the serum levels of individual biomarkers, such as CA125, CEA, CA19-9, and CA242 are not associated with tumor size (8). However, patients with high expression levels of these markers presented with late-stage disease, which demonstrated that a comprehensive assessment of various biomarkers, to provide more biological information, was necessary (8,31,43). In previous studies, the multi-analysis of different biomarkers [CA19-9, neuron specific enolase (NSE), CEA, CA242, CA125, circulating tumor cells and ctDNA] was more useful in the diagnosis and prognosis of PC, and was superior to that of any single biomarker (75,76). Currently, PET has been widely used in clinical practice to improve diagnosis and regular reexamination by detecting metastasis, even when it is slight and asymptomatic (77,78). We recently proposed a promising method for the pre-operative prediction of the prognosis of patients with PC using the combination of 18F-FDG PET/CT and serum CA19-9 levels (47). Due to the important role of CA125 for the diagnosis, prognosis and course monitoring of PC, the combination of serum CA125 and metabolic imaging with 18F-FDG PET/CT may be effective, but requires further validation.

Consensus statement

We recommend that the combination of CA125 and other serum/tissue biomarkers, or similar combined applications, such as CA19-9 levels along with 18FDG PET/CT are important for the diagnosis, treatment and surveillance of patients with PC at follow-up.

Discussion

All recommendations were created based on the literature reviews of basic and clinical studies by all authors of this consensus study. The retrieved results originated from the PubMed database, and were all reviewed in detail. Due to the limited number of contributors, a possible bias may exist. In addition, it is noteworthy that although the authors selected the studies to be included based on the criteria mentioned herein, a selection bias may have occurred due to the lack of reported randomized trials. However, previous and ongoing studies have indicated that there is a novel hypothesis concerning the clinical use of CA125/MUC16 levels in many aspects of PC management. This study evaluated these common results and extracted recommendations for future studies.

Within the present CSPAC consensus statement, CA125/MUC16 has been verified as useful for diagnosis, the detection of metastasis, predicting prognosis and monitoring the therapeutic effects of PC treatments, which may be helpful for selecting the appropriate therapy and monitoring disease progression, regression and recurrence. In particular, the data support the hypothesis that CA125/MUC16 plays an oncogenic and metastasis-predictive role in the progression of PC, and correlates with the metastatic tumor burden. Although the most commonly used cut-off value of CA125 is 30–35 U/ml (5,37), data indicate that a lower level of CA125 may have a significant diagnostic or predictive value for PC (34,38). In some cases, a second or third cut-off value (concentrations less or more than 35 U/ml CA125) is recommended (5557). However, evaluations using a single biomarker are less effective; therefore, the use of CA125/MUC16 levels may complement the use of CA19-9 levels and imaging tests, such as PET/CT. The importance of CA125/MUC16 in PC suggests the need for additional studies on biological functions and clinical translation. As shown in our studies, the combination of various serological biomarkers (CA125+/CEA+/CA19-9 ≥1,000 U/ml) and metabolic imaging may be more useful in the evaluation of patients with PDAC and ultimately may promote the development of precise individualized treatment options (7,47).

Acknowledgements

We would like to thank Huaxiang Xu, WenQuan Wang, Chuantao Wu, Zihao Qi, Jin Xu, Chen Liu, Jiang Long, Bo Zhang, Huanyu Xia and Guopei Luo for their preliminary work for the consensus. We would also like to thank Bioscience Writers, LLC (8418 Bluegate St., Houston TX 77025, USA) for their assistance in editing this manuscript. This study was supported by the National Natural Science Foundation of China (81402397, 81472670, 81402398 and 81172005), the National Natural Science Foundation of Shanghai (14ZR1407600), the ‘Yang-Fan’ Plan for Young Scientists of Shanghai (14YF1401100), Ph.D. Programs Foundation of Ministry of Education of China (20110071120096).

Abbreviations:

PC

pancreatic cancer

TNM

tumor-node-metastasis

CA

cancer antigen

MUC16

mucin 16

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March 2016
Volume 48 Issue 3

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APA
Liu, L., Xiang, J., Chen, R., Fu, D., Hong, D., Hao, J. ... Yu, X. (2016). The clinical utility of CA125/MUC16 in pancreatic cancer: A consensus of diagnostic, prognostic and predictive updates by the Chinese Study Group for Pancreatic Cancer (CSPAC). International Journal of Oncology, 48, 900-907. https://doi.org/10.3892/ijo.2015.3316
MLA
Liu, L., Xiang, J., Chen, R., Fu, D., Hong, D., Hao, J., Li, Y., Li, J., Li, S., Mou, Y., Mai, G., Ni, Q., Peng, L., Qin, R., Qian, H., Shao, C., Sun, B., Sun, Y., Tao, M., Tian, B., Wang, H., Wang, J., Wang, L., Wang, W., Wang, W., Zhang, J., Zhao, G., Zhou, J., Yu, X."The clinical utility of CA125/MUC16 in pancreatic cancer: A consensus of diagnostic, prognostic and predictive updates by the Chinese Study Group for Pancreatic Cancer (CSPAC)". International Journal of Oncology 48.3 (2016): 900-907.
Chicago
Liu, L., Xiang, J., Chen, R., Fu, D., Hong, D., Hao, J., Li, Y., Li, J., Li, S., Mou, Y., Mai, G., Ni, Q., Peng, L., Qin, R., Qian, H., Shao, C., Sun, B., Sun, Y., Tao, M., Tian, B., Wang, H., Wang, J., Wang, L., Wang, W., Wang, W., Zhang, J., Zhao, G., Zhou, J., Yu, X."The clinical utility of CA125/MUC16 in pancreatic cancer: A consensus of diagnostic, prognostic and predictive updates by the Chinese Study Group for Pancreatic Cancer (CSPAC)". International Journal of Oncology 48, no. 3 (2016): 900-907. https://doi.org/10.3892/ijo.2015.3316