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Licensed Unlicensed Requires Authentication Published by De Gruyter April 12, 2018

Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations

  • Željko Debeljak EMAIL logo , Sandra Dundović , Sonja Badovinac , Sanja Mandić , Miroslav Samaržija , Branko Dmitrović , Marija Miloš , Lana Maričić , Vatroslav Šerić and Vikica Buljanović

Abstract

Background:

Carbohydrate sulfotransferases (CHST) were shown to be involved in carcinogenesis. The aim of the study was to assess the diagnostic value of serum CHST7 concentration in differentiation between lung cancer and non-malignant pulmonary inflammations.

Methods:

Clinical case-control study involving 125 participants was conducted: the control group containing cases of pneumonia and chronic obstructive pulmonary disease was compared to the lung cancer group composed of primary and metastatic cancers. Serum concentrations of CHST7 and routinely used markers including carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA 21-1) and neuron-specific enolase (NSE) were determined for each participant using immunochemical methods. Statistical association, receiver operating characteristic (ROC) analysis and cross-validation were used for the evaluation of CHST7 either as a standalone biomarker or as a part of a biomarker panel.

Results:

In comparison to the control group, serum CHST7 was elevated in lung cancer (p<0.001), but no differences between the overall stages of primary cancers were detected (p=0.828). The differentiation performance in terms of ROC area under curve (AUC) was 0.848 making CHST7 superior biomarker to the NSE (p=0.031). In comparison to CEA and CYFRA 21-1, the performance differences were not detected. CHST7 was not correlated to other biomarkers, and its addition to the routine biomarker panel significantly improved the cross-validated accuracy (85.6% vs. 75.2%) and ROC AUC (p=0.004) of the differentiation using a machine learning approach.

Conclusions:

Serum CHST7 is a promising biomarker for the differentiation between lung cancer and non-malignant pulmonary inflammations.


Corresponding author: Assist. Prof. Željko Debeljak, PhD, Institute of Clinical Laboratory Diagnostics, Osijek University Hospital, Josipa Huttlera 4, 31 000Osijek, Croatia, Phone: +385 31 511 650

Acknowledgments

The authors would like to thank Dario Mandić and Mirjana Fijačko, Osijek University Hospital, Croatia; Mirjana Horvat, Našice General Hospital, Croatia; and Dunja Buljubašić, Blekingesjukhuset, Karlshamn, Sweden, for assistance in sample collection and in ELISA measurements. The authors would also like to thank Larisa Miller, Sanofi Genzyme, USA, for useful comments and suggestions.

  1. Author contributions: ŽD, SD, BD and SB conceived and designed the experiments. SD, ŽD, SM, SB and MM performed the experiments. ŽD, SD, SM, SB, LM and MS analyzed the data. ŽD, VŠ, VB and MS coordinated the research. VŠ and VB contributed reagents, materials and analysis tools. ŽD, SM, SB and SD wrote the manuscript. MM, MS, BD and LM revised the manuscript. ŽD supervised the research. All authors read and approved the final manuscript.

  2. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

  3. Employment or leadership: None declared.

  4. Honorarium: ZD has received honorariums from Shimadzu and ChromSystems. LM has received speaker honorariums from Berlin-Chemie, Servier Pharma, Boehringer Ingelheim, Bayer Pharmacy. SD, SB, SM, MS, BD, MM, VS and VB declare receiving no relevant honorariums.

  5. Competing interests: None declared.

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Received: 2017-12-12
Accepted: 2018-03-02
Published Online: 2018-04-12
Published in Print: 2018-07-26

©2018 Walter de Gruyter GmbH, Berlin/Boston

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