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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Prognostic value of glycated hemoglobin in colorectal cancer
Patrizia Ferroni, Vincenzo Formica, David Della-Morte, Jessica Lucchetti, Antonella Spila, Roberta D'Alessandro, Silvia Riondino, Fiorella Guadagni, Mario Roselli
Patrizia Ferroni, Fiorella Guadagni, San Raffaele Roma Open University, 00166 Rome, Italy
Patrizia Ferroni, David Della-Morte, Antonella Spila, Silvia Riondino, Fiorella Guadagni, Roberta D’Alessandro, Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele Pisana, 00166 Rome, Italy
Vincenzo Formica, Jessica Lucchetti, Silvia Riondino, Mario Roselli, Department of Systems Medicine, Medical Oncology Unit, Tor Vergata Clinical Center, University of Rome Tor Vergata, 00133 Rome, Italy
David Della-Morte, Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy
Author contributions: Ferroni P and Roselli M designed the study, analyzed the data and wrote the paper; Formica V, Della-Morte D and Lucchetti J enrolled the patients and collected clinical data; Spila A, D’Alessandro R and Riondino S performed the assays and collected laboratory data; Guadagni F designed the study, and revised the paper; all authors have read and approved the final version to be published; Guadagni F and Roselli M are co-senior authors for equal contribution.
Supported by European Social Fund, under the Italian Ministry of Education, University and Research, PON03PE_00146_1/10 BIBIOFAR (CUP B88F12000730005 to Guadagni F, partially).
Institutional review board statement: The study was reviewed and approved by the Scientific Institute for Research, Hospitalization and Health Care San Raffaele Pisana and by the Tor Vergata University Institutional Review Boards.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Patrizia Ferroni, MD, PhD, San Raffaele Roma Open University, IRCCS San Raffaele Pisana, Via di Val Cannuta 247, 00166 Rome, Italy. patrizia.ferroni@sanraffaele.it
Telephone: +39-06-52253733 Fax: +39-06-52255668
Received: September 10, 2016
Peer-review started: September 12, 2016
First decision: October 11, 2016
Revised: October 18, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: December 7, 2016
AIM
To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer (CRC) patients.
METHODS
Pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment (HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile. Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free (PFS) and overall survival (OS) was prospectively evaluated.
RESULTS
Fasting blood glucose, insulin, HOMA-IR and HbA1c (all P < 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage (P = 0.018) was an independent predictor of increased HbA1c levels, which were also higher in patients who had disease progression compared with those who did not (P = 0.05). Elevated HbA1c levels showed a negative prognostic value both in terms of PFS (HR = 1.24) and OS (HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients.
CONCLUSION
HbA1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes.
Core tip: The clinical significance of routinely used pre-treatment fasting blood glucose, insulin, HbA1c and homeostasis model of risk assessment was investigated in a cohort of colorectal cancer (CRC) patients. Despite all four metabolic markers were elevated in non-diabetic CRC patients, only elevated HbA1c levels were significantly associated with advanced CRC stage and disease progression, showing a negative prognostic value both in terms of progression-free (HR = 1.24) and overall (HR = 1.36) survival after adjustment for major confounders. These results suggest that glycemic metabolic markers, mainly HbA1c, should be carefully monitored in CRC patients as they could provide important risk stratification information.
