Serum tumor markers: Can they clinically implicate in type 2 diabetes mellitus?

Abstract

“Serum tumor markers expression (CA19-9, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus” authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus (T2DM). The study explores the diagnostic accuracy of tumor markers, particularly cancer antigen 19-9 (CA19-9), CA242, and carcinoembryonic antigen, in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%, employing receiver operating characteristic curve analysis. Though study offers valuable insights into the potential utility of tumor markers in clinical practice, caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost. Additionally, the study overlooks potential confounding factors like smoking and alcohol consumption. Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases, warranting further investigation into their diagnostic and prognostic implications. While Meng and Shi represent a significant contribution to the field, more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Key Words: Cancer antigen 19-9; Cancer antigen 242; Carcinoembryonic antigen; Tumor markers; Type 2 diabetes mellitus

Core Tip: The study explores the correlation between tumor markers and type 2 diabetes mellitus (T2DM), focusing on cancer antigen 19-9, cancer antigen 242, and carcinoembryonic antigen, in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%. While offering insights into their diagnostic accuracy, caution is advised against routine tumor marker testing due to challenges like availability and cost, and confounding factors like smoking and alcohol consumption. Meng and Shi’s study is significant, but further research is needed to clarify the role of tumor markers in diabetes management and beyond.

TO THE EDITOR

We read with great interest a recently published article entitled “Serum tumor markers expression (CA19-9, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus” authored by Meng and Shi[1] published in the World Journal of Diabetes. We wish to express our heartfelt gratitude to the authors for their invaluable contribution through the publication of this observational case-control study in your esteemed journal. The study explores the expression of tumor markers such as cancer antigen 19-9 (CA19-9), CA242, carcinoembryonic antigen (CEA) in type 2 diabetes mellitus (T2DM) and their clinical implications. We appreciate the investigators for correlating tumor markers with hemoglobin A1c (HbA1c). The authors’ use of receiver operating characteristic curve analysis to evaluate the diagnostic accuracy of tumor markers in patients with poorly controlled T2DM, particularly those with HbA1c levels exceeding 9%, is commendable. This approach not only adds depth to their research but also provides valuable insights into the potential utility of these markers in clinical practice. Furthermore, the inclusion of a substantial number of cases (82) compared to controls (51) enhances the robustness and confidence of the study findings. This balanced approach to sample selection lends credibility to the conclusions drawn and suggests a strong motivation to further explore this research area.

CEA is associated with both malignant and non-malignant conditions, including alcoholic, chronic liver failure, obstructive jaundice and smoking. Smoking can increase CEA levels with normal levels being ≤ 0.3 micrograms per litre and slightly higher levels < 5 micrograms per litre for smokers. Although CEA is cost effective, it has a major drawback due to its low sensitivity[2]. The study under review seems to overlook the potential confounding effects of smoking and alcohol consumption.

The levels of CA19-9 have been observed to be influenced by genotypic variations, particularly in instances where CA19-9 elevation occurs without a clearly attributable pathological condition[3]. Notably, within a cohort of 502 subjects undergoing health screening, 218 individuals exhibited heightened CA19-9 levels without a discernible underlying etiology, with recorded elevations spanning a range from 112 to 1338 U/mL[4,5]. It is important to acknowledge that CA19-9 elevation can occur in benign conditions; thus, caution is warranted in its utilization, particularly in asymptomatic patients, and its role as a screening tool is not endorsed[6]. Moreover, within the context of the present investigation, a statistically significant elevation in tumor markers such as CEA and CA19-9 has been delineated, further emphasizing the relevance of comprehensive tumor marker profiling in diagnostic assessments.

Variations in CA242 expression across diverse gynecological conditions, from benign to neoplastic entities such as uterine polyps and endometrial hyperplasia, highlight the multifaceted nature of this biomarker’s involvement in pathophysiological processes[7]. The heterogeneous pattern observed underscores the intricate interplay between CA242 and the underlying disease milieu, suggesting its potential utility in elucidating disease etiology and progression within the gynecological domain. This divergence in expression also hints at CA242’s broader role as a marker of systemic homeostasis, where deviations may indicate underlying systemic dysregulation. Moreover, the inverse correlation between CA242 levels and certain systemic conditions, including brain injury sequelae and anemia, elucidates the biomarker’s systemic implications beyond gynecological pathology. Emerging evidence linking CA242 levels with T2DM and coronary heart disease, as indicated by log10 P-values, supports its potential as a biomarker for systemic malfunction[8]. These observed associations suggest potential mechanistic links between CA242 dysregulation and the pathophysiology of these systemic diseases, warranting further investigation into its diagnostic and prognostic implications beyond gynecological contexts.

Meng and Shi’s study undoubtedly contributes significantly to the field, illuminating the fascinating intersection between tumor markers and diabetes management. However, given the studies discussed advocating for larger sample sizes, and potential challenges such as limited availability and high cost associated with these investigations, it is not advisable to recommend routine tumor marker testing for all cases of T2DM based solely on the current strength of evidence.

In essence, the wide range of conditions influencing CA242 expression, along with its associations with systemic diseases, highlights the need for a thorough exploration of its diagnostic and prognostic utility. Continued research efforts in this area hold the potential for harnessing CA242 as a valuable tool in elucidating both gynecological and systemic pathophysiology, thereby advancing clinical management strategies and improving patient outcomes.