C-Reactive Protein and Platelet-Lymphocyte Ratio as Potential Tumor Markers in Low-Alpha-Fetoprotein Hepatocellular Carcinoma

Abstract

The hepatocellular carcinoma (HCC) tumor marker alpha-fetoprotein (AFP) is only elevated in about half of the HCC patients, limiting its usefulness in following the effects of therapy or screening. New markers are needed. It has been previously noted that the inflammation markers C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR) are prognostically important and may reflect HCC aggressiveness. We therefore examined these 2 markers in a low-AFP HCC cohort and found that for HCCs > 2 cm, both markers significantly rise with an increasing maximum tumor diameter (MTD). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index value for each marker, and their area-under-the-curve values for each MTD group. Patients were dichotomized into 2 groups based on the CRP and PLR from the receiver-operating characteristic curve analysis. In the logistic regression models of the 4 different MTD patient groups, CRP and PLR levels were statistically significant to estimate MTD in univariate logistic regression models of MTD groups > 2 cm. CRP and PLR were then combined, and the combination was statistically significant to estimate MTD groups of 3-, 4-, and 5-cm cutoffs. CRP and PLR thus have potential as tumor markers for low-AFP HCC patients, and possibly for screening.

Diagnostic value of fibrinogen to prealbumin ratio and gamma-glutamyl transpeptidase to platelet ratio in the progression of AFP-negative hepatocellular carcinoma

“…Numerous inflammatory response markers have been presented as effective, economical, and reliable indicators for the diagnosis and prognosis of AFP-NHCC. These markers include PA [33], D-Dimer [33], C-reactive protein [34], platelet-lymphocyte ratio [34], lactate dehydrogenase [35] and GGT [35]. However, the predictive roles of FPR and GPR in AFP-NHCC remained unknown.…”

Serum levels of inflammatory markers CRP, ESR and albumin in relation to survival for patients with hepatocellular carcinoma

“…Inflammation, both local (CRP) and systemic (ESR) has recently emerged as an important reflection of HCC aggressiveness and prognosticator. Various other clinical approaches have been taken to its measurement, including peripheral blood neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios 21,33‐49 . These novel markers of disease activity are especially needed for that 50% of HCC patients who do not have elevated AFP levels 30,46,50 .…”

“…Various other clinical approaches have been taken to its measurement, including peripheral blood neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios. 21,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] These novel markers of disease activity are especially needed for that 50% of HCC patients who do not have elevated AFP levels. 30,46,50 However, a central unanswered question is why elevated values of these inflammation markers predict poor survival.…”

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

“…The scores based on platelets were tested in several forms of cancer, and results are encouraging for their use as possible biomarker in clinical practice [105,106,107]. In this regard, the platelet-to-lymphocytes ratio (PLR) combined with C-reactive protein was demonstrated to be a reliable marker for small HCCs in patients with low serum AFP levels, with increasing PLR values associated with larger tumors [108,109]. Moreover, elevated PLR values were associated with poor prognosis in patients with HCC.…”