Discussion
PSA is a glycoprotein, from the family of human kallikrein proteins and encoded by the KLK3 gene. PSA was approved by the FDA in 1986 and a high level of PSA together with positive findings of DRE have been strongly linked as diagnostic markers for PCa.12 Despite being organ-specific, PSA is not cancer-specific. PSA levels might be increased in some non-malignant diseases such as benign enlargement and prostatitis.13 Furthermore, much laboratory data, which could easily be obtained, has not shown PSA as having a predictive value in the diagnosis of PCa. Recently, prostate cancer antigen 3 (PCA 3), a urine-based assay, was approved by the FDA. PCA3 can prevent unnecessary prostate biopsies but predicting the presence of PCa still lacks clinical validation.13 The Mi-Prostate score (MiPS) screens for the presence of the PCA3 gene and an RNA biomarker has been found to be more specific than PSA alone, but it needs to be validated.14 Urokinase plasminogen activation (uPA and uPAR) is involved in PCa progression, however it seems to be helpful in predicting poor pathologic characteristics rather than diagnosis of PCa.15 There have also been a number of studies about the diagnostic role of the platelet-to-lymphocyte ratio (PLR)16-19; the neutrophil-to-lymphocyte ratio (NLR)20 and the combined use of PSA, mean platelet volume (MPV), and platelet distribution width (PDW).21These studies found these values to be associated with a poor prognosis in PCa patients.
In this study, we investigated a novel index, the HALP score, which consists of the hemoglobin, albumin, lymphocytes, and platelets levels, to predict PCa. As known, while hemoglobin and albumin levels are associated with the nutrition status of the body, lymphocytes and platelets are related to the immune system. This score system has been usually used to predict the prognosis of some types of cancers by using the character of showing the two main roles (inflammation and nutrition status) in the prognosis of cancer. Chen et al. firstly described this score system to predict the prognosis of gastric cancer.10 Then it was used in esophageal squamous cell carcinoma 22, renal cell carcinoma8, bladder cancer 9, prostate cancer7, lung cancer 23, colorectal cancer11 ,and pancreatic cancer 24 for predicingt the prognosis of the above-mentioned cancer types in the literature. Guo et al. showed that the HALP score was an independent prognostic factor for PSA-progression free survival in patients with metastatic PCa or oligometastatic PCa after cytoreductive radical prostatectomy. Guo et al. also reported that NLR and PLR had no statistically significant association and their predictive ability was lower than the HALP score.(7) However, there were no reports that the HALP score has any role in diagnosing any type of cancer.
In our study, the mean HALP scores of patients with BPH and PCa were 49.43 and 51.2 points, respectively. However, this difference was not statistically significance (p= 0.737). Guo et al. mentioned the importance of a low HALP score and its association with a poor clinical outcome. In comparison to their work, we found that the HALP scores were higher in Group 2. After observing the low diagnostic efficacy of the HALP score in prostate cancer, we examined each of the components of the scoring system to see if they would predict PCa separately.
There was no difference in hemoglobin or platelet levels between the two groups (Table 1). No significant difference in hemoglobin level between the groups was an expected result, because the PCa patients in our study were almost all in the early stage of cancer and cancer related anemia is associated with advanced stages of cancer, due to the chronic blood loss, iron deficiency, and vitamin B12 or folate nutritional deficiency.(8, 25) It was shown that natural killer cells attack the tumor cells to defend the vessels, but these tumor cells are protected from natural killer cells by platelets.22, 26 But, there was no difference between the two groups in our study in the hemoglobin levels, because the patients with PCa were in the early stages of cancer, so no tumor growth or metastasis would be evidence by high platelet levels.
Lymphocyte levels were higher in the PCa group, and this was statistically significant. Lymphocytes have a role on inhibiting the tumor cells proliferation, invasion, or metastasis8, 27 while a low level of lymphocytes is common in patients with advanced cancer. The main significant difference in the level of lymphocytes between the two groups in our study could be that the cancer was in an initial state and the immune system might be trying to defend against the tumor cells; so the level of lymphocytes were higher in group 2.
In our study the most interesting finding was the albumin level; this was significantly lower in the PCa group. The albumin level is accepted as the indicator of nutrition status and has been shown to be a valuable prognostic factor in cancer patients.23, 28 The nutrition status would not be affected at the beginning of the cancer, and the activation of the mechanism is due to the inflammatory mediators increasing the transcapillary escape. Another mechanism is IL-6, TNF and acute phase reactants may lead to decreased production of albumin.29 Sejima et al. suggested that preoperative hypoalbuminemia may lead to the spread of localized prostate cancer and be associated with biochemical recurrence.29 The ROC curve analysis in our study demonstrated a higher diagnostic efficacy of albumin to PSA, but this was not statistically significant. Albumin levels were statistically significant compared to platelet count and the HALP score, except PSA and lymphocyte as we mentioned above (Table 2). We believed that albumin levels are important in prostate cancer, as in many other cancers. Overall, the effect of testosterone on PCa is still unclear. We know that androgens can promote PCa in animal models and androgen deprivation therapy (ADT) is beneficial in PCa patients. However, after a large number of mostly retrospective studies, there remains no clear association with higher endogenous testosterone and the development or severity of PCa.(30) On the other hand, free testosterone may have an impact on PCa with its active effect on the synthesis of dihydrotestosterone in prostate tissue.29Serum albumin decrease reduces the level of albumin–binding testosterone and ultimately an increase in the level of free testosterone. This point may be the critical relationship between lower albumin levels and PCa. Sejima et al. also reported pre–operative low serum albumin levels as a predictor for biochemical recurrence and that lymph node metastasis may be related to increased free testosterone contributions.29
To our knowledge, this is the first study to assess the diagnostic value of HALP levels in patients with PCa. We acknowledge that there were some limitations in the present study. The retrospective design from single center, and the small number of patients are the main limitations.