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.