In this retrospective study, we aimed to shed light on the potential prognostic significance of serum CHE levels within the context of HIV-related DLBCL. Our investigation revealed the following results: (a) HIV-related DLBCL patients with low serum CHE levels exhibited a higher incidence of anemia, hypoproteinemia and inflammatory indicators. (b) HIV-related DLBCL patients with low CHE levels were more frequently classified as having advanced IPI scores and Ann Arbor stage. (c) High baseline CHE levels were closely correlated with improved ORR and OS. Thus, baseline CHE levels hold promise as a valuable prognostic marker for HIV-related DLBCL patients.
"Clinical serum cholinesterase" typically refers to pseudocholinesterase, which is predominantly synthesized in hepatocytes[20]. Therefore, low levels of serum pseudocholinesterase are often used as an indicator of impaired hepatic synthetic capacity. Patients with malignancy often receive high-dose chemotherapy, experience weight loss and exhibit malnutrition, which can affect liver synthetic function, including CHE production. Serum CHE has been reported to be a prognostic factor in several solid cancers [8, 12].
We identified that CHE can serve as a reliable surrogate marker for predicting OS and ORR in HIV-related DLBCL patients. Specifically, patients with CHE ≤ 5500 U/L exhibited significantly poorer OS and ORR, even after adjustment for potential confounding factors. The associations between CHE and patient outcomes can be attributed to several reasons:
First, it is worth noting that nutrition has a profound impact on the outcomes of patients with HIV-related DLBCL. A high incidence of anemia and hypoalbuminemia among HIV-related DLBCL patients with low CHE levels was observed in our research. Serum albumin has been widely used as a diagnostic marker for malnutrition in clinical practice. Low serum albumin is associated with inferior outcomes in patients with DLBCL [21, 22]. The anemia probably results from DLBCL involvement of bone marrow and dietary causes [23, 24]. There is a life-saving requirement for higher nutritional intake for patients with anemia and hypoproteinemia. Of note, canonical correlation analysis confirmed that CHE had a robust correlation with nutrition-related indicators (total protein, albumin, hemoglobin and BMI) in our study. Importantly, a combined assessment of serum cholinesterase and albumin levels can serve as nutrition-related serum markers and be successfully employed to predict prognosis in cancer patients [11, 25]. In addition, cancer patients with poorer nutritional status are less likely to complete oncologic treatment according to plan and are at a high risk of developing adverse outcomes.
Second, persistent inflammation has been shown to have a detrimental effect on the outcomes of DLBCL patients. Elevated levels of CRP were observed in HIV-related DLBCL patients with lower CHE levels in our study. Inflammation plays a crucial role in various stages of tumor development, including initiation, growth, invasion, and metastasis. The presence of persistent inflammation creates an environment that facilitates tumor progression and contributes to the development of certain types of cancer [26]. Elevated CRP levels are frequently detected in individuals with cancer, particularly those with advanced or metastatic disease, which are related to poor prognosis [26, 27]. This is because tumors can trigger the release of inflammatory cytokines, which in turn stimulate the liver to produce more CRP [28]. In our research, we found a strong correlation between CRP and CHE, providing an explanation for why CHE levels can serve as a promising prognostic marker for DLBCL. Additionally, cell-based inflammation consisting of neutrophils and lymphocytes is also significantly associated with the progression of cancer and metastasis of malignant cells[29, 30]. In our study, the differences in neutrophils and lymphocytes between different ChE groups were not pronounced, possibly due to the impact of HIV itself on the destruction of lymphocytes and neutrophils.
Third, our study provided evidence of a significant association between low CHE levels and advanced stages of HIV-related DLBCL. Specifically, 92.6% of patients with CHE levels ≤ 5500 U/L were classified as Ann Arbor stage III/IV, and 85.2% of patients with CHE levels ≤ 5500 U/L had an IPI score > 3. These findings indicate that CHE is an indicator of DLBCL disease progression. The advanced stage of DLBCL deteriorates the prognosis of patients.
Compared to other factors for cancer prognosis, CHE has the advantage of being cost-effective and easy to implement, with less interference in clinical settings. In light of our research findings, we strongly recommend that serum CHE levels be used as a valuable prognostic marker for HIV-related DLBCL patients.
There are some limitations in our study. First, the sample size was relatively small, and consequently, a large cohort study is needed to further confirm our conclusions. Second, our study was a retrospective study conducted in a single medical center. A prospective study is needed to further elucidate our results. Third, the follow-up period was only one year, which may not have captured the long-term outcomes of patients.
In conclusion, our study findings provide strong evidence of a close relationship between serum CHE levels and nutrient status as well as inflammation in HIV-related DLBCL patients. Notably, patients with low serum CHE levels were found to be predominantly in advanced stages of the disease and exhibited poor ORR and 1-year OS. Based on our robust data, serum CHE levels show great potential as a surrogate marker for risk stratification and for guiding treatment decisions in patients with HIV-related DLBCL.