Plasma IL‐6 and TNF‐α levels correlate significantly with grading changes in localized prostate cancer

Abstract

Purpose To study the effect of inflammatory markers in blood such as interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α) on the Gleason score (GS) changes in patients with prostate cancer (PCa) after radical prostatectomy (RP), we conducted this study. Patients and methods From November 2012 to September 2021, a total of 237 patients underwent RP at our institution. Blood samples from all patients were collected within 1 week before surgery. Preoperative clinical characteristics include age, serum IL‐6 and TNF‐α, neutrophil‐to‐lymphocyte ratio, C‐reactive protein, the platelet‐to‐lymphocyte ratio, lymphocyte‐to‐monocyte ratio, systemic immune‐inflammation index, the prostate imaging reporting and data system (PI‐RADS) score, prostate‐specific antigen, and biopsy GS were assessed. Univariate and multivariate logistic regression analyzes were used to determine the risk factors of GS changes after RP. The efficiency of this prediction model was identified with the area under the curve of the receiver operating characteristic curve. Results Seventy‐three patients (30.8%) had GS upgraded in the overall cohort, and 55 patients (23.2%) had GS downgraded. In comparing PCa patients with and without GS upgraded, multivariate logistic regression analysis showed that serum TNF‐α (odds ratio [OR]: 2.518, p = 0.019) and IL‐6 (OR: 0.478, p = 0.023) were independent factors predicting the occurrence of GS upgrade. We also compared the characteristics of patients with GS upgraded and GS downgraded; multivariate logistic regression analysis also demonstrated significant differences in serum IL‐6 and TNF‐α between these two groups (all p < 0.05). In addition, we found that low prostate volume and biopsy GS ≥ 7 were significantly associated with higher PI‐RADS sores in multivariate analysis. Conclusion The high expression of serum TNF‐α level is positively correlated with GS upgraded in PCa patients. High expression of serum IL‐6 level is negatively correlated with GS upgraded in PCa patients and positively related with GS downgraded.

The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors

“…In a study performed on 74 PCa patients, Nakashima et al [47] found that serum IL-6 significantly correlated with the clinical stage of PCa, as recently confirmed by Zhou et al [48] in a study showing that plasma IL-6 and TNFα levels significantly correlate with grading changes in localized PCa. IL-6R signaling has been demonstrated to be crucial in favoring the neuroendocrine differentiation in PCa, by the canonical activation of STAT3 transcription factor (Figure 1B) [49].…”

Frequency of ISUP 2014 Grade Group Upgrading in Radical Prostatectomy Patients and Associated Risk Factors: A Retrospective Study and Multivariate Analysis

“…Independent predictors of pathology grade upgrading identified in different studies may be listed as non-white race, older age, higher PSA levels, cancer positive biopsy fraction, prostate volume, prostate density and tumor percentage of >50% per core [18][19][20][21][22][23]. In a recent study, cancer upgrade has been shown to have a positive correlation with increased levels of TNF-alpha and a negative correlation with high levels of IL-6 (24). In an article by Epstein al., GS upgrading from <6 to a higher grade happened in 36.3% of 7643 cases [4].…”

Improving Whole Tomato Transformation for Prostate Health: Benign Prostate Hypertrophy as an Exploratory Model

“…In these mice, the FSMP diet significantly increased overall survival ( p < 0.01), delayed progression from prostatic intraepithelial neoplasia to adenocarcinoma, and decreased the incidence of poorly differentiated cancer. Biochemical studies disclosed a decrease in antioxidant activity in animal sera and a reduction in the circulating biomarkers of relevance to prostate carcinogenesis, such as IL-6 and TNF-α, which significantly correlated with PCa grade [ 116 ] and VEGF, known to be associated with prostate tumor grade, metastasis, and prognosis [ 117 ]. Indeed, the IL-6/STAT axis represents a link between inflammation and prostate carcinogenesis [ 105 ], which is the signal transducer and activator of transcription 3 (STAT3), a key modulator in the expression of a wide range of oncogenic genes [ 118 ] and a player in prostate cancer energy [ 119 ].…”