Association between CT-based adipose variables, preoperative blood biochemical indicators and pathological T stage of clear cell renal cell carcinoma

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification.

Methods: This retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables.

Results: In specific intervals, fibrinogen levels (FIB) (2.63-4.06 g/L) and platelet (PLT) counts (>200.34 × 10⁹/L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 10⁹/L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL).

Conclusion: Preoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning.

Keywords: Adipose tissue; Blood chemical indicator; Clear cell renal cell carcinoma (ccRCC); Computed tomography (CT); Pathological T stage.

Fig. 1

Overview of the design and patients' enrollment. ccRCC = clear cell renal cell carcinoma.

Fig. 2

The schematic representation of multidimensional imaging parameters. (A). Quantitative measurements of abdominal fat. A yellow line outlined the region of interest along the abdominal wall muscle group at the level of the umbilicus. The CT value range was set from −150 Hounsfield units (Hu) to −50 Hu. The red area represents the VFA, and the blue area represents the SFA. (B, C). The methods for measuring perinephric fat at the level of the renal vein. The abbreviation "L" stands for LPFT; "P" stands for PPFT, and "RV" represents the renal vein. d: Measurement of PFV. (D) Perirenal fat (yellow), normal renal tissue (red), and tumor (white) based on segmentation using the syngo via workstation. (E-G). Grading of PFS. (E). Type 0 (none) - 0 points. The fat surrounding the kidney shows no stranding, and the tissue appears completely black on the CT image. (F). Type 1 (mild/moderate) - 2 points. Some image-dense stranding is present in the fat around the kidney, but there are no thick bars of inflammation. (G). Type 2 (severe stranding) - 3 points. The CT image shows severe stranding around the kidney with thick, image-dense bars of inflammation. VFA = visceral fat area; SFA = subcutaneous fat area; LPFT = Lateral perinephric fat thickness; PPFT = Posterior perinephric fat thickness; PFS = Perinephric fat stranding; PFV = Perirenal fat volume; PFS = perinephric fat stranding; CT = Computed tomography.

Fig. 3

Nonlinearly correlated variables and their cut-off values/intervals with ccRCC T stage after adjusting for site, gender, age, BMI, and preoperative comorbidities. Preoperative biochemical parameters showing a significant positive correlation with ccRCC pathological T stage in the panel (A) PLT, (D) FIB, and (G) TAM. (B, C). Preoperative PLT counts. The plots illustrated the prevalence of T stage before and after the turning point (Log_e^PLT = 5.3, i.e., PLT = 200.34 × 10⁹/L). Before the turning point, the prevalence of high T stage (T3 and T4) was lower, but after the turning point, the prevalence of high T stage increased significantly. (E, F). Preoperative FIB levels. The plots shown indicated a positive correlation between elevated FIB levels and T stage, when the preoperative FIB level fell within the specified cut-off interval (0.967 < Log_e^FIB < 1.400, i.e., 2.63 g/L ≤ FIB <4.06 g/L). (H, I). Preoperative TAM level. The plots demonstrated that the increase in preoperative TAM level showed a positive correlation with T stage. This correlation holds true for TAM level both above the cut-off value (TAM >90.556 U/mL) and below the cut-off value (TAM <90.556 U/mL). Data in 3A and 3D are presented as median ± IQR, while data in 3G are presented as mean ± SD. Data for the remaining panels are presented as mean with SEM. ccRCC = clear cell renal cell carcinoma; PLT = platelet; TAM = tumor-associated material; FIB = fibrinogen; IQR = interquartile range; SD = standard deviation; SEM = standard error of the mean.