Thromboelastography (TEG) parameters as potential predictors of malignancy and tumor progression in colorectal cancer

To accurately reflect the effect of colorectal tumor on TEG parameters, we applied a detailed data screening. A total of 142 participants were excluded from the data screening for the following reasons: Having other types of malignancies (n = 10), having rheumatic immune disease (n = 5), taking anticoagulants or anti-inflammatory drugs (n = 10), acute bleeding or obstruction (n = 7), transfusion (n = 11), infection (n = 15), preoperative adjuvant chemotherapy or radiotherapy (n = 17); no chance for surgery resection (n = 30), and TEG data are not available (n = 37). Finally, 115 HC, 43 patients with BA, and 387 patients with CRC were included after data exclusion. The primary demographic and clinical characteristics of the included participants were shown in Table 1. In brief, when compared with the HC group, the CRC group had higher levels of age, male ratio, smoking/drinking rate, PT, fibrinogen, D-dimer, CEA, and CA19-9 (P < 0.05). However, lower levels of hemoglobin and APTT were observed in the CRC group compared with the HC group (P < 0.05). In comparison with the BA group, the CRC group also manifested lower hemoglobin, higher platelet, higher fibrinogen, and higher CEA (P < 0.05). The significant difference between the HC group and the BA group was only displayed in hemoglobin and D-dimer (P < 0.05).

Table 1 Characteristics of healthy controls (HC), benign adenoma (BA) patients, and colorectal cancer (CRC) patients

Among the HC, BA, and CRC groups, all the TEG parameters (R, K, α-angle, and MA) reached statistical significance (Kruskal–Wallis, P < 0.05, Table 1). When compared in pairs, however, there was no statistical significance of TEG parameters between HC and BA groups after Bonferroni correction. The data showed that significant differences in TEG parameters still survived in the CRC group compared with the HC and BA groups, with shortened K, and higher α-angle/MA in the CRC group compared with the BA group (post hoc analysis, CRC vs. BA, P < 0.001, Table 1), and with shortened R/K, higher α-angle/MA in the CRC group compared with the HC group (post hoc analysis, CRC vs. HC, P < 0.05, Table 1). To eliminate the bias of confounding factors, we conducted PSM between HC + BA and CRC groups with a matching tolerance of 0.02. After PSM, we found that the TEG parameters had a moderate discriminative value in the identification of CRC from HC + BA. Among them, the AUC of K, α-angle, and MA were 0.693, 0.687, and 0.700, respectively. However, it is important to note that TEG parameters did not prove to be superior to traditional laboratory indicators in diagnosing CRC (Figs. 1 and 2, Table 2).

Fig. 1figure 1Fig. 2figure 2

ROC curve analysis of TEG parameters and laboratory parameters for distinguishing CRC from HC + BA (after propensity score matching). A TEG parameters. B Laboratory parameters

Table 2 The optimal cut-off values, sensitivity, specificity, PPV, NPV, and AUC for TEG parameters and laboratory parameters (distinguish CRC from HC + BA after propensity score matching)

Next, we tested the association between TEG parameters and clinical parameters of CRC patients. We observed that R had no significant effect on the clinical parameters of CRC patients (P > 0.05, Table 3). Notably, abnormal TEG parameters, including low K (LK), high α-angle (Hα), and high MA (HMA), were strongly associated with advanced tumors. Concretely, LK was significantly associated with vascular invasion (P = 0.001), primary tumor status (P = 0.002), lymph node metastasis (P < 0.001), and disease stages (P = 0.001); Hα was significantly associated with poorly differentiation (P = 0.002), vascular invasion (P < 0.001), nerve invasion (P = 0.029), primary tumor status (P < 0.001), lymph node metastasis (P < 0.001), and disease stages (P < 0.001); and HMA was significantly associated with poorly differentiation (P = 0.002), vascular invasion (P = 0.001), nerve invasion (P = 0.006), primary tumor status (P < 0.001), lymph node metastasis (P < 0.001), and disease stages (P < 0.001) (Table 3). In addition, patients with abnormal CEA/CA19-9 also showed a higher proportion of low K (LK), high α-angle (Hα), and high MA (HMA) compared with patients with normal CEA/CA19-9 levels (P < 0.05, Table 2). Patients with colon cancer displayed a higher proportion of LK, Hα, and HMA than patients with rectum cancer (P < 0.05, Table 3). Moreover, the females were associated with Hα and HMA (P < 0.05, Table 3).

Table 3 Association of TEG parameters with clinical parameters in patients with CRC

Further, we analyzed the relationship between TEG parameters and the TNM staging system. The Jonckheere-Terpstra test showed that K, α-angle, and MA were statistically significant for ordered difference (single increasing or decreasing) in primary tumor status (T1 → T2 → T3 → T4, P < 0.001, Fig. 3), lymph node status (N0 → N1 → N2, P < 0.001, Fig. 3), and disease stages (I → II → III → IV, P < 0.001, Fig. 3). In addition, statistics for pairwise comparisons (Kruskal–Wallis test and adjusted by Bonferroni correction) within groups were also shown in Fig. 3, showing that the more the tumor stage progressed, the more the TEG parameters were highly coagulated. Additionally, it should be highlighted that the sensitivity of K- and α-angle values in predicting advanced colorectal cancer patients, as determined by the AUC test, demonstrated a slight improvement compared to that of conventional laboratory parameters (Fig. 4, Table 4).

Fig. 3figure 3

TEG parameters in CRC patients with different stages by TNM staging system. Data was described by box plot (median and 5th–95th percentile). Comparison of TEG parameters between A primary tumor status T1 (n = 50), T2 (n = 62), T3 (n = 110), and T4 (n = 164); B regional lymph node status N0 (n = 236), N1 (n = 103), and N2 (n = 47); C tumor metastasis status M0 (n = 345) and M1 (n = 41); and disease stages I (n = 104), II (n = 122), III (n = 119), and IV (n = 41) of CRC patients. P was tested by Jonckheere-Terpstra for an ordered difference in medians. *P was tested by the Kruskal–Wallis test and adjusted by Bonferroni correction for pairwise comparison. *Represents the P < 0.05. **Represents the P < 0.001

Fig. 4figure 4

ROC curve analysis of TEG parameters and laboratory parameters for distinguishing disease stages III/IV from I/II in CRC patients. A TEG parameters. B Laboratory parameters

Table 4 The optimal cut-off values, sensitivity, specificity, PPV, NPV, and AUC for TEG parameters and laboratory parameters (distinguish disease stages III/IV from I/II in CRC patients)

During the postoperative follow-up period, only 59 CRC patients were retested for TEG (during the 3 months to 6 months after tumor excision). Surprisingly, we found a significant increase in K [1.8 (1.5, 2.3) vs. 1.9 (1.6, 2.6), P = 0.007] and a significant decrease in α-angle [65.3 (59.0, 68.6) vs. 63.7 (56.6, 68.5), P = 0.001]/MA [61.0 (58.2, 66.0) VS. 58.9 (55.8, 61.3), P < 0.006] after tumor surgery compared to the preoperative level (paired-samples T-test, Fig. 5).

Fig. 5figure 5

Comparison of TEG parameters between pre-operation and post-operation of CRC patients. P was tested by paired-samples T-test

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