Low transthyretin is associated with the poor prognosis of colorectal cancer

Abstract

Objective: To determine whether transthyretin (TTR) influences the prognosis of patients with colorectal cancers and establish a predictive model based on TTR.

Methods: Between January 2013 and February 2019, the clinical data of 1322 CRC patients aged from 18 years to 80 years who underwent surgical treatment were retrospectively analyzed. The preoperative TTR level, clinicopathological data, and follow-up data were recorded. The X-tile program was used to determine the optimal cut-off value. Cox proportional hazard regression analysis was conducted to evaluate the correlation between the TTR and the cumulative incidence of cancer-specific survival (CSS). Nomograms were then developed to predict CSS. Furthermore, an additional cohort of 377 CRC patients enrolled between January 2014 and December 2015 was included as an external validation.

Results: Based on the optimal cut-off value of 121.3 mg/L, we divided the patients into the TTR-lower group (<121.3 mg/L) and the TTR-higher group (≥121.3 mg/L). Comparative analysis revealed that the TTR-higher group exhibited a younger demographic, a higher prevalence of low colorectal cancers, an elevated R0 resection rate, superior differentiation, earlier stage and lower levels of carcinoembryonic antigen (CEA) in contrast to the TTR-lower group. The Cox multivariable analysis underscored the significance of TTR and various clinicopathological factors, encompassing age, tumor location, R0 resection status, differentiation grade, disease stage, postoperative chemoradiotherapy, and preoperative CEA levels, as substantial prognostic indicators. The postoperative survival nomogram, when internally and externally assessed, demonstrated commendable performance across multiple metrics, including the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Compared with other models, the proportional hazards model combined with TTR demonstrates superior performance in terms of C-index, AUC, calibration chart, and DCA within the prognostic column chart.

Conclusions: The preoperative TTR was identified as a prognostic factor for predicting the long-term prognosis of CRC patients who underwent surgical treatment, supporting its role as a prognostic biomarker in clinical practice.

Keywords: cancer-specific survival; clinicopathologic feature; colorectal cancer; nomogram; prognosis; transthyretin.

Figure 1

The flowchart of the study.

Figure 2

Analysis of the optimal cut-off value of TTR by X-tile software. (A) An X-tile plot of TTR; (B) The optimal cut-off value was highlighted by a histogram. The optimal cut-off value for TTR was 121.3 mg/L.

Figure 3

Overall survival curve (A) and cancer-specific survival curve (B) for different TTR levels in CRC patients underwent surgical treatment.

Figure 4

Kaplan–Meier survival analysis of colorectal cancer patients who underwent surgery. (A) The overall survival of CRC patients aged ≤60 years; (B) The cancer-specific survival of CRC patients aged ≤60 years; (C) The overall survival of CRC patients aged >60 years; (D) The cancer-specific survival of CRC patients aged >60 years; (E) The overall survival of male CRC patients; (F) The cancer-specific survival of male CRC patients; (G) The overall survival of female CRC patients; (H) The cancer-specific survival of female CRC patients.

Figure 5

Univariate analysis of cancer-specific survival showed that TTR and other clinicopathological parameters were significant prognostic factors.

Figure 6

Multivariate analysis of prognostic factors with cancer-specific survival in 1322 CRC patients underwent surgical treatment.

Figure 7

A Cox proportional hazards Model A of cancer specific mortality for CRC patients underwent surgical treatment. (A) The nomogram of Model A. (B) 1-, 3-, and 5-year ROC comparison of Model A. (C) 1-, 3-, and 5-year calibration curves of Model A.

Figure 8

(A) Nomogram Model B and (B) Nomogram Model C.