Cancer Res Treat.  2020 Apr;52(2):469-480. 10.4143/crt.2019.423.

An Integrated Nomogram Combining Clinical Factors andMicrotubule-Associated Protein 1 Light Chain 3B Expression to PredictPostoperative Prognosis in Patients with Intrahepatic Cholangiocarcinoma

Affiliations
  • 1Department of Hepatic Surgery and Liver Transplantation Center, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
  • 2Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou
  • 3Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China

Abstract

Purpose
Microtubule-associated protein 1 light chain 3B (LC3B) serves as a key component of autophagy, which is associated with the progression of carcinoma. Yet, it is still unclear whether LC3B is also an independent risk factor for intrahepatic cholangiocarcinoma (ICC). We aim to explore the predictive value of LC3B on prognosis of ICC, and to establish a novel and available nomogram to predict relapse-free survival (RFS) and overall survival (OS) for these patients after curative-intent hepatectomy.
Materials and Methods
From August 2004 to March 2017, 105 ICC patients were eligibly enrolled in the Third Affiliated Hospital of Sun Yat-sen University. Preoperative clinical information of enrolled patients was collected. Expression LC3B in the ICC specimen was detected by immunohistochemistry.
Results
The 5-year RFS and OS in this cohort were 15.7% and 29.6%, respectively. On multivariate Cox regression analysis, independent risk factors for 5-year OS were cancer antigen 125, microvascular invasion, LC3B expression and lymph node metastasis. Except for the above 4 factors, neutrophil/lymphocyte ratio and tumor differentiation were independent factors for 5-year RFS. The area under the curve of nomograms for OS and RFS were 0.820 and 0.747, respectively.
Conclusion
The nomograms based on LC3B can be considered as effective models to predict postoperative survival for ICC patients.

Keyword

Intrahepatic cholangiocarcinoma; Autophagy; LC3B; Nomogram; Prognosis

Figure

  • Fig. 1. Representative immunohistochemistry samples (×200) of low (A) and high (B) microtubule-associated protein 1 light chain 3B (LC3B) expression in intrahepatic cholangiocarcinoma patients and Kaplan-Meier analysis of overall survival (OS) (C) and relapse-free survival (RFS) (D) for patients with low and high expressed LC3B after surgery.

  • Fig. 2. The nomogram for predicting overall survival of intrahepatic cholangiocarcinoma patients after surgery. CA-125, cancer antigen 125; LC3B, microtubule-associated protein 1 light chain 3B; MVI, microvascular invasion; LNM, lymph node metastasis; OS, overall survival; RFS, relapse-free survival.

  • Fig. 3. The nomogram for predicting relapse-free survival of intrahepatic cholangiocarcinoma patients after surgery. CA125, cancer antigen 125; NLR, neutrophil-to-lymphocyte ratio; LNM, lymph node metastasis; MVI, microvascular invasion; LC3B, microtubule-associated protein 1 light chain 3B.

  • Fig. 4. The calibration curves for predicting patients’ postoperative survival. (A) 1-Year overall survival (OS). (B) 1-Year recurrence-free survival (RFS). (C) 3-Year OS. (D) 3-Year RFS. (E) 5-Year OS. (F) 5-Year RFS.

  • Fig. 5. Kaplan-Meier postoperative survival analysis of overall survival (OS) and relapse-free survival (RFS) according to TNM staging (A, B) and three risk groups stratified by individual total points of nomograms for intrahepatic cholangiocarcinoma patients (C, D) respectively.

  • Fig. 6. Sensitivities and specificities for the nomograms and other independent risk factors for postoperative survival of intrahepatic cholangiocarcinoma patients. (A) Area under the curve (AUC) was compared among the nomogram for overall survival (OS), cancer antigen 125 (CA-125), microtubule-associated protein 1 light chain 3B (LC3B), microvascular invasion (MVI), and lymph node metastasis (LNM). (B) AUC was compared among the nomogram for RFS, neutrophil-to-lymphocyte ratio (NLR), LC3B, tumor differentiation, LNM, MVI, and CA-125.


Reference

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