High intratumoral LC3 expression was associated with improved survival and low risk of tumor recurrence after surgical resection in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). According to the study’s authors, “LC3 can be considered an independent predictive factor of [disease-free survival] and [overall survival] in cHCC-CC patients.”

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Out of the 40 cHCC-CC patients included in the study, 33 had high and 7 had low intratumoral expression of LC3. Overall survival (OS) rates were significantly improved (hazard ratio: 6.74, 95% CI, 1.68‑26.9, P =.007) in patients with high LC3 expression, with a higher cumulative incidence of OS at 1-, 3-, and 5-year follow-up. For patients with high intratumoral LC3 expression, the 5-year OS rate was 61.2%, in contrast to the 0% observed for patients with low LC3 expression.

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Patients with high LC3 expression also had greater disease-free survival (DFS) rates (hazard ratio: 51.3, 95% CI, 2.85‑922, P =.008) than those with low LC3 expression. The cumulative incidence of DFS was higher at 1-, 3-, and 5-year follow-up, with a maximum difference registered at 5-year DFS rate (74.6% vs 0% for high and low LC3 patients, respectively).

High LC3 expression was associated with milder clinicopathological characteristics, including macrovascular invasion [1 (3.1%) vs 6 (85.8%), P <.001], lymph node metastasis [2 (6.1%) vs 5 (71.5%), P <.001], American Joint Committee On Cancer (AJCC) stage III [2 (6.1%) vs 5 (71.5%), P <.001], Barcelona Clinic Liver Cancer (BCLC) stage C [3 (9.1%) vs 4 (57.1%), P =.006], tumor recurrence [5 (15.2%) vs 5 (71.4%), P =0.001], and mortality [9 (27.2%) vs 6 (85.8%), P <.001].

The study authors also found tumor factors to be correlated with poor OS, including the presence of microvascular invasion (hazard ratio: 0.07, 95% CI, 0.01‑0.46, P =.006) and multiple tumors (hazard ratio: 0.03, 95% CI, 0.01‑0.34, P =.004). Cirrhosis was associated with improved (hazard ratio: 17.9, 95% CI, 1.05–306, P =.046) DFS.

The LC3 protein, also known as microtubule-associated protein 1A/1B-light chain 3, is an autophagy-related protein. Beclin-1 and p62, 2 additional key mediators of autophagy, were also found to be overexpressed in 62.5% and 76.5%, respectively, of the tumor specimens assessed in the present study.


Perng D-S, Hung C-M, Lin H-Y, et al. Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection. BMC Cancer. 2021;21(1):828. doi:10.1186/s12885-021-08553-6