Background: Liver function is a routine laboratory test prior to curative liver resection. It remains unclear whether the albumin-bilirubin (ALBI) grade and albumin-to-alkaline phosphatase ratio (AAPR) can predict long-term outcomes of surgically treated patients with intrahepatic cholangiocarcinoma (ICC). Methods: This study investigated the correlation between ALBI grade and AAPR with overall survival (OS) after liver resection and then compared their accuracy to the Child-Pugh score. Harrell's concordance index (C-index) and Akaike information criterion (AIC) were used to compare accuracy of models. Results: A total of 620 ICC patients were included, 477 in derivation cohort and 143 for validation. 0.348 was identified as the cutoff value for AAPR after calculating the Youden index. In the derivation cohort, elevated ALBI grade was associated with worse prognosis [hazard ratio (HR): 1.751, 95% confidence interval (CI): 1.329 to 2.306], and a decreased AAPR value was correlated with shorter OS (HR: 1.969, 95% CI: 1.552 to 2.497). Multivariate analysis suggested that the ALBI grade, AAPR, CA19-9, tumor number, and microvascular invasion were independent prognostic predictors for OS. ALBI grade and AAPR showed more accuracy in evaluating OS for surgically treated ICC patients than the Child-Pugh score (C-index: 0.559, 0.600 vs. 0.528; AIC: 3023.84, 3007.73 vs. 3034.66). Our findings were validated in an independent cohort from another clinical center. Conclusions: Importantly, the ALBI grade and AAPR showed greater discriminatory power than the Child-Pugh score in assessing long-term outcomes following hepatectomy for ICC. The AAPR was more accurate than the ALBI grade. It was beneficial to consider the ALBI grade and AAPR as useful surrogate markers to identify patients at risk of poor postoperative outcomes.

Long-term survival in oesophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. However, effective biomarkers to predict the pathologic response are still lacking. Therefore, a systematic analysis focusing on genes associated with the efficacy of chemoradiotherapy in ESCC will provide valuable insights into the regulation of molecular processes. By screening publications deposited in PubMed, we collected genes associated with the efficacy of chemoradiotherapy. A specific subnetwork was constructed using the Steiner minimum tree algorithm. Survival analysis in Kaplan-Meier Plotter online resources was performed to explore the relationship between gene mRNA expression and the prognosis of patients with ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical staining (IHC) were used to evaluate the expression of key genes in cell lines and human samples. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. Transwell assays assessed cell migration, and cell viability was detected using the Cytotoxicity Assay. Finally, we identified 101 genes associated with efficacy of chemoradiotherapy. Additionally, specific molecular networks included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1, and UGDH. The MMS22L mRNA expression level showed the most significant association with the ESCC patient outcome (p < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (p < 0.001) and protein levels in tumour tissues compared with that in normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (p < 0.01). MMS22L levels were inversely correlated with the NCRT response in ESCC (p < 0.01). The resulting area under the ROC curve was 0.847 (95% CI: 0.7232 to 0.9703; p < 0.01). In conclusion, low expression of MMS22L is associated with poor response to NCRT, worse survival, lymph node metastasis, and enhanced migration of tumour cells in ESCC.

The prognostic significance of tumor burden score (TBS) on patients who underwent curative-intent resection of intrahepatic cholangiocarcinoma (ICC) has not been evaluated. The present study aimed to investigate the impact of TBS and its synergistic effect with CA19-9 (combination of TBS and CA19-9, CTC grade) on long-term outcomes.