Tissue MICA/B expression and serum soluble MICA in cholangiocarcinoma: Associations with survival and advanced disease.

Cholangiocarcinoma (CCA) has a poor prognosis, highlighting the need for clinically informative biomarkers. This retrospective study examined associations of major histocompatibility complex class I chain-related molecules A (MICA) and B (MICB) and serum soluble MICA (sMICA) with clinical characteristics and survival. Transcript levels, combined tissue MICA and MICB (MICA/B) protein expression, and serum sMICA were assessed using real-time reverse transcription polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay in partially overlapping cohorts of 30, 101, and 118 patients, respectively; serum from 10 controls was also analyzed. Survival associations were evaluated using Kaplan-Meier and Cox regression analyses. MICA transcript levels were elevated in tumors compared with paired adjacent normal tissues (p = 0.006), whereas MICB transcripts were detected in 7/30 tumors. High tissue MICA/B expression was associated with longer median overall survival (40.70 versus 16.36 months; p = 0.008) and lower mortality after multivariable adjustment (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89; p = 0.020). Serum sMICA was elevated in advanced CCA. Exploratory analyses yielded areas under the receiver operating characteristic curve of 0.689 for advanced versus non-advanced CCA and 0.770 for advanced CCA versus controls. At an exploratory upper-quartile threshold (>1466.62 pg/mL), high sMICA was associated with shorter survival (p = 0.014), but the adjusted association was not statistically significant (hazard ratio, 1.89; 95% confidence interval, 0.93-3.84; p = 0.081). Tissue MICA/B expression may have prognostic relevance, whereas serum sMICA may reflect advanced disease; independent prospective validation is required.