A Bioinformatic Approach for the Identification of Molecular Determinants of Resistance/Sensitivity to Cancer Thermotherapy

Application of heat above 43°C and up to 47°C, the so-called “thermal ablation” range, leads to tumor cell destruction either by apoptosis or by necrosis. However, tumor cells have developed mechanisms of defense that render them thermoresistant. Of importance, the in situ application of heat for the treatment of localized solid tumors can also prime specific antitumor immunity. Herein, a bioinformatic approach was employed for the identification of molecular determinants implicated in thermoresistance and immunogenic cell death (ICD). To this end, both literature-derived (text mining) and microarray gene expression profile data were processed, followed by functional enrichment analysis. Two important functional gene modules were detected in hyperthermia resistance and ICD, the former including members of the heat shock protein (HSP) family of molecular chaperones and the latter including immune-related molecules, respectively. Of note, the molecules HSP90AA1 and HSPA4 were found common between thermoresistance and damage signaling molecules (damage-associated molecular patterns (DAMPs)) and ICD. In addition, the prognostic potential of HSP90AA1 and HSPA4 overexpression for cancer patients' overall survival was investigated. The results of this study could constitute the basis for the strategic development of more efficient and personalized therapeutic strategies against cancer by means of thermotherapy, by taking into consideration the genetic profile of each patient.