*3.4. GSEA According to HIP1R mRNA Expression*

We performed GSEA to identify gene sets associated with HIP1R mRNA expression in the TCGA mRNA data of lung adenocarcinoma and lung squamous cell carcinoma cases. In lung adenocarcinoma, we identified the top 20 most prominent pathways that were upregulated in the low HIP1R mRNA expression group (Table S1). Four of the 20 were immune-related gene sets and were statistically significant (HALLMARK\_ALLOGRAFT\_REJECTION, HALLMARK\_INFLAMMATORY\_RESPONSE, HALLMARK\_IL6\_JAK\_STAT3\_SIGNALING, and HALLMARK\_IL2\_STAT5\_SIGNALING) (Figure 4). HALLMARK\_INTERFERON\_GAMMA\_RESPONSE is also upregulated in the low HIP1R mRNA expression group, although the statistical significance was marginal (*p* = 0.063). Core enrichment gene lists for HALLMARK\_ALLOGRAFT\_REJECTION, HALLMARK\_INFLAMMATORY\_RESPONSE, HALLMARK\_IL6\_JAK\_STAT3\_SIGNALING and HALLMARK\_IL2\_STAT5\_SIGNALING are summarized in Tables S2–S5. In lung squamous cell carcinoma, there were no statistically significant immune-related gene sets associated with HIP1R mRNA expression (Table S6).

**Figure 4.** Gene set enrichment analysis (GSEA) according to HIP1R mRNA expression. (**A**) HALL MARK\_ALLOGRAFT\_REJECTION pathway; (**B**) HALLMARK\_INFLAMMATORY\_RESPONSE pathway; (**C**) HALLMARK\_IL6\_JAK\_STAT3\_SIGNALING pathway; (**D**) HALLMARK \_IL2\_STAT5\_SIGNALING pathway.
