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S6. Relative abundance of CM and CMM gene pairs across tumor types.

S1. The tumor purity of immune-related genes. S2.

Table S1. Top 10 significant molecular terms (MSigDB c2cp; Curated Pathways) enriched in correlated and inversely-anticorrelated genes with tumor purity. Table S2. The GSEA results from individual tumor types. Table S3. Immune cell type-specific genes. Table S4. GSEA of genes with high/low differential correlation coefficients.

S3. Correlation between gene expression and tumor purity estimated across 21 tumor types.

S7. The frequency of PPI gene pairs across tumor types.

Surgical archives of tumor specimens are often impure. The presence of RNA transcripts from nontumor cells, such as immune and stromal cells, can impede analyses of cancer expression profiles. To systematically analyze the impact of tumor purity, the gene expression profiles and tumor purities were obtained for 7,794 tumor specimens across 21 tumor types (available in The Cancer Genome Atlas consortium). First, we observed that genes with roles in immunity and oxidative phosphorylation were significantly inversely correlated and correlated with the tumor purity, respectively. The expression of genes implicated in immunotherapy and specific immune cell genes, along with the abundance of immune cell infiltrates, was substantially inversely correlated with tumor purity. This relationship may explain the correlation between immune gene expression and mutation burden, highlighting the need to account for tumor purity in the evaluation of expression markers obtained from bulk tumor transcriptome data. Second, examination of cluster membership of gene pairs, with or without controlling for tumor purity, revealed that tumor purity may have a substantial impact on gene clustering across tumor types. Third, feature genes for molecular taxonomy were analyzed for correlation with tumor purity, and for some tumor types, feature genes representing the mesenchymal and classical subtypes were inversely correlated and correlated with tumor purity, respectively. Our findings indicate that tumor purity is an important confounder in evaluating the correlation between gene expression and clinicopathologic features such as mutation burden, as well as gene clustering and molecular taxonomy. Cancer Immunol Res; 6(1); 87–97. ©2017 AACR.

S4. Relationship with the tumor purity, CYT expression and neoantigen abundance.

Surgical archives of tumor specimens are often impure. The presence of RNA transcripts from nontumor cells, such as immune and stromal cells, can impede analyses of cancer expression profiles. To systematically analyze the impact of tumor purity, the gene expression profiles and tumor purities were obtained for 7,794 tumor specimens across 21 tumor types (available in The Cancer Genome Atlas consortium). First, we observed that genes with roles in immunity and oxidative phosphorylation were significantly inversely correlated and correlated with the tumor purity, respectively. The expression of genes implicated in immunotherapy and specific immune cell genes, along with the abundance of immune cell infiltrates, was substantially inversely correlated with tumor purity. This relationship may explain the correlation between immune gene expression and mutation burden, highlighting the need to account for tumor purity in the evaluation of expression markers obtained from bulk tumor transcriptome data. Second, examination of cluster membership of gene pairs, with or without controlling for tumor purity, revealed that tumor purity may have a substantial impact on gene clustering across tumor types. Third, feature genes for molecular taxonomy were analyzed for correlation with tumor purity, and for some tumor types, feature genes representing the mesenchymal and classical subtypes were inversely correlated and correlated with tumor purity, respectively. Our findings indicate that tumor purity is an important confounder in evaluating the correlation between gene expression and clinicopathologic features such as mutation burden, as well as gene clustering and molecular taxonomy. Cancer Immunol Res; 6(1); 87–97. ©2017 AACR.

Background : Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis and clinical outcomes in a variety of human malignancies. We investigated Cav-1 in primary and metastatic tumor of gastric cancer (GC) and its association with clinical outcomes. Method : All specimens evaluated were obtained from 145 patients with GC who had undergone curative gastrectomy. The primary outcomes measured were the expression levels of Cav-1 by immunohistochemistry and its association with clinicopathologicalparameters and patient survival. Results : Among the 145 patients, the frequency of high expression of stromal Cav-1 within primary tumor and tumoral Cav-1 protein in metastatic lymph node were 22.5% (18/145) and 16.6% (15/91). In the multivariate analysis tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882-8.224; P Conclusions : High expression of tumoral Cav-1 protein in metastatic lymph node shows a strong negative association with the clinical outcomes in patients with curatively resected GC, suggesting that this protein have potential uses as novel prognostic markers. Citation Format: Jihyung Hong, Der Sheng Sun, Soon Auck Hong, Hye Sung Won, Han Hong Lee, Okran Kim, Yoon Ho Ko. Prognostic value of metastatic tumoral caveolin-1 expression in patients with resected gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 301. doi:10.1158/1538-7445.AM2017-301

Gastric cancers expressing the stem cell marker CD133 are more aggressive than those that do not express the marker, and are associated with more unfavorable clinical outcomes. The CD133-associated aggressive behavior of gastric cancer remains poorly understood at the molecular level. In the present study, we performed gene expression profiling of bead-sorted CD133+ and CD133- KATO III cell lines to derive in vitro molecular signatures of CD133 expression in gastric cancer. Three expression signatures associated with CD133 expression ('Mitochondria', 'Cell cycle', and 'Lipid metabolism') were inferred upon study of a module association map of the key molecular signatures associated with CD133 expression in gastric cancer. Using the public gene expression profiles, we show that the patients with overexpression of CD133 show unfavorable clinical outcomes compared to CD133- patients in the context of up-regulation of 'Mitochondria' expression signature. We further showed that CD133+ KATO III cells had a higher mitochondrial function and were more susceptible to the mitochondrial inhibitors rotenone, antimycin A, and NaN3, than were CD133- cells. Together, our findings suggest that transcriptional up-regulation of the 'Mitochondria' gene signature may identify CD133+ gastric cancers; such data are of clinical and pharmacological relevance. Note: This abstract was not presented at the meeting. Citation Format: Han Hong Lee, Yoon Ho Ko, Tae-Min Kim, Won-Sang Park. Transcriptome analysis reveals mitochondrial gene signature upregulation in gastric cancers expressing the stem cell marker CD133 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3883. doi:10.1158/1538-7445.AM2017-3883

Background: Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and progression of human cancers. The aim of this study was to investigate the expression of autophagy-related proteins in colorectal cancer (CRC), and to evaluate their prognostic significance. Methods: We analyzed the expression of 3 autophagy-related proteins (LC3B, beclin-1, ATG5) in 263 resected colorectal cancer specimens by immunohistochemistry using tissue microarray. Results: Of the 263 patients, autophagy-related protein expression frequencies were 71.3% (174/244) for beclin-1, 74.7% (186/249) for LC3B, and 65.1% (151/232) for Atg5. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Kaplan-Meier analysis showed that low LC3B expression was positively linked to poor prognosis of the patients with CRC. Cox's proportional hazard model demonstrated that curative resection status, lymph node metastasis, LC3B expression, and the alteration of autophagy-related proteins were independent prognostic factor for CRC. Conclusion: Alterations in the expression of autophagy-related proteins are closely associated with prognosis of CRC, suggesting that expression patterns may be used as a prognostic marker. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B17. Citation Format: Han Hong Lee, Ji Hye Choi, Young-Seok Choi, Yoon Ho Ko. Decreased expressions in autophagy-related proteins is associated with poor prognosis in patients with colorectal adenocarcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B17.