Abstract 3125: Analysis of intratumoral protein and gene expression heterogeneity in gastric cancer with a clustering analysis

Background/Aim: Intratumoral heterogeneity has been reported in various cancer types and may cause cancer metastasis and chemotherapy treatment resistance, including resistance to molecular targeted therapy. In gastric cancer, the intratumoral heterogeneity of cancer-associated molecules, such as HER2, has been reported and relates to the acquisition of chemotherapy resistance. To reveal whether intratumoral heterogeneity is related to cancer etiology, such as the mechanism of metastasis, and the development of new treatment strategies, such as combination therapy, we investigated intratumoral heterogeneity of gastric cancer with operative specimen and Cancer Genome Atlas (TGCA) data. Methods: The study included 503 patients who underwent gastrectomy and immunohistochemical staining for gastric cancer between 2001 and 2006 and TGCA data. We conducted clustering analysis based on protein and gene expression data for FGFR2IIIb (FGFR2), HER2(ERBB2), CXCR2(CXCR2), CXCR4(CXCR4), cMet(MET), TGFβ1(TGFB1), IGF1R(IGF1R), and p-smad2(SMAD2), and we analyzed the relation of FGFR2IIIb (FGFR2) and HER2(ERBB2) expression with the expression of other proteins and genes. Additionally, we investigated clinicopathological feature correlations. Result/Discussion: We divided gastric cancer specimens into nine clusters by immunohistochemical staining and 11 clusters using TCGA data. According to immunohistochemical staining, the high HER2 and FGFR2IIIb expression groups formed a cluster with high expression of various proteins. Analysis of stage 3-4 samples revealed more high protein expression clusters than the analysis of stage1-2, and this suggests that cancer acquires heterogeneity with cancer progression. In the TGCA data of stage 3-4, high FGFR2 and MET and high ERBB2 and SMAD2 or IGF1R expression formed clusters, which is consistent with the clustering analysis that was performed with immunohistochemical staining results. Conclusion: Our findings suggest that the existence of a combination of intratumoral heterogeneity and clusters may change with cancer progression. Citation Format: Gen Tsujio, Masakazu Yashiro, Yurie Yamamoto, Tomohiro Sera, Atsushi Sugimoto, Shuhei Kushiyama, Sadaaki Nishimura, Mami Yoshi, Tasuro Tamura, Takahiro Toyokawa, Hiroaki Tanaka, Shigeru Lee, Kazuya Muguruma, Masaichi Ohira. Analysis of intratumoral protein and gene expression heterogeneity in gastric cancer with a clustering analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3125.