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Inamura, Kentaro

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Inamura

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Kentaro

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Inamura, Kentaro

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2015 - 20162

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Author's Publications: search.filters.isAuthorOfPublication.54bd5cd7-31dc-445c-be59-3de5cb10d761

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    Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma
    (Cell Press, 2016) Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A.; Qian, Zhi Rong; Cohen, Ofir; Nakashima, Reiko; Bahl, Samira; Cao, Yin; Amin-Mansour, Ali; Yamauchi, Mai; Sukawa, Yasutaka; Stewart, Chip; Rosenberg, Mara; Mima, Kosuke; Inamura, Kentaro; Nosho, Katsuhiko; Nowak, Jonathan A.; Lawrence, Michael S.; Giovannucci, Edward L.; Chan, Andrew T.; Ng, Kimmie; Meyerhardt, Jeffrey A.; Van Allen, Eliezer M.; Getz, Gad; Gabriel, Stacey B.; Lander, Eric S.; Wu, Catherine J.; Fuchs, Charles S.; Ogino, Shuji; Garraway, Levi A.
    Summary Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.
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    Survival Benefit of Exercise Differs by Tumor IRS1 Expression Status in Colorectal Cancer
    (Springer Nature, 2015-11-17) Hanyuda, Akiko; Kim, Sun A.; Martinez-Fernandez, Alejandro; Qian, Zhi Rong; Yamauchi, Mai; Nakashima, Reiko; Morikawa, Teppei; Liao, Xiaoyun; Inamura, Kentaro; Mima, Kosuke; Cao, Yin; Zhang, Xuehong; Wu, Kana; Chan, Andrew T.; Ogino, Shuji; Giovannucci, Edward; Meyerhardt, Jeffrey; Fuchs, Charles; Shivdasani, Ramesh
    Background. High-level physical activity is associated with lower colorectal cancer (CRC) mortality, likely through insulin sensitization. Insulin receptor substrate 1 (IRS1) is a mediator of insulin and insulin-like growth factor (IGF) signaling pathways, and its down-regulation is associated with insulin resistance. Therefore, we hypothesized that tumor IRS1 expression status might modify cellular sensitivity to insulin and IGF, and the prognostic association of physical activity.Methods. We assessed IRS1 expression level in 371 stage I-III rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study by immunohistochemistry. In survival analysis, Cox proportional hazards model was used to assess an interaction between post-diagnosis physical activity (ordinal scale of sex-specific quartiles Q1 to Q4) and IRS1 expression (ordinal scale of negative, low, and high), controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation level, and KRAS, BRAF, and PIK3CA mutation status.Results. There was a statistically significant interaction between post-diagnosis physical activity and tumor IRS1 expression in CRC-specific mortality analysis (P-interaction = 0.005). Multivariable hazard ratio (95 % confidence interval) for higher post-diagnosis physical activity (Q3-Q4 vs. Q1-Q2) was 0.15 (0.02-1.38) in the IRS1-negative group, 0.45 (0.19-1.03) in the IRS1-low group, and 1.32 (0.50-3.53) in the IRS1-high group.Conclusions. The association of post-diagnosis physical activity with colorectal carcinoma patient survival may differ by tumor IRS1 expression level. If validated, tumor IRS1 expression status may serve as a predictive marker to identify subgroups of patients who might gain greater survival benefit from an increased level of exercise.