講演情報
[P3-1-5]大腸癌におけるHSPB1タンパク発現の臨床的意義と5FU感受性変化に関する検証
志村 匡信1, 北嶋 貴仁1,2, 家城 英治1, 水野 成1, 山下 真司1, 今岡 裕基1, 川村 幹雄1, 大北 喜基1, 嶌村 麻生1, 市川 崇1, 浦谷 亮1, 安田 裕美1, 小池 勇樹1, 吉山 繁幸1, 大井 正貴1, 奥川 喜永1,2, 問山 裕二1 (1.三重大学大学院消化管小児外科学, 2.三重大学病院ゲノム診療科)
【Background and Aims】 While heat shock protein beta-1（HSPB1）is one of a negative regulators of ferroptosis, the clinical importance and mechanistic impact of HSPB1 has not fully elucidated in colorectal cancer（CRC）.
【Methods】 We first evaluated the protein expression of HSPB1 in a clinical cohort of 156 CRC patients by immunohistochemistry（IHC）. By using IHC score（multiplying staining intensity and staining proportion）, we divided patients into high and low HSPB1 expression group dichotomized by Youden index for overall survival（OS）and recurrence free survival（RFS）. Then we evaluated the prognostic impact of HSPB1 expression with regard to OS/RFS. Furthermore, after si-transfection of HSPB1 using two CRC cells（DLD-1 and SW480）, we assessed the alteration of cytotoxic effect of 5-fluorouracil（5FU）based on the IC50 concept by performing WST8 assay.
【Results】
HSPB1 expression was remarkably stronger in the cytoplasm of colorectal tumor tissue. High HSPB1 expression was associated with advanced T, N, and M factor（p＜0.01, respectively）. Kaplan meier analysis revealed that the patients with HSPB1 high expression showed significantly poorer OS and RFS（p＜0.01, respectively）. Then, univariate and multivariate analysis demonstrated that HSPB1 high expression was identified as an independent risk factor for poorer OS and RFS（p=0.006, and p＜0.001, respectively）. Furthermore, intriguingly, IC50 values of 5FU were decreased by transfecting HSPB1（DLD-1；from 106.03 uM to 67.62 uM, SW480；67.61 uM to 18.93 uM）in CRC cells.
【Conclusion】
We demonstrated that HSPB1 may serve as a robust prognostic- and recurrence-predictive biomarker in CRC patients, and HSPB1 possess important roles in attenuating the cytotoxic effect of 5FU based chemotherapy in CRC cells.
【Methods】 We first evaluated the protein expression of HSPB1 in a clinical cohort of 156 CRC patients by immunohistochemistry（IHC）. By using IHC score（multiplying staining intensity and staining proportion）, we divided patients into high and low HSPB1 expression group dichotomized by Youden index for overall survival（OS）and recurrence free survival（RFS）. Then we evaluated the prognostic impact of HSPB1 expression with regard to OS/RFS. Furthermore, after si-transfection of HSPB1 using two CRC cells（DLD-1 and SW480）, we assessed the alteration of cytotoxic effect of 5-fluorouracil（5FU）based on the IC50 concept by performing WST8 assay.
【Results】
HSPB1 expression was remarkably stronger in the cytoplasm of colorectal tumor tissue. High HSPB1 expression was associated with advanced T, N, and M factor（p＜0.01, respectively）. Kaplan meier analysis revealed that the patients with HSPB1 high expression showed significantly poorer OS and RFS（p＜0.01, respectively）. Then, univariate and multivariate analysis demonstrated that HSPB1 high expression was identified as an independent risk factor for poorer OS and RFS（p=0.006, and p＜0.001, respectively）. Furthermore, intriguingly, IC50 values of 5FU were decreased by transfecting HSPB1（DLD-1；from 106.03 uM to 67.62 uM, SW480；67.61 uM to 18.93 uM）in CRC cells.
【Conclusion】
We demonstrated that HSPB1 may serve as a robust prognostic- and recurrence-predictive biomarker in CRC patients, and HSPB1 possess important roles in attenuating the cytotoxic effect of 5FU based chemotherapy in CRC cells.