The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC)

核苷酸还原酶调节亚基 M1 (RRM1) 蛋白的免疫组织化学过度表达是晚期非小细胞肺癌 (NSCLC) 接受吉西他滨化疗后生存期较短的预测因素

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作者:Jae Jin Lee, Chi Hoon Maeng, Seon Kyung Baek, Gou Young Kim, Jee-Hong Yoo, Cheon Woong Choi, Yee Hyung Kim, Young-Tae Kwak, Dae-Hyun Kim, Young Kyung Lee, Jung Bo Kim, Si-Young Kim

Abstract

We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.

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