Kuramochi Hidekazu, Nakamura Ayako, Nakajima Go, Kaneko Yuka, Araida Tatsuo, Yamamoto Masakazu, Hayashi Kazuhiko
Department of Chemotherapy and Palliative Care, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo, Japan.
Department of Surgery, Tokyo Women's Medical University, Yachiyo Medical Center, 477-96 Owadashinden, Yachiyoshi, Chiba, 276-8524, Japan.
BMC Cancer. 2016 Jun 13;16:366. doi: 10.1186/s12885-016-2400-4.
Several recent studies have reported that patients with metastatic colorectal cancer (CRC) whose primary tumor is located in left side of the colon have more favorable responses to anti-epidermal growth factor receptor (EGFR) antibody therapy than those with right-sided tumors. However, the mechanism for this phenomenon is unknown.
Fifty-two cases of primary CRC with liver metastases were analyzed in this retrospective study. The mRNA levels of 19 signal transduction genes in both primary tumor and liver metastases were measured by real-time reverse transcription polymerase chain reaction. The purposes of this study were (1) to determine the correspondence between signal transduction gene expressions in primary tumors and corresponding liver metastases, and (2) to determine whether expression levels of these genes differ by primary tumor location.
mRNA expression levels of 14 of 19 signal transduction genes, including PTEN, ERBB2, MET, HGF, AREG, and EREG, showed significant correlations between the primary tumor and corresponding liver metastases. When the mRNA levels of the primary tumors were compared by tumor location, only PTEN mRNA expression differed significantly between left and right-sided CRC (median PTEN expression: left 1.00 vs. right 1.68; p = 0.017). When rectal cancers were separated from left-sided colon cancers, PTEN mRNA levels increased progressively from rectum to right-sided colon (median; rectum 0.84, left colon 1.23, right colon 1.68, p = 0.013). PTEN mRNA expression in liver metastases also differed significantly according to primary tumor location (median; left 0.92 vs. right 1.27, p = 0.048). There was no difference in overall survival between patients with high versus low levels of PTEN mRNA (p = 0.59).
Our data suggest that the PIK3/AKT/mTOR pathway is more active in left- than right-sided CRC, which provides a possible explanation for the fact that efficacy of anti-EGFR therapy differs by location of primary tumor.
最近的几项研究报告称，原发性肿瘤位于结肠左侧的转移性结直肠癌（CRC）患者对比右侧肿瘤患者，对抗表皮生长因子受体（EGFR）抗体治疗的反应更佳。然而，这一现象的机制尚不清楚。
本回顾性研究分析了52例伴有肝转移的原发性CRC病例。通过实时逆转录聚合酶链反应测量原发性肿瘤和肝转移灶中19个信号转导基因的mRNA水平。本研究的目的是：（1）确定原发性肿瘤与相应肝转移灶中信号转导基因表达之间的对应关系；（2）确定这些基因的表达水平是否因原发性肿瘤位置而异。
19个信号转导基因中的14个，包括PTEN、ERBB2、MET、HGF、AREG和EREG，其mRNA表达水平在原发性肿瘤与相应肝转移灶之间显示出显著相关性。当按肿瘤位置比较原发性肿瘤的mRNA水平时，仅PTEN mRNA表达在左侧和右侧CRC之间存在显著差异（PTEN表达中位数：左侧1.00对右侧1.68；p = 0.017）。当直肠癌与左侧结肠癌分开时，PTEN mRNA水平从直肠到右侧结肠逐渐升高（中位数；直肠0.84，左结肠1.23，右结肠1.68，p = 0.013）。肝转移灶中的PTEN mRNA表达也因原发性肿瘤位置而有显著差异（中位数；左侧0.92对右侧1.27，p = 0.048）。PTEN mRNA水平高与低的患者之间总生存期无差异（p = 0.59）。
我们的数据表明，PIK3/AKT/mTOR通路在左侧CRC中比右侧更活跃，这为抗EGFR治疗疗效因原发性肿瘤位置而异这一事实提供了一种可能的解释。
