Increased expression of antisense lncRNA SPINT1-AS1 predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript.
Increased expression of antisense lncRNA SPINT1-AS1 predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript.
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反义lncRNA SPINT1-AS1表达增加预示结直肠癌预后不良，并与其正义转录本呈负相关
DOI：
10.2147/ott.s163883
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发表时间：
2018
影响因子：
4
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Li C;Li W;Zhang Y;Zhang X;Liu T;Zhang Y;Yang Y;Wang L;Pan H;Ji J;Wang C
结直肠癌（CRC）是全球癌症相关死亡率的主要原因。天然反义转录物（NAT）在人类基因组中广泛表达，并已被证实有助于癌症的进展。本研究旨在探讨丝氨酸肽酶抑制剂Kunitz 1型反义RNA 1（SPINT 1-AS 1）在结直肠癌中的表达及其临床意义。通过链特异性实时定量聚合酶链反应分析了150对CRC组织和邻近正常（AN）组织中SPINT 1-AS 1和相应正义转录物SPINT 1 mRNA的表达水平，沿着45对术前和术后血清外泌体样本。结直肠癌组织中SPINT 1-AS 1的表达高于结直肠癌组织（P<0.001，3.771 vs 0.980），而SPINT 1 mRNA的表达低于结直肠癌组织（P<0.001，0.927 vs 1.165），且SPINT 1-AS 1的表达与其正义转录本呈明显负相关（r=-0.701，P <0.001）。SPINT 1-AS 1产生用于区分CRC组织与AN组织的0.865（95%置信区间，0.821-0.902）的受试者工作特征曲线下面积值。SPINT 1-AS 1高表达与区域淋巴结转移（P<0.001）、远处转移（P<0.001）、无复发生存期（RFS）缩短（P<0.001）相关，考克斯回归分析显示SPINT 1-AS 1是影响RFS的独立预后因素。同时，在手术切除后的CRC血清外泌体中观察到SPINT 1-AS 1表达水平显著降低（P=0.001）。SPINT 1-AS 1在CRC组织中上调，并在CRC进展和预后中起重要作用。因此，SPINT 1-AS 1可能作为CRC的候选预后生物标志物和分子治疗靶点。
Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Natural antisense transcripts (NATs) are pervasively expressed in human genome and have been confirmed to contribute to cancer progression. In our study, we aimed to investigate the expression and clinical pertinence of serine peptidase inhibitor, Kunitz type 1 antisense RNA1 (SPINT1-AS1) in CRC. The expression levels of SPINT1-AS1 and the corresponding sense transcript SPINT1 mRNA were analyzed in 150 pairs of CRC tissues and adjacent normal (AN) tissues, along with 45 pairs of preoperative and postoperative serum exosome samples by the strand-specific real-time quantitative polymerase chain reaction. Compared with AN tissues, the expression of SPINT1-AS1 was increased (P<0.001, 3.771 vs 0.980) in CRC tissues, while SPINT1 mRNA expression was decreased in CRC (P<0.001, 0.927 vs 1.165), and there was an obviously negative correlation between SPINT1-AS1 expression and its sense transcript (r=−0.701, P<0.001). SPINT1-AS1 yielded an area under the receiver operating characteristic curve value of 0.865 (95% confidence interval, 0.821–0.902) for discriminating CRC tissues from AN tissues. Moreover, high SPINT1-AS1 expression was correlated with regional lymph node metastasis (P<0.001), distant metastasis (P<0.001), and shorter relapse-free survival (RFS) time (P<0.001), and Cox regression analysis indicated that SPINT1-AS1 was an independent prognostic factor for RFS. Meanwhile, significant reduction of SPINT1-AS1 expression level (P=0.001) was observed in CRC serum exosomes after surgical resection. SPINT1-AS1 is upregulated in CRC tissues and plays an essential role in CRC progression and prognosis. Thereby, SPINT1-AS1 may serve as a candidate prognostic biomarker and molecular therapy target for CRC.