Increased expression of antisense lncRNA SPINT1-AS1 predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.