LAUSR

The paper “High SPINK1 expression predicts poor prognosis and promotes cell proliferation and metastasis of hepatocellular carcinoma” evaluates the prognostic value and role of serine protease inhibitor Kazal type I (SPINK1) in the proliferation and metastatic potential of hepatocellular carcinoma (HCC) [1]. The identity of SPINK1 is that of a small secreted protein, which, however, could be characterized by many in the scientific world as “double-faced”, since in different environments and situations it can have very different, if not opposing, roles. Specifically, on one hand in its role as a pancreatic secretory trypsin inhibitor that is produced by pancreatic acinar cells, it can prevent organ damage in pancreatitis by inhibiting early activation of trypsinogen to trypsin [2]. As a result, mutations of SPINK1 lead to episodes of chronic pancreatitis and/or pancreatic insufficiency [3]. On the other hand, when SPINK1 is found outside the normal pancreas, and especially in a tumor microenvironment, it has been shown to be over expressed by a significant number of different tumor cells, including prostate, breast, pancreas and colon, while at the same time it has been intimately associated with chemoresistance and increased risk of tumor recurrence [4, 5]. The dual roles of SPINK1 make it an ideal target for therapeutic interventions; however, before that happens, it is essential to understand its identity and function better. Specifically, it would be useful to elucidate the mechanisms involved in its versatile function. Huang et al. [1] in this paper show us that high SPINK1 expression predicts poor prognosis and is possibly involved in metastasis in hepatocellular carcinoma. What is more important is the fact that they investigate and present possible mechanisms involved, including HCC cell proliferation, migration and invasion, as well as involvement of glycine, serine, threonine and bile acid metabolism. This will be critical in the effort to identify targets for a more precise approach against HCC. In addition, the authors are able to achieve their goals using an elegant experimental plan with the combination of tissue micro-arrays to identify the differential expression between HCC and normal tissue, as well as by using the Cancer Genome Atlas (TCGA) database and Gene set enrichment analysis (GSEA) to verify the prognostic value of SPINK1 in HCC. The importance of this lies in the fact that it showcases how molecular analysis and targeting can lead to a more patient-targeted, personalized approach, which is the essential goal of precision medicine.