Wu Yan, Li Yafang, Liu Junqiang, Chen Mengjiao, Li Wei, Chen Yongchang, Xu Min
Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, China.
Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Transl Cancer Res. 2020 Jun;9(6):3870-3878. doi: 10.21037/tcr-20-764.
For the biomarkers of cancer, many chromosomal and genetic alterations have been examined as possible. However, some tumors do not display a clear molecular and genetic signature. While there are some cellular processes regulated by second messenger intracellular pathways indeed involved in carcinogenesis. The first intracellular second messenger was described as cyclic adenosine 3',5'-monophosphate (cAMP), and cAMP-dependent protein kinase (PKA) play a crucial role in several biological processes; The dysregulation of PKA-mediated signaling in several types of cancer should be investigated. More interesting, the alpha catalytic subunit of PKA (PKACα) could be secreted into the conditioned medium by different types of cancer cells, and it also existed in the serum of some cancer patients, defined as extracellular protein kinase A (ECPKA).
The levels of serum PKACα from healthy people, gastric cancer and colon cancer patients were detected by ELISA kits. Western blotting was used to detect the expression of PKACα in cancer tissue and the adjacent mucosa. Mann-Whitney test was applied to analyze the patients' characteristics and serum PKACα. ROC analyses were performed to further evaluate the utility of PKACα in cancer diagnosis. The correlation of serum PKACα and T stage, age, and tumor markers were analyzed by Spearman rank and Pearson correlation analysis, respectively.
There were significant differences of PKACα in serum between the volunteers and the gastric cancers (P<0.01), but not the colorectal cancers (P>0.05). ROC analyses evaluated the utility of PKACα for gastric cancer with 61.90% sensitivities and 87.50% specificities. The serum PKACα was correlated with tumor marker CA50, while there was no significant difference of PKACα expression between the gastric/colorectal cancer tissue and the adjacent mucosa.
The above results implied that PKACα levels might be a potential biomarker for the early screening of gastric cancers. Moreover, further research is still needed to investigate the role of secreted PKACα and the regulatory mechanism in tumor progression.
对于癌症生物标志物，人们已对许多染色体和基因改变进行了检测。然而，一些肿瘤并未表现出明确的分子和基因特征。虽然确实有一些由细胞内第二信使途径调节的细胞过程参与了致癌作用。第一个细胞内第二信使被描述为环磷酸腺苷（cAMP），且cAMP依赖性蛋白激酶（PKA）在多个生物学过程中起关键作用；应研究PKA介导的信号通路在几种癌症类型中的失调情况。更有趣的是，PKA的α催化亚基（PKACα）可被不同类型的癌细胞分泌到条件培养基中，并且它也存在于一些癌症患者的血清中，被定义为细胞外蛋白激酶A（ECPKA）。
使用ELISA试剂盒检测健康人、胃癌和结肠癌患者血清中PKACα的水平。采用蛋白质印迹法检测癌组织及相邻黏膜中PKACα的表达。应用曼-惠特尼检验分析患者特征与血清PKACα。进行ROC分析以进一步评估PKACα在癌症诊断中的效用。分别通过Spearman秩相关分析和Pearson相关分析血清PKACα与T分期、年龄及肿瘤标志物的相关性。
志愿者与胃癌患者血清中的PKACα存在显著差异（P<0.01），但与结直肠癌患者血清中的PKACα无显著差异（P>0.05）。ROC分析评估PKACα对胃癌诊断的效用，敏感性为61.90%，特异性为87.50%。血清PKACα与肿瘤标志物CA50相关，而胃癌/结直肠癌组织与相邻黏膜中PKACα的表达无显著差异。
上述结果表明，PKACα水平可能是胃癌早期筛查的潜在生物标志物。此外，仍需进一步研究来探讨分泌型PKACα的作用及其在肿瘤进展中的调控机制。
