Serum tumor markers are widely applied in the diagnosis, therapeutic effect assessment and disease recurrence monitoring[9]. A series of studies have explored the diagnostic and prognostic value of various serum tumor markers for gastric cancer[10]. However, most of these researches based on the patients undergone surgery with or without posttreatment, with only a few focusing on the patients with NCT in gastric cancer[11, 12].
From other researches, CA125 was associated with R0 resection rate[13], recurrence and peritoneal dissemination[14] and OS in the unresectable advanced or recurrent GC patients[15]; CA199 was related to pN[7, 16-18] and pTNM stage[17], and CA724 possessed the larger area under the receiver operating curve, which meant a higher diagnostic efficiency[19]. However, none of their patients underwent NCT.
In our study, not only the levels of CA199, CA125 and CA724 before and after NCT could predict the prognosis, but also the differences were related to the outcomes. Similar results had been put forward by many researches in GC patients without NCT[8, 13, 19, 20]. Nevertheless, we found that only CA724 was an independent prognostic marker in multivariable analysis. Notably, this independent significance decreased in the diff- group, which was a little different with some studies. Zou et al.[11] claimed that the change of CA724 could reflect the therapeutic effect of NCT. Another paper supported that a decrease in CA724 could lead to a better prognosis[12]. The distinction might due to we included more pathological factors in multivariable analysis. Despite of this, CA724 was still more specific and sensitive than other markers for GC patients undergone NCT.
Although CA724 owned a higher diagnostic value in GC, its sensitivity was only about 45.0%[19]. Moreover, in China, CA724 was claimed to associate with Helicobacter pylori infection[21] and even geographical environment factors, such as temperature[22]. These indicated that it was not enough to evaluate the condition of patients merely depend on CA724. To solve this problem, a lot of work had been done. For example, TKI, an enzyme involved in the regulation of the mammalian cell cycle, was another choice of marker in gastric cancer[19]. Or, the combination of CA724 with CA199, CA125 and CEA could also improve the capability of diagnosis[9, 12, 19, 23].
With regard to the pathological factors, we found that CA199, CA125 and CA724 before and after NCT were all predict indicators for lymph node metastasis and ypTNM stage. In the previous articles, in GC patients who experienced curative gastrectomy, preoperative CA199 could predict the lymph node metastasis[17, 18] and the pTNM stage[17]. CA724 was associated with nodal involvement[9] and worse stage in advanced gastric cancer patients[19]. As supplementary, we confirmed these in patients with preoperative therapy. In addition, we found CA125 as well as the change of CA125 was also related to ypN and ypTNM stage.
In our study, the VOLI rate was significantly higher in post-CA724 positive group, while in pre- group, the P value was closed to significant. However, Sun et al.[12] suggested that pre-CA724 was related to vascular invasion. This might suggest that CA724 could be used to assess the lymphatic or vascular invasion, but more researches are needed to distinguish the accuracy between pre- and post- groups.
It was unexpected that CEA was not related to prognosis in our study. Although a team from Japan supported a similar result[7], a large number of studies suggested the opposite one[10, 16, 18, 24]. Nevertheless, our CEA positive rate was related to the rising of CA199 and CA125, which had been raised before[7, 19]. Notably, these connections weakened after the NCT, which probably meant that the preoperative treatment could blur these relationships.
The limitations still exist in this study. Firstly, due to the nature of retrospective research, some patients did not have all values of markers, which hindered the exploration of the combination of markers. Secondly, the sample size was not large. The sample number of AFU and AFP in every group were so small that they were not included in the further analysis. This limitation might also contribute to the reason why some P values were more than 0.05 but smaller than 0.1. Thirdly, we used the optimal cutoff value derived from Youden index, which disturbed the comparation with other studies.
Despite of these limitations, our study still possesses some merits. Our sample size is relatively small, but we forced on specific group of patients. Although the optimal cutoff values have been agreed in patients without preoperational treatment, whether the borderline would change due to neoadjuvant therapy is still unknown. We not only illuminated the prognostic significance of these tumor markers, but confirmed their effects to predict lymph node metastasis and pathological stage. These results are useful for assessing the condition of patients and further clinical decision.