Skip to main content
Download PDF

CA19‑9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy

BMC Surgery volume 24, Article number: 31 (2024) Cite this article

Abstract

Background

Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 − 9 (CA19-9) and carbohydrate antigen 72 − 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy.

Methods

A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan–Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients.

Results

Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS.

Conclusion

Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

Peer Review reports

Introduction

Gastric cancer (GC) is a heterogeneous and highly aggressive malignant tumor, and it is the fourth leading cause of cancer-related death worldwide [1]. Because of its insidious onset, most GC patients are already in the advanced stage at the time of diagnosis rendening treatment difficult, with a high rate of recurrence and relatively poor prognosis [2, 3]. Radical gastrectomy with adjuvant chemotherapy is presently considered a standard treatment for stage II/III advanced GC patients [4]. However, the prognosis of GC patients undergoing radical gastrectomy remains poor [5,6,7]. Recurrence and distant metastasis are the main reason for death of GC patients after curative resection. Due to prognostic heterogeneity within each stage, identification of specific risk factors and accurate prediction for recurrence is warranted; this would help in performing appropriate intensive adjuvant therapies and in surveillance planning [8].

Serum tumor markers reflect tumor characteristics and burden generated by the tumor itself or in response to tumor cells [9, 10]. They have been used for GC screening and surveillance of relapse after radical surgery [11]. An increase in tumor markers is usually detected before clinical recurrence. Although many studies have reported that preoperative carcinoembryonic antigen (CEA), carbohydrate antigen 19 − 9 (CA19-9) and carbohydrate antigen 72 − 4 (CA72-4) can be used as prognostic factors [12, 13], their association with the prognosis and recurrence in different GC stages remains unclear. Thus, the aim of this study was to explore the prognostic significance of serum CEA, CA19-9 and CA72-4 levels for GC patients with stage I, II and III who underwent radical gastrectomy and their relationship with recurrence.

Materials and methods

Study population

A total of 580 GC patients who underwent radical gastrectomy at the Affiliated Hospital of XuZhou Medical University and Nanjing Gaochun People,s Hospital from August 2018 to August 2021 were retrospectively enrolled in this study. A diagnosis of GC was confirmed by histopathology, and TNM stage was staged in accordance with the 8th Edition of the American Joint Committee on Cancer (AJCC) classification. The protocol was approved by the Hospital Ethics Committee, and written informed consent was signed by all patients. Exclusion criteria included: (1) patients with previous or concomitant other cancer; (2) patients with non-radical surgery or distant metastases; (3) patients with prior history of neoadjuvant therapy; and (4) patients without key clinical variables or follow-up data.

Data collection and follow-up

Clinicopathological data including sex, age, tumor location, tumor size, pathologic type, degree of differentiation, nerve and vascular invasion, lymph node status and postoperative chemotherapy were recorded. Preoperative serum CEA, CA19-9 and CA72-4 levels (< 1 weeks before surgery) were recorded. The CA19-9 value less than 1 U/mL was excluded. For patients with recurrence, postoperative tumor marker levels (> 3 months after surgery) before recurrence were recorded during follow-up. For patients without recurrence, the postoperative tumor marker levels (> 3 months after surgery) before the end of follow-up were recorded during follow-up. The normal reference values of CEA, CA19-9 and CA72-4 were 5.0ng/ml, 35 U/ml and 6.9 U/ml, respectively. A test value above normal was considered positive. The positive results were defined when CEA (+) > 5.0 ng/mL, CA19-9 (+) > 35 U/mL and CA72-4 (+) > 6.9 U/mL. During the follow-up period, recurrence was confirmed by postoperative serum tumor biomarker levels, enhanced CT, gastroscopy and other relevant examinations. Overall survival (OS) was defined as the time from the date of surgery to the date of death or the end of follow-up (August 2022), and recurrence free survival (RFS) was the time interval between the date of surgery and the date of objective tumor relapse or the end of follow-up.

Statistical analysis

Categorical variables were analysed using Pearson chi-square tests or Fisher’s exact test. Kaplan-Meier survival curves were obtained by GraphPad Prism 8 software and compared with the log rank test. Univariate and multivariate analyses were performed to evaluate the independent risk factors associated with OS and PFS using the Cox proportional hazards model. The statistical analysis was performed using SPSS 26.0 (SPSS, Inc). The P value less than 0.05 was considered to be statistically significant.

Results

Patient characteristics

A total of 580 patients underwent radical gastrectomy, including 115 patients in stage I, 163 patients in stage II, and 302 patients in stage III. Of these patients, 423 were male and 157 were female. The median age was 65 years (range 32–86 years). The median follow-up duration was 29 months (range 9–45 months), and 86 patients (14.8%) died and 97 cases (16.7%) had a tumor recurrence.

Totally 9 patients in stage I, 73 patients in stage II, and 140 patients in stage III received postoperative adjuvant chemotherapy (PAC), of whom 1, 11 and 85 patients relapsed in stage I, II and III, respectively. The PAC regimen was SOX regimen (S-1 combined with oxaliplatin).

Correlation between CEA, CA19-9 and CA72-4 levels and recurrence in GC patients with stage I, II and III

The proportions of patients with preoperative and postoperative CEA (+) and CA19-9 (+) levels were significantly higher in those at stage III and with recurrence than that in patients at stage I and II (Tables 1 and 2). In addition, The RFS values were 99.1%, 89.1% and 58.3% for patients with stage I, II and III GC, respectively (Fig. 1a). Moreover, the OS values were 98.0%, 91.5% and 62.4% for GC patients with stage I, II and III, respectively (Fig. 1b). Kaplan-Meier survival analysis revealed that GC patients with stage III had a worse prognosis than those with stage I and II (Fig. 1). Further analysis showed that stage III GC patients with high pre- or postoperative levels of CEA, CA19-9 and CA72-4 trended to have lower RFS and OS, however, this difference was not significant in stage I and II GC patients (Fig. S). Therefore, we further analyzed the role of CEA, CA19-9 and CA72-4 levels in postoperative recurrence of patients with stage III GC.

Table 1 Positive rates of serum CEA, CA19-9 and CA72-4 levels
Full size table
Table 2 Recurrence rates in patients with positive tumor markers
Full size table
Fig. 1
figure 1

RFS curves (a) and OS curves (b) of GC patients with stage I, II and III

Full size image

The association between cancer recurrence and clinicopathological features in patients with stage III GC was summarized in Table 3. Preoperative CEA and CA19-9 levels, postoperative CEA, CA19-9 and CA72-4 levels, lymph node metastasis, and differentiation were associated with cancer recurrence. However, there was no significant association between recurrence and preoperative CA72-4 levels. The recurrence rates of patients with CEA > 5 ng/mL or CA19-9 > 35 U/mL were significantly higher than that of patients with CEA ≤ 5ng/mL or CA19-9 ≤ 35 U/mL(preoperative, 38.9% vs. 23.6%, 47.8% vs. 22.6%, respectively; postoperative, 48.6% vs. 21.5%, 66.7% vs. 21.9%, respectively; P < 0.05, Table 3).

Table 3 The relationship of recurrence and clinicopathological parameters in stage III GC
Full size table

Univariate and multivariate analysis in patients with stage III GC

Table 4 Univariate and multivariate analyses of clinicopathological factors for RFS in stage III GC
Full size table

The univariate analysis for RFS showed that preoperative CEA and CA19-9 levels, lymph node metastasis, postoperative CEA, CA19-9 and CA72-4 levels were significantly correlated with RFS in stage III GC (Table 4, all p < 0.05). Moreover, the univariate analysis for OS showed that preoperative CA19-9 levels, tumor size, nerve invasion, PAC, and postoperative CA19-9 and CA72-4 levels were significantly associated with OS in stage III GC (Table 5, all p < 0.05). Furthermore, in multivariate analysis, preoperative CA19-9 levels (HR:1.858; 95% CI:1.139–3.031; p = 0.013), lymph node metastasis (HR:2.502; 95% CI:1.138–5.503; p = 0.023), and postoperative CA19-9 (HR:2.464; 95% CI:1.393–4.359; p = 0.002) and CA72-4 (HR:2.555; 95% CI:1.473–4.432; p = 0.001) levels were significant independent prognosis factors for RFS in stage III GC; Preoperative CA19-9 levels (HR:1.878; 95% CI:1.121–3.147; p = 0.017), PAC (HR:0.550; 95% CI: 0.342–0.886; p = 0.014), and postoperative CA19-9 levels (HR:1.881; 95% CI: 1.081–3.270; p = 0.025) were significant independent factors for OS in stage III GC. Thus, the results indicated that CEA and CA72-4 were sometimes significant in preoperative or postoperative for RFS or OS. CA19-9 was always a significant factor both in univariate and multivariate analysis and for RFS or OS.

Table 5 Univariate and multivariate analyses of clinicopathological factors for OS in stage III GC
Full size table

Prognostic significance of preoperative and postoperative CA19-9 levels in patients with stage III GC

Multivariate analysis had showed that preoperative and postoperative CA19-9 levels were the significantly independent factors for RFS and OS. We further analyzed the prognostic impact of preoperative and postoperative CA19-9 levels in stage III GC. The patients were categorized into the following four groups according to preoperative and postoperative CA19-9 levels: preoperative CA19-9 ≤ 35 U/mL and postoperative CA19-9 > 35 U/mL, pre- and postoperative CA19-9 > 35 U/mL, pre- and postoperative CA19-9 ≤ 35 U/mL, preoperative CA19-9 > 35 U/mL and postoperative CA19-9 ≤ 35 U/mL. The Kaplan-Meier curves for RFS and OS in connection with CA19-9 values were shown in Fig. 2. The RFS of patients with preoperative high CA 19 - 9 that become negative after surgery were longer than that of patients always above 35 U/mL (Fig. 2a, p = 0.0015). The RFS of patients always under 35 U/mL were also longer than preoperative low CA19-9 that become positive after surgery (Fig. 2a, p < 0.001). The same trend was observed for OS (Fig. 2b). Thus, the results indicated that the patients with a elevated postoperative CA19-9 level had a poor prognosis.

Fig. 2
figure 2

Prognostic impact of pre- and postoperative CA19-9 levels in stage III GC. RFS curves (a) and OS curves (b)

Full size image

The RFS and OS of patients with preoperative high CA19-9 that become negative after surgery were lower than patients always under 35 U/mL (Fig. 2a-b, p = 0.0127, p < 0.001, respectively). Excluding the factor of postoperative adjuvant chemotherapy (PAC), the OS of patients with preoperative high CA19-9 was also significantly lower than that of patients with preoperative low CA19-9 (Fig. 3a-b, p = 0.0021, p = 0.0020, respectively). Thus, preoperative high CA19-9 levels also indicated poor outcomes.

Fig. 3
figure 3

Prognostic impact of preoperative CA19-9 levels of stage III GC patients with (a) or without (b) postoperative adjuvant chemotherapy (PAC)

Full size image

Discussion

Gastric cancer (GC) is a highly heterogeneous and aggressive malignant tumor with poor prognosis. Due to prognostic heterogeneity within each stage, identification of high-risk subgroups and individualized treatment is warranted. Previous study showed that tumor markers can be used in the diagnosis, prognosis, recurrence prediction and treatment response of GC [14]. They can also reflect tumor progression and burden. Therefore, this study investigated the prognostic value of serum CEA, CA19-9 and CA72-4 levels and their relationship with recurrence in patients with stage I, II and III GC who underwent radical gastrectomy.

Advanced gastric cancer patients are more likely to relapse and has a worse outcome after radical gastrectomy. Tumor markers have been reported as valuable predictors for the prognosis of gastric cancer. Our study suggested that CEA was significant only in univariate for RFS and CA72-4 was significant in univariate and multivariate for RFS at stage III GC. The only marker always significant for RFS and OS was CA19-9 that can be a useful marker for predicting outcome compared with CEA and CA72-4.

Carbohydrate antigen 19 − 9 (CA19-9), also called sialyl Lewis antigen A, has been widely used as a tumor-associated biomarker for the treatment of gastrointestinal malignancies, especially pancreatic cancer. Due to Lewis gene dysfunction or fucosyltransferase deficiency, approximately 5–10% of individuals are Lewis antigen negative, with no or low secretion of CA19-9 [15,16,17]. Therefore, we excluded GC patients with a CA19-9 value of less than 1 U/mL as in previous studies. Most previous studies only focused on the prognostic value of preoperative CA19-9 in GC. Few studies reported the value of pre- and postoperative CA19-9 in predicting prognosis and recurrence in stage III GC. A meta-analysis of 5,072 GC patients also showed that elevated serum CA19-9 was associated with poorer OS [18] as reported by many other studies [19,20,21,22] especially in stage III GC [23] or in association with pT and pN stage [24]. We did not find preoperative CEA or CA72-4 levels, pT stage were independent prognostic factors for OS and RFS. However, we found that pre- and postoperative CA19-9 were significant independent prognosis factors for RFS and OS in stage III GC.

In munivariate analysis, lymph node metastasis, postoperative CA72-4 were also significant independent factors for RFS in stage III GC. Eom BW et al. reported that LN metastasis and venous invasion were independent predictors of early recurrence [25]. Kang WM et al. also reported that patient age, pT stage, pN stage, Lauren histotype, lymphovascular invasion, intraoperative chemotherapy, and postoperative chemotherapy were independent predictors of early recurrence in patients with pT2-4a stage GC [26]. Wakatsuki Ket al. also reported that pN ≥ 14 and preoperative CA19-9 were independent risk factors for ERec (early recurrence within 12 months) after curative gastrectomy in pStage III GC [27]. A previous study of 1179 GC patients showed that pre- or postoperative CA72-4 was independently associated with shorter OS and RFS [28]. Consistent with previous findings, our study also suggested that lymph node metastasis was a risk factor for recurrence in GC patients. However, in our study preoperative CA72-4 was not an independent factors for RFS and OS in stage III GC, so further study is needed.

Multivariate analysis also showed that postoperative adjuvant chemotherapy (PAC) was a significant independent protective factor for OS in stage III GC. This indicated that PAC was beneficial to the prognosis of stage III GC patients. A previous study reported that adjuvant chemotherapy can improve the survival rate and disease-free survival rate of GC patients, and reduce the relapse rate after curative resection [29]. Randomized phase III trials showed that postoperative adjuvant therapy with S-1 or S-1 plus docetaxel could improve OS and RFS in patients with stage III GC who had undergone D2 gastrectomy [30, 31]. In addition, stage III GC patients with preoperative high CA19-9 that become negative after surgery had longer RFS and OS, but lower than patients always under 35 U/ml. Therefore, monitor the preoperative and postoperative CA19-9 levels in stage III GC patients is of great value for evaluating the treatment effect, predicting recurrence and prognosis. Due to preoperative or postoperative high CA19-9 levels all indicated poor outcomes. Thus, intensive postoperative anticancer management should be received.

This study had a few limitations. First, this was a retrospective study from two institutions with a possible selection bias and a relatively small samples. Second, follow-up period was short, and some cases were followed up for less than 3 years. Third, the comorbidities and postoperative complications were not investigated in this study, which could also affect the prognosis. Thus, a prospective, multicentre study with longer follow-up period is urgently needed for further investigation.

Conclusions

This study showed preoperative and postoperative CA19-9 levels to be independent risk factors for predicting prognosis in stage III GC after curative gastrectomy. Patients with higher CA19-9 values should hence be considered for receiving intensive perioperative anticancer management following curative resections owing to the poor prognosis.

Data availability

The datasets of the current study are available from the corresponding author upon reasonable request.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci. 2020;21:4012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sasahara M, Kanda M, Kodera Y. Update on molecular biomarkers for diagnosis and prediction of prognosis and treatment responses in gastric cancer. Histol Histopathol. 2021;36:817–32.

    CAS  PubMed  Google Scholar 

  4. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2021 (6th edition). Gastric Cancer. 2023;26(1):1–25.

    Article  Google Scholar 

  5. D’Angelica M, Gonen M, Brennan MF, Turnbull AD, Bains M, Karpeh MS. Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004;240:808–16.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shiraishi N, Inomata M, Osawa N, Yasuda K, Adachi Y, Kitano S. Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and multivariate analyses. Cancer. 2000;89:255–61.

    Article  CAS  PubMed  Google Scholar 

  7. Sakar B, Karagol H, Gumus M, Basaran M, Kaytan E, Argon A, Ustuner Z, Bavbek SE, Bugra D, Aykan FN. Timing of death from tumor recurrence after curative gastrectomy for gastric cancer. Am J Clin Oncol. 2004;27:205–9.

    Article  PubMed  Google Scholar 

  8. Mizuno H, Miyake H, Nagai H, Yoshioka Y, Shibata K, Asai S, Takamizawa J, Yuasa N. Optimal cutoff value of preoperative CEA and CA19-9 for prognostic significance in patients with stage II/III colon cancer. Langenbecks Arch Surg. 2021;406:1987–97.

    Article  PubMed  Google Scholar 

  9. Nagpal M, Singh S, Singh P, Chauhan P, Zaidi MA. Tumor markers: a diagnostic tool. Natl J Maxillofac Surg. 2016;7:17–20.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kotzev AI, Draganov PV. Carbohydrate antigen 19 – 9, carcinoembryonic antigen, and carbohydrate antigen 72 – 4 in gastric cancer: is the old band still playing? Gastrointest Tumors. 2018;5:1–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Whiting J, Sano T, Saka M, Fukagawa T, Katai H, Sasako M. Follow-up of gastric cancer: a review. Gastric Cancer. 2006;9:74–81.

    Article  PubMed  Google Scholar 

  12. Shimada H, Noie T, Ohashi M, Oba K, Takahashi Y. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the task force of the Japanese gastric cancer association. Gastric Cancer. 2014;17:26–33.

    Article  CAS  PubMed  Google Scholar 

  13. Moriyama J, Oshima Y, Nanami T, Suzuki T, Yajima S, Shiratori F, Funahashi K, Shimada H. Prognostic impact of CEA/CA19-9 at the time of recurrence in patients with gastric cancer. Surg Today. 2021;51:1638–48.

    Article  CAS  PubMed  Google Scholar 

  14. Matsuoka T, Yashiro M. Biomarkers of gastric cancer: current topics and future perspective. World J Gastroenterol. 2018;24:2818–32.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liu C, Deng S, Jin K, Gong Y, Cheng H, Fan Z, Qian Y, Huang Q, Ni Q, Luo G, Yu X. Lewis antigennegative pancreatic cancer: an aggressive subgroup. Int J Oncol. 2020;56:900–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Guo M, Luo G, Lu R, Shi W, Cheng H, Lu Y, Jin K, Yang C, Wang Z, Long J, Xu J, Ni Q, Liu C, Yu X. Distribution of Lewis and Secretor polymorphisms and corresponding CA19-9 antigen expression in a Chinese population. FEBS Open Bio. 2017;7:1660–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Scarà S, Bottoni P, Scatena R. CA 19 – 9: biochemical and clinical aspects. Adv Exp Med Biol. 2015;867:247–60.

    Article  PubMed  Google Scholar 

  18. Xiao J, He X, Wang Z, Hu J, Sun F, Qi F, Yang S, Xiao Z. Serum carbohydrate antigen 19 – 9 and prognosis of patients with gastric cancer. Tumour Biol. 2014;35:1331–4.

    Article  CAS  PubMed  Google Scholar 

  19. Song YX, Huang XZ, Gao P, Sun JX, Chen XW, Yang YC, Zhang C, Liu HP, Wang HC, Wang ZN. Clinicopathologic and prognostic value of serum carbohydrate antigen 19 – 9 in gastric cancer: a meta-analysis. Dis Markers. 2015;2015:549843.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yin HH, Xu MQ, Liu BZ, Tao L, Ma YJ, Li F, Zhang WJ. Combination of preoperative CA19-9 levels, cell differentiation, and age predicts survival for patients with gastric cancer before surgery. Med (Baltim). 2021;100:e28017.

    Article  CAS  Google Scholar 

  21. Kodera Y, Yamamura Y, Torii A, Uesaka K, Hirai T, Yasui K, Morimoto T, Kato T, Kito T. The prognostic value of preoperative serum levels of CEA and CA19-9 in patients with gastric cancer. Am J Gastroenterol. 1996;91:49–53.

    CAS  PubMed  Google Scholar 

  22. You W, Cai Z, Sheng N, Yan L, Wan H, Wang Y, Ouyang J, Xie L, Wu X, Wang Z. Construction and validation of convenient clinicopathologic signatures for predicting the prognosis of stage I-III gastric cancer. Front Oncol. 2022;12:848783.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kambara Y, Miyake H, Nagai H, Yoshioka Y, Shibata K, Asai S, Yuasa N. CA19-9 is a significant prognostic marker of patients with stage III gastric cancer. Eur J Surg Oncol. 2020;46:1918–24.

    Article  PubMed  Google Scholar 

  24. Lin JX, Wang W, Lin JP, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu R, Zheng CH, Huang CM, Zhou ZW, Li P. Preoperative tumor markers independently predict survival in stage III gastric cancer patients: should we include tumor markers in AJCC staging? Ann Surg Oncol. 2018;25:2703–12.

    Article  PubMed  Google Scholar 

  25. Eom BW, Yoon H, Ryu KW, Lee JH, Cho SJ, Lee JY, Kim CG, Choi IJ, Lee JS, Kook MC, Park SR, Nam BH, Kim YW. Predictors of timing and patterns of recurrence after curative resection for gastric cancer. Dig Surg. 2010;27:481–6.

    Article  PubMed  Google Scholar 

  26. Kang WM, Meng QB, Yu JC, Ma ZQ, Li ZT. Factors associated with early recurrence after curative surgery for gastric cancer. World J Gastroenterol. 2015;21:5934–40.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wakatsuki K, Matsumoto S, Migita K, Kunishige T, Nakade H, Miyao S, Sho M. Risk factors and risk scores for predicting early recurrence after curative gastrectomy in patients with stage III gastric cancer. J Gastrointest Surg. 2020;24:1758–69.

    Article  PubMed  Google Scholar 

  28. Wu T, Wang CH, Wang W, Liu LL, Yun JP, Zhou ZW. Association of preoperative and postoperative CA72-4 with gastric cancer outcome. J Surg Oncol. 2021;123:1699–707.

    Article  CAS  PubMed  Google Scholar 

  29. Cao J, Qi F, Liu T. Adjuvant chemotherapy after curative resection for gastric cancer: a meta-analysis. Scand J Gastroenterol. 2014;49:690–704.

    Article  CAS  PubMed  Google Scholar 

  30. Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93.

    Article  CAS  PubMed  Google Scholar 

  31. Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022;25:188–96.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research was supported by Science and Technology Project of Xuzhou Municipal Health Commission (XWKYHT20220152) and Clinical Medical Science and Technology Development Fund of Jiangsu University (JLY2021176).

Author information

Author notes

  1. Xiao Ma and Xiaohua Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, #99 Huaihai Xi Road, JiangSu, Xuzhou, 221002, China

    Xiao Ma, Jiaxuan Guo, Xinyu Feng, Mengmeng Zhao, Peng Zhang, Chong Zhang, Shuai Gong, Nai Wu, Yi Zhang, Xiuzhong Zhang, Zeqiang Ren & Pengbo Zhang

  2. Department of General Surgery, Nanjing Gaochun People’s Hospital, #53 Maoshan Road, Gaochun Economic Development Zone, JiangSu, Nanjing, 211300, China

    Xiaohua Zhou

Authors
  1. Xiao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaohua Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiaxuan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xinyu Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mengmeng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shuai Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nai Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiuzhong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Zeqiang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pengbo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Pengbo Zhang, Zeqiang Ren and Xiao Ma participated in the study conception and design. Xiao Ma, Xiaohua Zhou and Peng Zhang participated in the acquisition of data. Xiao Ma and Xiaohua Zhou participated in the analysis and interpretation of data. Xiao Ma and Pengbo Zhang participated in the drafting of the manuscript. Xiuzhong Zhang, Chong Zhang, Shuai Gong, Nai Wu, Yi Zhang, Jiaxuan Guo, Xinyu Feng and Mengmeng Zhao participated in the critical revision of the manuscript.

Corresponding authors

Correspondence to Zeqiang Ren or Pengbo Zhang.

Ethics declarations

Ethics approval and consent to participate

The retrospective study complied with the declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Hospital of XuZhou Medical University and Nanjing Gaochun People’s Hospital. Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1: Figure S

Prognostic impact of serum tumor markers. A and B: Overall and recurrence-free survival curves according to preoperative CEA, CA19-9 and CA72-4 levels; C and D: Overall and recurrence-free survival curves according to postoperative CEA, CA19-9 and CA72-4 levels. CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9. CA72-4: Carbohydrate antigen 72-4

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, X., Zhou, X., Guo, J. et al. CA19‑9 is a significant prognostic factor in stage III gastric cancer patients undergoing radical gastrectomy. BMC Surg 24, 31 (2024). https://doi.org/10.1186/s12893-024-02324-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12893-024-02324-3

Keywords

BMC Surgery

ISSN: 1471-2482

Contact us