Analysis and exploration of the association between serum tumor marker status and clinical pathological features, as well as efficacy, in colorectal cancer

Xing,Zhenzhu; Xiao,Yifan; Li,Shaobing; Jia,Gang; Cheng,Peng; Chen,Yuming; Zhou,Jianwei; Sun,Liang; Lu,Chuangxin

doi:10.3892/ol.2025.15184

Analysis and exploration of the association between serum tumor marker status and clinical pathological features, as well as efficacy, in colorectal cancer

Authors:
- Zhenzhu Xing
- Yifan Xiao
- Shaobing Li
- Gang Jia
- Peng Cheng
- Yuming Chen
- Jianwei Zhou
- Liang Sun
- Chuangxin Lu
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Affiliations: Department of Oncology, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou, Henan 450003, P.R. China, Department of Oncology, Henan University People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Medical Records Management, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Oncology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China, School of Public Health, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China
Published online on: July 9, 2025 https://doi.org/10.3892/ol.2025.15184
Article Number: 438
Copyright: © Xing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) remains a major global health challenge, necessitating improved prognostic and predictive tools. The aim of the present study was to investigate the associations between elevated serum tumor markers (TMs) and clinicopathological features in patients with colorectal cancer, to evaluate their prognostic ability in advanced‑stage disease cases and to identify patients most likely to respond to treatment. This retrospective study analyzed data from 293 patients treated for colorectal adenocarcinoma between January 1, 2020, and June 30, 2023. Carcinoembryonic antigen and cancer antigen (CA)19‑9, CA72‑4 and CA125 positivity were evaluated to classify patients into negative, single elevation (higher expression than normal in 1 TM) and multiple elevation (≥2 TMs expressed at higher than normal levels) groups. Clinical characteristics were evaluated using χ² tests, and a Kaplan‑Meier survival analysis was conducted. The number of elevated TMs was associated with T stage (P=0.01), poor differentiation (P<0.001), later clinical stages (P<0.001), metastatic sites (P<0.001) and larger metastatic diameter (P<0.001). TM elevation was not associated with the N stage, primary site and microsatellite instability status (MSI) status, or the objective response rate and disease control rate after first‑line treatment. Having multiple TM elevations was associated with poorer progression‑free survival (PFS). With regard to non‑MSI‑H/deficient mismatch repair (dMMR) [immune checkpoint inhibitor (ICI) + tyrosine kinase inhibitor (TKI)] therapy, the single TM elevation dMMR patient group receiving third‑line ICI + TKI benefited the most, regardless of tumor burden, especially those with a neutrophil‑to‑lymphocyte ratio (NLR) <3. In conclusion, multiple TM elevations were associated with the T stage, poor differentiation, later clinical staging, metastatic site, tumor burden and worse PFS. Non‑MSI‑H/dMMR patients with single TM elevations benefited most from ICI + TKI therapy, particularly those with an NLR <3.

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1	Rawla P and Barsouk A, Hadjinicolaou AV and Barsouk A: Immunotherapies and targeted therapies in the treatment of metastatic colorectal cancer. Med Sci (Basel). 7:832019.PubMed/NCBI
2	Morris VK, Kennedy EB, Baxter NN, Benson AB III, Cercek A, Cho M, Ciombor KK, Cremolini C, Davis A, Deming DA, et al: Treatment of metastatic colorectal cancer: ASCO Guideline. J Clin Oncol. 41:678–700. 2023. View Article : Google Scholar : PubMed/NCBI
3	Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, Tian X, Guan X, Cen X and Zhao Y: Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther. 9:1322024. View Article : Google Scholar : PubMed/NCBI
4	Zhang C, Qin C, Dewanjee S, Bhattacharya H, Chakraborty P, Jha NK, Gangopadhyay M, Jha SK and Liu Q: Tumor-derived small extracellular vesicles in cancer invasion and metastasis: Molecular mechanisms, and clinical significance. Mol Cancer. 23:182024. View Article : Google Scholar : PubMed/NCBI
5	Cao Y and Wang X: Effects of molecular markers on the treatment decision and prognosis of colorectal cancer: A narrative review. J Gastrointest Oncol. 12:1191–1196. 2021. View Article : Google Scholar : PubMed/NCBI
6	Lorenzi M, Amonkar M, Zhang J, Mehta S and Liaw KL: Epidemiology of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) in solid tumors: A structured literature review. J Oncol. 2020:18079292020. View Article : Google Scholar
7	Schrock AB, Ouyang C, Sandhu J, Sokol E, Jin D, Ross JS, Miller VA, Lim D, Amanam I, Chao J, et al: Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer. Ann Oncol. 30:1096–1103. 2019. View Article : Google Scholar : PubMed/NCBI
8	Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, Bariani GM, De Jesus Acosta A, Doi T, Longo F, et al: Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: Updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 33:929–938. 2022. View Article : Google Scholar : PubMed/NCBI
9	Azam F, Latif MF, Farooq A, Tirmazy SH, AlShahrani S, Bashir S and Bukhari N: Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by oncology healthcare professionals. Case Rep Oncol. 12:728–736. 2019. View Article : Google Scholar : PubMed/NCBI
10	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
11	Masuishi T, Kuboki Y, Terazawa T, Nakamura M, Watanabe J, Ojima H, Makiyama A, Kotaka M, Hara H, Ohta T, et al: Exploratory analysis of baseline tumor burden in the TRUSTY study: A randomized phase 2/3 study of trifluridine/tipiracil plus bevacizumab versus irinotecan and fluoropyrimidine plus bevacizumab as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 40 (4_suppl):S872022. View Article : Google Scholar
12	Hoshino S, Takeuchi M, Kawakubo H, Matsuda S, Mayanagi S, Irino T, Fukuda K, Nakamura R, Wada N and Kitagawa Y: Usefulness of Neutrophil to Lymphocyte ratio at recurrence for predicting long-term outcomes in patients with recurrent esophageal squamous cell carcinoma. Ann Surg Oncol. 28:3001–3008. 2021. View Article : Google Scholar : PubMed/NCBI
13	Wang GY, Yang Y, Li H, Zhang J, Jiang N, Li MR, Zhu HB, Zhang Q and Chen GH: A scoring model based on neutrophil to lymphocyte ratio predicts recurrence of HBV-associated hepatocellular carcinoma after liver transplantation. PLoS One. 6:e252952011. View Article : Google Scholar : PubMed/NCBI
14	Ogino S and Goel A: Molecular classification and correlates in colorectal cancer. J Mol Diagn. 10:13–27. 2008. View Article : Google Scholar : PubMed/NCBI
15	Grady WM and Carethers JM: Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 135:1079–1099. 2008. View Article : Google Scholar : PubMed/NCBI
16	Abolghasemi Fard A and Mahmoodzadeh A: Unraveling the progression of colon cancer pathogenesis through epigenetic alterations and genetic pathways. Cureus. 16:e595032024.PubMed/NCBI
17	Keum N and Giovannucci E: Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 16:713–732. 2019. View Article : Google Scholar : PubMed/NCBI
18	Roshandel G, Ghasemi-Kebria F and Malekzadeh R: Colorectal cancer: Epidemiology, risk factors, and prevention. Cancers (Basel). 16:15302024. View Article : Google Scholar : PubMed/NCBI
19	Malki A, ElRuz RA, Gupta I, Allouch A, Vranic S and Al Moustafa AE: Molecular mechanisms of colon cancer progression and metastasis: Recent insights and advancements. Int J Mol Sci. 22:1302021. View Article : Google Scholar
20	Gao Y, Wang J, Zhou Y, Sheng S, Qian SY and Huo X: Evaluation of Serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 8:27322018. View Article : Google Scholar : PubMed/NCBI
21	Lech G, Słotwiński R, Słodkowski M and Krasnodębski IW: Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances. World J Gastroenterol. 22:1745–1755. 2016. View Article : Google Scholar : PubMed/NCBI
22	Yang AP, Liu J, Lei HY, Zhang QW, Zhao L and Yang GH: CA72-4 combined with CEA, CA125 and CAl9-9 improves the sensitivity for the early diagnosis of gastric cancer. Clin Chim Acta. 437:183–186. 2014. View Article : Google Scholar : PubMed/NCBI
23	Lakemeyer L, Sander S, Wittau M, Henne-Bruns D, Kornmann M and Lemke J: Diagnostic and prognostic value of CEA and CA19-9 in colorectal cancer. Diseases. 9:212021. View Article : Google Scholar : PubMed/NCBI
24	Shan Q, Fan Y, Guo J, Han X, Wang H and Wang Z: Relationship between tumor size and metastatic site in patients with stage IV non-small cell lung cancer: A large SEER-based study. PeerJ. 7:e78222019. View Article : Google Scholar : PubMed/NCBI
25	Zeng WG, Liang JW, Wang Z, Zhang XM, Hu JJ, Hou HR, Zhou HT and Zhou ZX: Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Chin J Cancer. 34:468–474. 2015. View Article : Google Scholar : PubMed/NCBI
26	Li C, Zhao K, Zhang D, Pang X, Pu H, Lei M, Fan B, Lv J, You D, Li Z and Zhang T: Prediction models of colorectal cancer prognosis incorporating perioperative longitudinal serum tumor markers: A retrospective longitudinal cohort study. BMC Med. 21:632023. View Article : Google Scholar : PubMed/NCBI
27	Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al: PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 372:2509–2520. 2015. View Article : Google Scholar : PubMed/NCBI
28	Le DT, Uram JN, Wang H, Bartlett B, Kemberling H, Eyring A, Saba Azad N, Donehower RC, Crocenzi TS, Goldberg RM, et al: Programmed death-1 blockade in mismatch repair deficient colorectal cancer. J Clin Oncol. 34 (15_suppl):S1032016. View Article : Google Scholar
29	Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, et al: Durable clinical benefit with Nivolumab Plus Ipilimumab in DNA mismatch Repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 36:773–779. 2018. View Article : Google Scholar : PubMed/NCBI
30	Haram A, Boland MR, Kelly ME, Bolger JC, Waldron RM and Kerin MJ: The prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer: A systematic review. J Surg Oncol. 115:470–479. 2017. View Article : Google Scholar : PubMed/NCBI
31	Kim JH, Lee JH, Lee HS, Shin SJ, Park EJ, Cho ES, Baik SH, Lee KY and Kang J: Elevated Neutrophil-to-lymphocyte ratio in perioperative periods is suggestive of poor prognosis in patients with colorectal cancer. J Inflamm Res. 14:4457–4466. 2021. View Article : Google Scholar : PubMed/NCBI