Analysis of the Relationship between Pan-immune-inflammation Value and the Clinical Pathological Characteristics and Surgical Prognosis of Thyroid Cancer
Abstract
This study aimed to explore the relationship between the preoperative pan-immune-inflammation value (PIV) and the clinicopathological characteristics and surgical prognosis of thyroid cancer.
This retrospective cohort study included 165 patients with thyroid cancer who underwent surgery. The value and clinical applicability of PIV and other immune-inflammatory biomarkers in assessing disease-free survival (DFS) were compared based on the area under the receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA). Patients were divided into high and low PIV groups according to the optimal cutoff value to assess the correlation between PIV and pathological characteristics. The Kaplan-Meier method was used for DFS analysis, and a Cox proportional hazards model was used to analyze the factors affecting DFS.
The AUC of PIV for predicting DFS was higher than that of other immune-inflammatory biomarkers, and PIV demonstrated the highest clinical utility. Compared with the low PIV group, the high PIV group had a lower proportion of papillary thyroid carcinoma, a higher proportion of anaplastic thyroid carcinoma, and higher rates of stage III–IV disease, lymph node metastasis, maximum tumor diameter ≥2 cm, and multiple lesions. The DFS was significantly shorter in the high PIV group than in the low PIV group. After adjusting for confounding factors, a high PIV level was an independent risk factor for poor surgical outcomes.
In conclusion, preoperative PIV is associated with the pathological type of thyroid cancer, TNM stage, lymph node metastasis status, and maximum tumor diameter. Furthermore, a high PIV level can increase the risk of poor surgical outcomes.
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18. Nash SH, Lanier AP, Southworth MB. Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013. Thyroid. 2018;28(4):481-7.
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26. Severson JJ, Serracino HS, Mateescu V, Raeburn CD, McIntyre RC Jr, Sams SB, et al. PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer. Cancer Immunol Res. 2015;3(6):620-30.
27. Lin B, Du L, Li H, Zhu X, Cui L, Li X. Tumor-infiltrating lymphocytes: Warriors fight against tumors powerfully. Biomed Pharmacother. 2020;132:110873.
28. Lee SWL, Adriani G, Kamm RD, Gillrie MR. Models for Monocytic Cells in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1224:87-115.
29. Feng F, Zheng G, Wang Q, Liu S, Liu Z, Xu G, et al. Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer. BMC Gastroenterol. 2018;18(1):148.
30. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
31. Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670-90.
32. Shaul ME, Fridlender ZG. Neutrophils as active regulators of the immune system in the tumor microenvironment. J Leukoc Biol. 2017;102(2):343-49.
33. Wang K, Wang X, Song L. Unraveling the complex role of neutrophils in lymphoma: From pathogenesis to therapeutic approaches (Review). Mol Clin Oncol. 2024;21(5):85.
34. Agoston AT, Srivastava A, Zheng Y, Bueno R, Odze RD, Szallasi Z. Paraneoplastic thrombocytosis is associated with increased mortality and increased rate of lymph node metastasis in oesophageal adenocarcinoma. Pathology. 2017;49(5):471-5.
35. Zhou L, Zhang Z, Tian Y, Li Z, Liu Z, Zhu S. The critical role of platelet in cancer progression and metastasis. Eur J Med Res. 2023;28(1):385.
36. Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancers (Basel). 2022;14(11):2675.
37. Fucà G, Beninato T, Bini M, Mazzeo L, Di Guardo L, Cimminiello C, et al. The Pan-Immune-Inflammation Value in Patients with Metastatic Melanoma Receiving First-Line Therapy. Target Oncol. 2021;16(4):529-36.
38. Yekedüz E, Tural D, Ertürk İ, Karakaya S, Erol C, Ercelep Ö, et al. The relationship between pan-immune-inflammation value and survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab in the second line and beyond: a Turkish oncology group kidney cancer consortium (TKCC) study. J Cancer Res Clin Oncol. 2022;148(12):3537-46.
39. Lin F, Zhang LP, Xie SY, Huang HY, Chen XY, Jiang TC, et al. Pan-Immune-Inflammation Value: A New Prognostic Index in Operative Breast Cancer. Front Oncol. 2022;12:830138.
40. Li YY, Li SJ, Liu MC, Chen Z, Li L, Shen F, et al. B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer. J Endocrinol Invest. 2023;46(11):2247-56.
41. Xie Z, Li X, He Y, Wu S, Wang S, Sun J, et al. Immune Cell Confrontation in the Papillary Thyroid Carcinoma Microenvironment. Front Endocrinol (Lausanne). 2020;11:570604.
2. Pizzato M, Li M, Vignat J, Laversanne M, Singh D, La Vecchia C, et al. The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020. Lancet Diabetes Endocrinol. 2022;10(4):264-272.
3. Araque KA, Gubbi S, Klubo-Gwiezdzinska J. Updates on the Management of Thyroid Cancer. Horm Metab Res. 2020;52(8):562-77.
4. Xue Y, Li J, Lu X. A Novel Immune-Related Prognostic Signature for Thyroid Carcinoma. Technol Cancer Res Treat. 2020;19:1533033820935860.
5. Zhang J, Sun P. Identification of GJC1 as a novel diagnostic marker for papillary thyroid carcinoma using weighted gene co-expression network analysis and machine learning algorithm. Discov Oncol. 2025;16(1):339.
6. Chang W, Chang Q, Lu H, Liu S, Li Y, Chen C. MicroRNA-873-5p suppresses cell malignant behaviors of thyroid cancer via targeting CXCL5 and regulating P53 pathway. Hum Vaccin Immunother. 2022;18(5):2065837.
7. Maiorino L, Daßler-Plenker J, Sun L, Egeblad M. Innate Immunity and Cancer Pathophysiology. Annu Rev Pathol. 2022;17:425-57.
8. Winarno GNA, Mulyantari AI, Kurniadi A, Suardi D, Zulvayanti Z, Trianasari N. Predicting Chemotherapy Resistance in Gestational Trophoblastic Neoplasia: Ratio of Neutrophils, Lymphocytes, Monocytes, and Platelets. Med Sci Monit. 2022;28:e938499.
9. Portale G, Bartolotta P, Azzolina D, Gregori D, Fiscon V. Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis. Langenbecks Arch Surg. 2023;408(1):85.
10. Zhang H, Shang X, Ren P, Gong L, Ahmed A, Ma Z, et al. The predictive value of a preoperative systemic immune-inflammation index and prognostic nutritional index in patients with esophageal squamous cell carcinoma. J Cell Physiol. 2019;234(2):1794-802.
11. Susok L, Said S, Reinert D, Mansour R, Scheel CH, Becker JC, et al. The pan-immune-inflammation value and systemic immune-inflammation index in advanced melanoma patients under immunotherapy. J Cancer Res Clin Oncol. 2022;148(11):3103-08.
12. Chen X, Hong X, Chen G, Xue J, Huang J, Wang F, et al. The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor. Transl Oncol. 2022;17:101338.
13. Yazgan SC, Yekedüz E, Utkan G, Ürün Y. Prognostic role of pan-immune-inflammation value in patients with metastatic castration-resistant prostate cancer treated with androgen receptor-signaling inhibitors. Prostate. 2022;82(15):1456-61.
14. Li F, Wang Y, Dou H, Chen X, Wang J, Xiao M. Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy. Front Oncol. 2024;14:1349021.
15. Barrea L, Gallo M, Ruggeri RM, Giacinto PD, Sesti F, Prinzi N, et al. Nutritional status and follicular-derived thyroid cancer: An update. Crit Rev Food Sci Nutr. 2021;61(1):25-9.
16. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 2013;13(3):184-99.
17. Liu J, Xu T, Ma L, Chang W. Signal Pathway of Estrogen and Estrogen Receptor in the Development of Thyroid Cancer. Front Oncol. 2021;11:593479.
18. Nash SH, Lanier AP, Southworth MB. Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013. Thyroid. 2018;28(4):481-7.
19. ZHANG ZY, HE HJ, SHAN GL, LIN YS. Research progress in epidemiology and risk factors of thyroid cancer. China Oncology. 2025;35(1):21-9.
20. Chen F, WU K, XU M, Yang Y. Meta-analysis of risk factors of thyroid cancer: base on case-control study. Chinese Journal of Endemiology. 2017:250-6.
21. Xu J, Zhang R, Peng Q, Jia Z, Xiao S, Sun N, et al. The profile and prognostic value of circulating lymphocyte subsets in metastatic colon cancer. Int Immunopharmacol. 2023;117:109848.
22. Shi ZY, Zhang SX, Li CH, Fan D, Xue Y, Cheng ZH, et al. Differential distribution and prognostic value of CD4+ T cell subsets before and after radioactive iodine therapy in differentiated thyroid cancer with varied curative outcomes. Front Immunol. 2022;13:966550.
23. Sun JC, Beilke JN, Lanier LL. Adaptive immune features of natural killer cells. Nature. 2009;457(7229):557-61.
24. Ao M, Li P, Sun D, Li X, Xu S, Hao Y. Changes in T lymphocyte subsets in peripheral blood of patients with middle-advanced cervical cancer before and after nimotuzumab combined with concurrent chemoradiotherapy. J Obstet Gynaecol. 2023;43(1):2179915.
25. Cunha LL, Marcello MA, Nonogaki S, Morari EC, Soares FA, Vassallo J, et al. CD8+ tumour-infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer. Clin Endocrinol (Oxf). 2015;83(2):246-53.
26. Severson JJ, Serracino HS, Mateescu V, Raeburn CD, McIntyre RC Jr, Sams SB, et al. PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer. Cancer Immunol Res. 2015;3(6):620-30.
27. Lin B, Du L, Li H, Zhu X, Cui L, Li X. Tumor-infiltrating lymphocytes: Warriors fight against tumors powerfully. Biomed Pharmacother. 2020;132:110873.
28. Lee SWL, Adriani G, Kamm RD, Gillrie MR. Models for Monocytic Cells in the Tumor Microenvironment. Adv Exp Med Biol. 2020;1224:87-115.
29. Feng F, Zheng G, Wang Q, Liu S, Liu Z, Xu G, et al. Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer. BMC Gastroenterol. 2018;18(1):148.
30. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
31. Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670-90.
32. Shaul ME, Fridlender ZG. Neutrophils as active regulators of the immune system in the tumor microenvironment. J Leukoc Biol. 2017;102(2):343-49.
33. Wang K, Wang X, Song L. Unraveling the complex role of neutrophils in lymphoma: From pathogenesis to therapeutic approaches (Review). Mol Clin Oncol. 2024;21(5):85.
34. Agoston AT, Srivastava A, Zheng Y, Bueno R, Odze RD, Szallasi Z. Paraneoplastic thrombocytosis is associated with increased mortality and increased rate of lymph node metastasis in oesophageal adenocarcinoma. Pathology. 2017;49(5):471-5.
35. Zhou L, Zhang Z, Tian Y, Li Z, Liu Z, Zhu S. The critical role of platelet in cancer progression and metastasis. Eur J Med Res. 2023;28(1):385.
36. Guven DC, Sahin TK, Erul E, Kilickap S, Gambichler T, Aksoy S. The Association between the Pan-Immune-Inflammation Value and Cancer Prognosis: A Systematic Review and Meta-Analysis. Cancers (Basel). 2022;14(11):2675.
37. Fucà G, Beninato T, Bini M, Mazzeo L, Di Guardo L, Cimminiello C, et al. The Pan-Immune-Inflammation Value in Patients with Metastatic Melanoma Receiving First-Line Therapy. Target Oncol. 2021;16(4):529-36.
38. Yekedüz E, Tural D, Ertürk İ, Karakaya S, Erol C, Ercelep Ö, et al. The relationship between pan-immune-inflammation value and survival outcomes in patients with metastatic renal cell carcinoma treated with nivolumab in the second line and beyond: a Turkish oncology group kidney cancer consortium (TKCC) study. J Cancer Res Clin Oncol. 2022;148(12):3537-46.
39. Lin F, Zhang LP, Xie SY, Huang HY, Chen XY, Jiang TC, et al. Pan-Immune-Inflammation Value: A New Prognostic Index in Operative Breast Cancer. Front Oncol. 2022;12:830138.
40. Li YY, Li SJ, Liu MC, Chen Z, Li L, Shen F, et al. B cells and tertiary lymphoid structures are associated with survival in papillary thyroid cancer. J Endocrinol Invest. 2023;46(11):2247-56.
41. Xie Z, Li X, He Y, Wu S, Wang S, Sun J, et al. Immune Cell Confrontation in the Papillary Thyroid Carcinoma Microenvironment. Front Endocrinol (Lausanne). 2020;11:570604.
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How to Cite
1.
Liang W, Fu D. Analysis of the Relationship between Pan-immune-inflammation Value and the Clinical Pathological Characteristics and Surgical Prognosis of Thyroid Cancer. Iran J Allergy Asthma Immunol. 2025;:1-12.
