SOX9 Immunosuppression in Primary Colorectal Cancer Tumors with Lymph Node Metastasis
Journal: Advances in Medicine and Engineering Interdisciplinary Research DOI: 10.32629/ameir.v2i2.2191
Abstract
Introduction and aims: Colorectal cancer is the most frequent malignant tumor of the digestive system. Its pathogeny is complex and involves the APC/β-catenin sequence. Lymph node metastases are a significant indicator for determining treatment and are a prognostic factor. SOX9 overexpression is related to oncogenic qualities and the capacity for metastasis. Our aim was to analyze SOX9 immunoexpression in primary colorectal cancer and lymph node metastasis status. Material and methods: Seventy-nine available cases were divided into the group with lymph node metastasis (n = 38) and the group without lymph node metastasis (n = 41), evaluating their SOX9 expression. The IBM SPSS version 27 program in Spanish was utilized to carry out the statistical analysis, obtaining measures of central tendency, the kappa index, standard deviation, Wilcoxon Mann-Whitney nonparametric measurements, Spearman's correlation coefficient, and chi-square test and Student's t test values. SOX9 immunoexpression was evaluated through the mean-based H-score, with high immunoexpression as a score ≥ 145 and low immunoexpression as a score ≤ 144. Results: A p = 0.73 was obtained that was not statistically significant, regarding the relation of SOX9 expression in primary colorectal cancer to lymph node metastasis. Conclusions: The absence or presence of lymph node metastasis was independent from SOX9 immunoexpression in primary colorectal cancer. However, due to the limited size of the population analyzed, further research is needed.
Keywords
colorectal cancer; SOX9; immunoexpression; metastasis; lymph nodes
Funding
Funding was obtained from the Universidad Autónoma de San Luis Potosí (UASLP).
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[2] International Agency for Research on Cancer. Colorectal cancer. GLOBOCAN 2020 [Internet]. Lyon: IARC; 2022. 8-Colon-fact-sheet.pdf.
[3] Burgart LJ, Chopp WV, Jain D. Protocol for the examination of resection specimens from patients with primary carcinoma of the colon and rectum. Coll Am Pathol [Internet]. 2022. https://documents.cap.org/protocols/ColoRectal 4.2.0.2 .REL CAPCP.pdf?
[4] Jessup M, Goldberg RM, Asare EA, et al. Colon and Rectum. In: Amin MB, editor. AJCC Cancer Staging Manual. 8th ed New York: Springer; 2017. p. 251-74.
[5] Nguyen L, Goel A, Chung D. Pathways of colorectal carcinogenesis. Gastroenterology. 2020;158:291-302, http://dx.doi.org/10 .1053/j.gastro.2019.08.059
[6] Takamatsu M, Yamamoto N, Kawachi H, et al. Prediction of early colorectal cancer metastasis by machine learning using digital slide images. Comput Methods Programs Biomed. 2019;178:155-61, http://dx.doi.org/10.1016/j.cmpb. 2019.06.022.
[7] Ulintz PJ, Greenson JK, Fearon ER, et al. Lymph node metastases in colon cancer are polyclonal. Clin Cancer Res. 2018;24:2214-24, http://dx.doi.org/10.1158/1078- 0432.CCR-17-1425.
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[9] Johncilla M, Yantiss RK. Histology of colorectal carcinoma proven and purported prognostic factor. Surg Pathol Clin. 2020;13:503- 20, http://dx.doi.org/10.1016/j.path.2020 .05.008
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[11] Liang X, Duronio GN, Yaying Y, et al. An enhancer-driven stem cell-like program mediated by SOX9 blocks intestinal differentiation in colorectal cancer. Gastroenterology. 2022;162:209-22, http://dx.doi.org/10.1053/j.gastro.2021 .09.044
[12] Lü B, Fand Y, Xu J, et al. Analysis of SOX9 expression in colorectal cancer. Am J Clin Pathol. 2008;130:897-904, http://dx.doi.org/10.1309/AJCPW1W8GJBQGCNI
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[14] Zhou T, Wu L, Ma N, et al. SOX9-activated FARSAAS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9. Cell Death Dis. 2020;11:1071, http://dx.doi.org/10 .1038/s41419-020-03273-4.
[15] Xu Y, Zhang X, Hu X, et al. The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. Mol Med. 2018;24:52, http://dx.doi.org/10.1186/s10020-018-0050-5
[16] Qian Y, Xia S, Feng Z. SOX9 mediated transcriptional activation of FOXK2 is critical for colorectal cancer cells proliferation. Biochem Biophys Res Commun. 2017;483:475-81, http://dx.doi.org/10.1016/j.bbrc.2016.12.119
[17] Xia S, Yang Z, Qi X, et al. Overexpression of SOX9 and DNMT1 predicts poor prognosis and chemoresistance of colorectal cancer. Int J Clin Exp Pathol. 2016;9:589- 600, ijcep0020029.pdf.
[18] Xu C, Ding Y-H, Wang K, et al. Claudin-7 deficiency promotes stemness properties in colorectal cancer through SOX9-mediated Wnt/β-catenin signalling. J Transl Med. 2021;19:311, http://dx.doi.org/10.1186/s12967-021-02983-3
[19] Liang J, Liu Q, Xia L, et al. Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9. Cancer Sci. 2023;114:822-36, http://dx.doi.org/10.1111/cas.15652
[20] Miao D, Wang Y, Jia Y, et al. ZRANB1 enhances stemcell-like features and accelerates tumor progression by regulating SOX9-mediated USP22/Wnt/β-catenin pathway in colorectal cancer. Cell Signal. 2022;90:110200, http://dx.doi. org/10.1016/j.cellsig.2021.110200
[21] Carrasco-Garcia E, López L, Aldaz P, et al. SOX9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin. Sci Rep. 2016;6:32350, http://dx.doi.org/10.1038/srep32350
[22] Candy PA, Phillips MR, Redfern AD, et al. Notch-induced transcription factors are predictive of survival and 5-fluorouracil response in colorectal cancer patients. Br J Cancer 2013. 2013;109:1023-30, http://dx.doi.org/10.1038/bjc.2013.431
[23] Roche KC, Gracz AD, Liu XF, et al. SOX9 maintains reserve stem cells and preserves radio resistance in mouse small intestine. Gastroenterology. 2015;149:1553-63, http://dx.doi.org/10.1053/j.gastro.2015.07.004
[24] Fitzgibbons P, Connolloy J. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Coll Am Pathol [Internet]. https://www.cap.org/protocols-and-guidelines/cancer-reporting-tools/cancer-protocol templates
[25] Thabane L, Ma J, Chu R, et al. A tutorial on pilot studies: the what, why and how. BMC Med Res Methodol. 2010;10:1, http://dx.doi.org/10.1186/1471-2288-10-1
[26] Fernández P. Determinación del tamano muestral. Fisterra [Internet]. https://www.fisterra.com/formacion/metodologia-investigacion /determinacion-tamano-muestral/#sec2
[27] Hérnandez-Samperi R. Análisis de los datos en la ruta cuantitativa. In: Hernández- Samperi R, editor. Metodología de la investigación las rutas cuantitativa, cualitativa y mixta. Ciudad de México: Mc Graw Hill; 2018. p. 363-9.
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