A prognostic stemness biomarker CCDC80 reveals acquired drug resistance and immune infiltration in colorectal cancer

Abstract

To the Editor, Colorectal cancer (CRC) is a malignance ranking the third cause of death in malignant tumors. 1 The high mortality of CRC is mainly caused by frequent postoperative metastasis and multidrug resistance. 2 A group of cancer stem cells (CSCs) have been discovered in CRC and the mRNA expression-based stemness index (mRNAsi) was considered as a novel indicator to measure cancer development and drug resistance. 3,4 In the present study, we first explored the prognosis of mRNAsi in CRC patients and identified the critical genes related to immune infiltration and drug resistance. The mRNAsi was much lower in normal samples than that in CRC tissues (P value = 7.458 × 10 −18) and indicated a favorable prognosis in patients with CRC (P = .016), which was inconsistent with our general understanding in other type of cancers (Figure 1A and B). 5-7 In addition, the mRNAsi had no relationship with clinical characteristics, including age, gender, tumor, node, metastasis (TNM) stage, and grade (Figure S1A). To explore the unique characteristic of mRNAsi in CRC, we performed the weighted gene co-expression network analysis of 6501 differentially expressed genes and identified 17 modules (Figure 1C and Figure S1B and C). Among them, the brown, green, and yellow modules showed significant relationship with mRNAsi with correlation index −0.71 (P = 4 × 10 −55), −0.71 (P = 8 × 10 −57), and 0.71 (P = 1 × 10 −55), respectively (Figure 1D). In total, 193 critical genes related to mRNAsi (135 genes in brown, 48 genes in green, and 10 genes in yellow) were filtrated (Figure 1E, Table S1). We found 24 key genes were significant closely associated with poor prognosis in CRC by univariate analysis (Figure 1F, Table S2). Causal relationship with proteins were analyzed by DisNor and indicated that these genes were closely connected and associated with adipogenesis (Figure 1G). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Downregulation of the Coiled-Coil Domain Containing 80 and Its Perspective Mechanisms in Ovarian Carcinoma: A Comprehensive Study

“…The clinical significance of CCDC80 in malignant tumors was attractive. In previous studies, CCDC80 was reported as a prognostic signature in serous ovarian carcinoma, colorectal cancer, and muscle-invasive bladder cancer [26][27][28]. However, no study has revealed the discriminatory capacity of CCDC80 in malignant tumors.…”

CDK12 orchestrates super‐enhancer‐associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer

“…47,48 For example, CCDC80 is the core regulator for self-renew in haematopoietic stem/progenitor cell, 47 which functions as a stemness biomarker in CRC. 48 In addition, Yang et al 49 have reported that CCDC25 enhances metastasis via activation of the ILK-β-parvin pathway in tumour cells. Therefore, it is conceivable that CCDC137 might promote proliferation, CSC characteristics and metastasis in CRC.…”

The Value of the Stemness Index in Ovarian Cancer Prognosis

“…Zhao et al verified that high levels of MFAP4 expression predict platinum-based chemotherapy resistance and imply a poor prognosis in patients with serous OC [ 45 ]. CCDC80 is a common tumor stemness marker used in a variety of solid tumor prognostic models [ 46 , 47 , 48 ]. Studies have shown that it helps tumor cells acquire drug resistance and immune infiltration [ 46 ].…”

“…CCDC80 is a common tumor stemness marker used in a variety of solid tumor prognostic models [ 46 , 47 , 48 ]. Studies have shown that it helps tumor cells acquire drug resistance and immune infiltration [ 46 ]. USP1 is one cause of drug resistance in tumors, allowing them to evade chemotherapy by modulating the p38 pathway and activating the MAPK pathway [ 49 , 50 ].…”