Abstract
BackgroundMKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC).MethodsOncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database.ResultsMKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways.ConclusionMKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.
Highlights
Liver hepatocellular carcinoma (LIHC), a frequently occurring liver cancer, affects 6/100,000 people every year and is a primary cause of cancer-associated mortality [1, 2]
Marker of proliferation Ki-67 (MKI67) expression was increased in bladder cancer, CNS and brain cancers, breast cancer (BC), head and neck cancer (HNC), colorectal cancer (CRC), oesophageal cancer (EC), cervical cancer, gastric cancer (GC), liver cancer, lung cancer (LC), lymphoma, ovarian cancer, pancreatic cancer, and sarcoma compared with noncarcinoma samples (Fig. 1a)
MKI67 levels increased within BRCA, BLCA, COAD, CHOL, HNSC, ESCA, KIRP, KIRC, KICH, LIHC, PRAD, LUSC, LUAD, STAD, READ, UCEC and THCA relative to noncarcinoma samples
Summary
Liver hepatocellular carcinoma (LIHC), a frequently occurring liver cancer, affects 6/100,000 people every year and is a primary cause of cancer-associated mortality [1, 2]. In this regard, it is necessary to elucidate the tumour-immune interaction phenotypes and identify new immune-associated therapeutic targets for liver cancers. Ki67 shows high expression within cancer cells and can be regarded as a prognostic prediction factor for cancer [13, 14]. Cancer cells show high MK167 protein expression, and the positive MKI67 rate (referred to as the labelling index) is related to the clinicopathological characteristics and survival of diverse cancers, such as LIHC [21]. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC)
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