Kinesin family member C1 (KIFC1) is a minus-end-directed motor protein that is critically involved in microtubule crosslinking and spindle formation. KIFC1 is essential for supernumerary centrosomes, and it is associated with the initiation and progression of cancers. In the present study, we initially reviewed the The Cancer Genome Atlas database and observed that KIFC1 is abundantly expressed in most types of tumors. We then analyzed the gene alteration profiles, protein expressions, prognoses, and immune reactivities of KIFC1 in more than 10,000 samples from several well-established databases. In addition, we conducted a gene set enrichment analysis to investigate the potential mechanisms for the roles of KIFC1 in carcinogenesis. The pan-cancer analysis of KIFC1 demonstrates significant statistical correlations of the KIFC1 expression with the clinical prognoses, the oncogenic signature gene sets, the myeloid-derived suppressor cell infiltration, the ImmunoScore, the immune checkpoints, the microsatellite instabilities, and the tumor mutational burdens across multiple tumors. These data may provide important information on the understanding of the role and mechanisms of KIFC1 in carcinogenesis and immunotherapy, as well as on the clinical progression of a variety of cancers.

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

The overexpression of the enzymes involved in the degradation of procollagen lysine is correlated with various tumor entities. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) expression was found to be correlated to the progression and migration of cancer cells in gastric, lung and prostate cancer. Here, we analyzed the gene expression, protein expression, and the clinical parameters of survival across 33 cancers based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC), function annotation of the mammalian genome 5 (FANTOM5), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases. Genetic alteration, immune infiltration and relevant cellular pathways were analyzed in detail. PLOD3 expression negatively correlated with survival periods and the infiltration level of CD8+ T cells, but positively correlated to the infiltration of cancer associated fibroblasts in diverse cancers. Immunohistochemistry in colon carcinomas, glioblastomas, and soft tissue sarcomas further confirm PLOD 3 expression in human cancer tissue. Moreover, amplification and mutation accounted for the largest proportion in esophageal adenocarcinoma and uterine corpus endometrial carcinoma, respectively; the copy number alteration of PLOD3 appeared in all cancers from TCGA; and molecular mechanisms further proved the effect of PLOD3 on tumorigenesis. In particular, PLOD3 expression appears to have a tumor immunological effect, and is related to multiple immune cells. Furthermore, it is also associated with tumor mutation burden and microsatellite instability in various tumors. PLOD3 acts as an inducer of various cancers, and it could be a potential biomarker for prognosis and targeted treatment.

Pituitary tumor-transforming gene 1 (PTTG1) encodes a multifunctional protein that is involved in many cellular processes. However, the potential role of PTTG1 in tumor formation and its prognostic function in human pan-cancer is still unknown. The analysis of gene alteration, PTTG1 expression, prognostic function, and PTTG1-related immune analysis in 33 types of tumors was performed based on various databases such as The Cancer Genome Atlas database, the Genotype-Tissue Expression database, and the Human Protein Atlas database. Additionally, PTTG1-related gene enrichment analysis was performed to investigate the potential relationship and possible molecular mechanisms between PTTG1 and tumors. Overexpression of PTTG1 may lead to tumor formation and poor prognosis in various tumors. Consequently, PTTG1 acts as a potential oncogene in most tumors. Additionally, PTTG1 is related to immune infiltration, immune checkpoints, tumor mutational burden, and microsatellite instability. Thus, PTTG1 could be potential biomarker for both prognosis and outcomes of tumor treatment and it could also be a promising target in tumor therapy.

Despite various treatment attempts, the heterogenous group of soft tissue sarcomata (STS) with more than 100 subtypes still shows poor outcomes. Therefore, effective biomarkers for prognosis prediction and personalized treatment are of high importance. The Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase (PLOD) gene family, which is related to multiple cancer entities, consists of three members which encode important enzymes for the formation of connective tissue. The relation to STS, however, has not yet been explored. In this study, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the role of PLOD1–3 in STS. It was found that an overexpression of PLOD family members correlates with poor prognosis, which might be due to an increased infiltration of immune-related cells in the tumor microenvironment. In STS, the expression of PLOD genes could be a novel biomarker for prognosis and a personalized, more aggressive treatment in these patients.