Purpose: Tumor metastasis continues to be the major obstacle to cancer therapy and the leading cause of cancer-related death. Methods used to detect metastasis, especially occult metastases, have received a great deal attention. In this study, a novel selective peptide was assessed for its specific binding to metastasis. Methods: The FliTrx bacterial peptide display system, an alternative to phage peptide display, was used to identify a 5-amino acid peptide termed TMTP1 (NVVRQ), which binds to the highly metastatic prostate cancer cell line PC-3M-1E8. The synthetic TMTP1 was tested in vitro for its binding specificity and affinity to highly metastatic cancer cells. The tumor targeting assays were done in vivo by i.v. injection of FITC-conjugated TMTP1into tumor-bearing mice. Results: TMTP1specifically bound to a series of highly metastatic tumor cells, including prostate cancer PC-3M-1E8, breast cancer MDA-MB-435S, lung cancer PG-BE1, and gastric cancer MKN-45sci, in vitro and in vivo but not to the poorly metastatic or nonmetastatic cell line, including prostate cancer PC-3M-2B4, breast cancer MCF-7, lung cancer PG-LH7, or murine fibroblast cell NIH/3T3. FITC-TMTP1strongly and specifically targeted the metastasis foci in tumor-bearing mice 24 h after i.v. peptide injection. Moreover, the occult metastases were specifically detected by FITC-TMTP1. Conclusion: Our results suggest that TMTP1is a potential strategy for the development of new diagnostic tracers or alternative anticancer agents for tumor metastasis.Metastasis is responsible for most therapeutic failures in cancer treatment and leads to death in most cancer patients. Once cancer is diagnosed, it is important to know whether the disease is confined to the primary site or has spread either regionally or systemically (1). At initial diagnosis, approximately 70% of cancer patients can be cured surgical removal of tumors. Adjuvant radiation therapy and/or chemotherapy are beneficial for cancer patients postoperation (2 -5). However, a proportion of patients with no evident systemic dissemination will develop recurrent disease or metastasis after ''curative'' therapy (6, 7). In these cases, the cancer has clearly undergone occult systemic spread and is undetectable by routine methods including careful clinical, pathologic, biochemical, and radiologic evaluation. Sometimes, the metastatic cancer cells form microfoci (<2 mm) and maintain a balance between proliferation and apoptosis without evoking clinical symptoms (8 -11). Evasion of the host immune system by these tumor cells leads to systemic spread to tissues and eventually ruin the host (5, 12 -14). The 5-year survival rate in patients with recurrence or metastasis is <50% (15,16). Although many new treatment modalities have been developed, they seldom improve the survival rate of patients with cancer metastasis (17 -20).Diagnostic approaches for micrometastasis are essential to controlling metastasis. Heterogeneous tumor cells can be divided into clones with highly or poorly metastatic potent...

Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes. We detected four modules related to one or more clinical features significantly shared across all modeling datasets, and identified one stage-associated module and one grade-associated module. Our analysis showed that MMP2, COL3A1, COL1A2, FBN1, COL5A1, COL5A2, and AEBP1 are top hub genes related to stage, while CDK1, BUB1, BUB1B, BIRC5, AURKB, CENPA, and CDC20 are top hub genes related to grade. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggest that extracellular matrix interactions and mitotic signaling pathways are crucial determinants of tumor stage and grade. The relationships between gene expression modules and tumor stage or grade were validated in five independent datasets. These results could potentially be developed into a more objective scoring system to improve prediction of SOC outcomes.

PurposeTo evaluate the value of C1QC+ and SPP1+ TAMs gene signatures in patients with cervical cancer.MethodsWe compare the C1QC+ and SPP1+ TAMs gene signatures with the M1/M2 gene signatures at single cell level and bulk RNA-seq level and evaluate which gene signature can clearly divide TAMs and patients with cervical cancer into distinct clinical subclusters better.ResultsAt single-cell level, C1QC+ and SPP1+ TAMs gene signatures, but not M1 and M2 gene signatures, could clearly divided TAMs into two subclusters in a colon cancer data set and an advanced basal cell data set. For cervical cancer data from TCGA, patients with C1QChigh and SPP1low TAMs gene signatures have the best prognosis, lowest proportion (34.21%) of locally advanced cervical cancer (LACC), and highest immune cell infiltration, whereas patients with C1QClow and SPP1high TAMs gene signatures have the worst prognosis, highest proportion (71.79%) of LACC and lowest immune cell infiltration. Patients with C1QChigh and SPP1low TAMs gene signature have higher expression of most of the Immune checkpoint molecules (ICMs) than patients with C1QClow and SPP1high TAMs gene signatures. The GSEA results suggested that subgroups of patients divided by C1QC+ and SPP1+ TAMs gene signatures showed different anti- or pro-tumor state.ConclusionC1QC+ and SPP1+ TAMs gene signatures, but not M1/M2 gene signatures, can divide cervical patients into subgroups with different prognosis, tumor stage, different immune cell infiltration, and ICMs expression. Our findings may help to find suitable treatment strategy for cervical cancer patients with different TAMs gene signatures.