Tissue biopsy is the gold standard for diagnosis and morphological and immunohistochemical analyses to characterize cancer. However, tissue biopsy usually requires an invasive procedure, and it can be challenging depending on the condition of the patient and the location of the tumor. Even liquid biopsy analysis of body fluids such as blood, saliva, gastric juice, sweat, tears and cerebrospinal fluid may require invasive procedures to obtain samples. Liquid biopsy can be applied to circulating tumor cells (CTCs) or nucleic acids (NAs) in blood. Recently, urine has gained popularity due to its less invasive sampling, ability to easily repeat samples, and ability to follow tumor evolution in real-time, making it a powerful tool for diagnosis and treatment monitoring in cancer patients. With the development and advancements in extraction methods of urinary substances, urinary NAs have been found to be closely related to carcinogenesis, metastasis, and therapeutic response, not only in urological cancers but also in non-urological cancers. This review mainly highlights the components of urine liquid biopsy and their utility and limitations in oncology, especially in non-urological cancers.

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The generation of pathologic, immature, and dysfunctional vessels by angiogenesis is a mechanism of metastasis that has been a therapeutic target for colorectal cancer (CRC). In this study, we investigated the clinical relevance of intra-tumoral microvascular endothelial (mvE) cells in CRC using the xCell algorithm on transcriptome. A total of 1244 CRC patients in discovery and validation cohorts were analyzed. We found that an abundance of mvE cells did not mirror angiogenesis but reflected mature blood vessels because it was significantly associated with a high expression of vascular stability-related genes, including sphingosine-1-phosphate receptor genes and pericytes. Epithelial–mesenchymal transition and myogenesis gene sets were enriched in mvE cell abundant CRC, while mvE cell-less CRC enriched cell proliferation, oxidative phosphorylation, and protein secretion gene sets. mvE cell abundant CRC was associated with infiltration of M2 macrophages, dendritic cells, and less gamma-delta T cells (all p < 0.001), but not with the interferon-γ response. mvE cell abundant CRC was significantly associated with worse patient survival in CRC. Interestingly, mvE cell abundant CRC was significantly associated with a high response rate to chemotherapy (p = 0.012) and worse patient survival for those that did not receive chemotherapy. However, there was no survival difference in patients who underwent chemotherapy. In conclusion, we estimated the abundance of mvE cells using the xCell algorithm on tumor transcriptome finding its association with the number of mature blood vessels in a tumor microenvironment and its ability to predict response to chemotherapy, thereby patient survival in CRC.

Public Health 3.0 calls for the inclusion of new partners and novel data to bring systemic change to the US public health landscape. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has illuminated significant data gaps influenced by ongoing colonial legacies of racism and erasure. American Indian and Alaska Native (AI/AN) populations and communities have been disproportionately affected by incomplete public health data and by the COVID-19 pandemic itself. Our findings indicate that only 26 US states were able to calculate COVID-19‒related death rates for AI/AN populations. Given that 37 states have Indian Health Service locations, we argue that public health researchers and practitioners should have a far larger data set of aggregated public health information on AI/AN populations. Despite enormous obstacles, local Tribal facilities have created effective community responses to COVID-19 testing, tracking, and vaccine administration. Their knowledge can lead the way to a healthier nation. Federal and state governments and health agencies must learn to responsibly support Tribal efforts, collect data from AI/AN persons in partnership with Indian Health Service and Tribal governments, and communicate effectively with Tribal authorities to ensure Indigenous data sovereignty. (Am J Public Health. 2021;111(S3): S208–S214. https://doi.org/10.2105/AJPH.2021.306415 )

In experimental settings, maternal embryonic leucine zipper kinase (MELK), an apical member of the snf1/AMPK serine-threonine kinases family, is highly expressed in several malignancies, and plays a role in cell cycle and proliferation in cell culture settings. However, there is no clear insight on the underlying mechanism or association of MELK expression with several key players in the tumor microenvironment (TME) in regulating cancer progression and response to several drugs in the human tumor. We investigated the clinical relevance of MELK expression by performing silico analyses of 7,135 breast cancer patients using multiple independent large cohorts in this study. We found that MELK expression was significantly correlated with tumor growth assessed by American Joint Committee Cancer (AJCC) stage (p &lt; 0.001), Nottingham histological grade (both p &lt; 0.001), MKI67 expression (spearman rank correlation (r) = 0.704 and 0.888, respectively, both p &lt; 0.001), triple-negative breast cancer (TNBC) subtype (both p &lt; 0.001) and also with cell proliferation-related gene sets (all normalized enrichment score (NES) &gt; 1.70, all false discovery rate (FDR) &lt; 0.01) using gene set enrichment analysis (GSEA), in two large cohorts METABRIC and GSE96058. Furthermore, we observed worse patient survival (both p &lt; 0.001), high mutation rate (all p &lt; 0.03), and enhanced cancer cell survival pathways, including MTORC1 signaling, DNA repair and unfolded protein response (all NES &gt; 1.50) in high MELK expression breast cancer. Additionally, breast cancer with high MELK expression was significantly enriched in immune-related gene sets, including allograft rejection, interferon (IFN)-α response and IFN-γ response (all NES &gt; 1.30). Furthermore, infiltration of anti-cancer immune cells (CD4+ memory T cells, T helper type1 cells, CD8+ T cells, M1 macrophages, gamma-delta T cells, and dendritic cells) and pro-cancer (T helper type 2 cells and regulatory T cells), calculated by xCell algorithm, was associated with high MELK expression. High immune cell killing activity (CYT) was also significantly associated with high MELK expression. Although MELK expression did not correlate with sensitivity of any drug tested in cell lines, high MELK was significantly associated with high pathological complete response (pCR) rate after neoadjuvant chemotherapy (NAC) not only in TNBC (area under the curve (AUC) = 0.78, 0.81, and 0.93, respectively), the aggressive breast cancer subtype known to be associated with around 30-40% pCR, but also in ER-positive plus HER2-negative breast cancer (AUC = 0.62, 0.75, and 0.80, respectively), a subtype of breast cancer where pCR rates are very low, in three cohorts GSE25066, GSE20194 and HESS cohorts. In conclusion, our study shows that high MELK expression is significantly associated with cell proliferation, immune cell infiltration, and higher incidence of response to NAC both in ER-positive/HER2-negative and TNBC. Citation Format: Masanori Oshi, Shipra Gandhi, Michelle R Huyser, Yoshihisa Tokumaru, Li Yan, Rongrong Wu, Akimitsu Yamada, Itaru Endo, Kazuaki Takabe. Melk expression is associated with immune cell infiltration and pathological compete response (pcr) after neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-17.