Plasma Exosome Gene Signature Differentiates Colon Cancer from Healthy Controls.

BACKGROUND: Liquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors. In this initial feasibility analysis, we identified an exosome gene signature of 445 genes (ExoSig445) from colon cancer patients, including those with PC, that is distinct from healthy controls. METHODS: Plasma exosomes from 42 patients with metastatic and non-metastatic colon cancer and 10 healthy controls were isolated and verified. RNAseq analysis of exosomal RNA was performed and differentially expressed genes (DEGs) were identified by the DESeq2 algorithm. The ability of RNA transcripts to discriminate control and cancer cases was assessed by principal component analysis (PCA) and Bayesian compound covariate predictor classification. An exosomal gene signature was compared with tumor expression profiles of The Cancer Genome Atlas. RESULTS: Unsupervised PCA using exosomal genes with greatest expression variance showed stark separation between controls and patient samples. Using separate training and test sets, gene classifiers were constructed capable of discriminating control and patient samples with 100% accuracy. Using a stringent statistical threshold, 445 DEGs fully delineated control from cancer samples. Furthermore, 58 of these exosomal DEGs were found to be overexpressed in colon tumors. CONCLUSIONS: Plasma exosomal RNAs can robustly discriminate colon cancer patients, including patients with PC, from healthy controls. ExoSig445 can potentially be developed as a highly sensitive liquid biopsy test in colon cancer.

Exosomes as a Source of Biomarkers for Gastrointestinal Cancers.

Exosomes are small, lipid-bilayer bound extracellular vesicles of 40-160 nanometers in size that carry important information for intercellular communication. Exosomes are produced more by tumor cells than normal cells and carry tumor-specific content, such as DNA, RNA, and proteins, which have been implicated in tumorigenesis, tumor progression, and treatment response. Due to the critical role of exosomes in cancer development and progression, they can be exploited to develop specific biomarkers and therapeutic targets. Since exosomes are present in various biofluids, such as blood, saliva, urine, and peritoneal fluid, they are ideally suited to be developed as liquid biopsy tools for early diagnosis, molecular profiling, disease surveillance, and treatment response monitoring. In the past decade, numerous studies have been published about the functional significance of exosomes in a wide variety of cancers, with a particular focus on exosome-derived RNAs and proteins as biomarkers. In this review, utilizing human studies on exosomes, we highlight their potential as diagnostic, prognostic, and predictive biomarkers in gastrointestinal cancers.

The role of cytoreductive surgery and intraperitoneal chemotherapy in gastric cancer.

Gastric cancer (GC) with peritoneal carcinomatosis (PC) progresses rapidly and has historically dismal survival rates. Given the aggressive tumor biology and poor survival outcomes of patients with GC/PC, additional treatments beyond systemic chemotherapy are needed. Cytoreductive surgery and intraperitoneal chemotherapy have been effective management options for peritoneal surface malignancies, with increasing data to support their use in GC/PC. This review highlights the evolution of the surgical treatment of GC/PC, and discusses critical studies supporting the role of cytoreductive surgery, appropriate patient selection, and various methods in the delivery of intraperitoneal chemotherapy for patients with GC/PC.

Quantitative assessment of hand motor function in cervical spinal disorder patients using target tracking tests.

Cervical spondylotic myelopathy (CSM) is a chronic spinal disorder in the neck region. Its prevalence is growing rapidly in developed nations, creating a need for an objective assessment tool. This article introduces a system for quantifying hand motor function using a handgrip device and target tracking test. In those with CSM, hand motor impairment often interferes with essential daily activities. The analytic method applied machine learning techniques to investigate the efficacy of the system in (1) detecting the presence of impairments in hand motor function, (2) estimating the perceived motor deficits of CSM patients using the Oswestry Disability Index (ODI), and (3) detecting changes in physical condition after surgery, all of which were performed while ensuring test-retest reliability. The results based on a pilot data set collected from 30 patients with CSM and 30 nondisabled control subjects produced a c-statistic of 0.89 for the detection of impairments, Pearson r of 0.76 with p < 0.001 for the estimation of ODI, and a c-statistic of 0.82 for responsiveness. These results validate the use of the presented system as a means to provide objective and accurate assessment of the level of impairment and surgical outcomes.

Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study.

BACKGROUND: The current methods of assessing motor function rely primarily on the clinician's judgment of the patient's physical examination and the patient's self-administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand. METHODS: Eleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients' adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either "functional" or "nonfunctional" in order to validate the system's responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated. RESULTS: The control participants had lower MediSens MAE scores of 8.09%±1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%±6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%±1.60%, while the nonfunctional CSM patients had an average score of 12.41%±6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14×10⁻5). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04). CONCLUSIONS: The MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand.