Discovery, identification and mechanism of chemosensitivity-relate biomarker inter-α-trypsin inhibitor heavy chain 4 in metastatic colorectal cancer.

Predictive biomarkers of response to chemotherapy in patients with metastatic colorectal cancer (mCRC) are needed to better characterize tumors and enable more tailored therapies. Here we used serum proteomics to screen for chemotherapy predictive markers. We found that higher baseline serum inter-α-trypsin inhibitor Heavy Chain 4 (ITIH4) expression in newly diagnosed mCRC patients was associated with poorer response to standard first-line chemotherapy.

Genetic and microbial determinants of azoxymethane-induced colorectal tumor susceptibility in Collaborative Cross mice and their implication in human cancer.

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis.

Genetic architecture of the acute and persistent immune cell response after radiation exposure.

Hematologic toxicity is a common side effect of multimodal cancer therapy. Nearly all animal studies investigating the causes of radiotherapy-induced hematologic toxicity use inbred strains with limited genetic diversity and do not reflect the diverse responses observed in humans. We used the population-based Collaborative Cross (CC) mouse resource to investigate the genetic architecture of the acute and persistent immune response after radiation exposure by measuring 22 immune parameters in 1,720 CC mice representing 35 strains.

Primary Tumor Resection Plus Chemotherapy versus Chemotherapy Alone for Colorectal Cancer Patients with Synchronous Bone Metastasis.

: Colorectal cancer (CRC) bone metastasis (BM), particularly synchronous metastasis, is infrequent and has a poor prognosis. Radical surgery for CRC with BM is challenging, and chemotherapy is the standard treatment. However, it is unclear whether combining chemotherapy with primary tumor resection (PTR) yields greater survival benefits than chemotherapy alone, as no relevant reports exist.

Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial.

Background: Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC.

Sintilimab plus bevacizumab and CapeOx (BBCAPX) on first-line treatment in patients with RAS mutant, microsatellite stable, metastatic colorectal cancer: study protocol of a randomized, open-label, multicentric study.

Background: Rat sarcoma viral oncogene homolog (RAS) gene mutation is a common molecular event in colorectal cancer (CRC). The prognosis of mCRC (metastatic colorectal cancer) patients with RAS mutation is poor and capecitabine and oxaliplatin (CapeOx) plus bevacizumab has shown to be one of the standard therapeutic regimens as first line for these patients with objective response rate (ORR) of ~ 50% and median progression-free survival (mPFS) of 8-9 months. Immunotherapy, especially anti-programmed death 1 (PD-1) monoclonal antibody has demonstrated ground-breaking results in deficient mismatch repair (dMMR) / microsatellite instability-high (MSI-H) mCRC patients.

The Genomic and Proteomic Profiles of NTRK Genes and Trk Receptors in Liver Hepatocellular Carcinoma.

Background: The neurotrophic tyrosine kinase (NTRK) gene family includes NTRK1, NTRK2, and NTRK3, which encode tropomyosin receptor kinases TrkA, TrkB, and TrkC, respectively. This study aimed to initially assess the genomic and proteomic profiles of NTRK genes and Trk receptors in liver hepatocellular carcinoma (LIHC).

Methods: The ONCOMINE, UALCAN, GEPIA, cBioPortal, FusionGDB, SurvivalMeth, and the Human Protein Atlas databases were searched for NTRK gene expression and protein data in LIHC.

Expression and prognostic impact of NTF3 and TrkC in hepatocellular carcinoma.

Background: Treatment of patients with fusion-positive cancers using first-generation tropomyosin-related kinase (Trk) inhibitors is associated with high response rates, regardless of tumor histology. However, there have been few studies on neurotrophin-3 (NTF3) and TrkC ligands in hepatocellular carcinoma (HCC).

Methods: We used immunohistochemistry to evaluate NTF3 and TrkC expression levels in tissue samples.

Host genetics and gut microbiota cooperatively contribute to azoxymethane-induced acute toxicity in Collaborative Cross mice.

Azoxymethane (AOM) is a widely used carcinogen to study chemical-induced colorectal carcinogenesis and is an agent for studying fulminant hepatic failure. The inter-strain susceptibility to acute toxicity by AOM has been reported, but its association with host genetics or gut microbiota remains largely unexplored. Here a cohort of genetically diverse Collaborative Cross (CC) mice was used to assess the contribution of host genetics and the gut microbiome to AOM-induced acute toxicity.

Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness.

Background: Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown.

Correction to: Genetic and metabolic links between the murine microbiome and memory.

An amendment to this paper has been published and can be accessed via the original article.

Risk of Second Primary Cancers Among Long-Term Survivors of Breast Cancer.

The current study explored the risk of developing second primary cancers (SPCs) among long-term early-stage breast cancer survivors and identified risk factors to build an externally validated clinical prediction model. The cumulative incidence of SPCs was calculated by Gray method among survivors of early-stage initial primary breast cancer (IPBC). Comparisons of treatment-related risk by selected organ sites were performed.

A Competing Nomogram to Predict Survival Outcomes in Invasive Micropapillary Breast Cancer.

Although it is widely accepted that invasive micropapillary carcinoma (IMPC) presents more aggressive behavior and has a higher aggressive behavior, the prognosis of IMPC compared with invasive ductal carcinoma (IDC) remains controversial. We conducted this study to explore gene expression profiles of IMPC and establish a competing nomogram that predicts the survival outcomes across these two groups of patients. Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed.

Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death.

Purpose: Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups.

Methods: Surveillance, Epidemiology, and End Results databases were utilized to identify 181,108 breast cancer patients with > 5 years survival.

Zyxin as a potential cancer prognostic marker promotes the proliferation and metastasis of colorectal cancer cells.

Colorectal cancer (CRC) is a leading cause of cancer death. This study was conducted to investigate the functions and mechanisms of Zyxin (ZYX) in CRC. Multiomics analysis associated ZYX with CRC metastasis.

Identification of Kininogen 1 as a Serum Protein Marker of Colorectal Adenoma in Patients with a Family History of Colorectal Cancer.

The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.

Competing nomograms help in the selection of elderly patients with colon cancer for adjuvant chemotherapy.

Purpose: The extent to which ≥ 70 year patients with colon cancer benefit from adjuvant chemotherapy in the presence of competing risks remains controversial.

Methods: 18,937 patients ≥ 70 years with high-risk stage II and stage III colon cancer were retrospectively reviewed from SEER database. Propensity score matching (PSM) was used to adjust for potential baseline confounding.

A Novel and Reliable Method to Detect Microsatellite Instability in Colorectal Cancer by Next-Generation Sequencing.

Two types of molecular tests have been established to assess the deficiency of the DNA mismatch repair (MMR) system: microsatellite instability (MSI) and immunohistochemical (IHC) analysis. We have developed a reliable method to analyze the MSI status by next-generation sequencing (NGS) based on read-count distribution. A total of 91 patients with primary colorectal cancer were recruited.

Left-sided primary tumor is a favorable prognostic factor for metastatic colorectal cancer patients receiving surgery.

Objective: The role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer.

Materials And Methods: Information of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database.

Identification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach.

Colorectal cancer (CRC) is a common malignant neoplasm worldwide. It is important to identify new biomarkers for the early detection of CRC. In this study, magnetic beads and the Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) platform were used to analyse CRC and healthy control (HC) serum samples.

High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers.

Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integratingproteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa.

The clinicopathological features and prognostic factors of gastric squamous cell carcinoma.

Primary gastric squamous cell carcinoma (SCC) is an exceedingly rare disease. We increased the understanding of gastric SCC and evaluated prognostic factors of gastric SCC.In this large-population cohort study, we retrospectively collected 163 primary gastric SCC and 66,209 primary gastric adenocarcinoma cases from the surveillance, epidemiology, and end results program (SEER) database from 1988 to 2012.