The strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) is involved in cell migration, motility and invasion. The object of this study is to investigate the involvement of CTHRC1 in NSCLC invasion and metastasis. A proteomic analysis was performed to identify the different expression proteins between NSCLC and normal tissues. Cell lines stably express CTHRC1, MMP7, MMP9 were established. Invasion and migration were determined by scratch and transwell assays respectively. Clinical correlations of CTHRC1 in a cohort of 230 NSCLC patients were analysed. CTHRC1 is overexpressed in NSCLC as measured by proteomic analysis. Additionally, CTHRC1 increases tumour cell migration and invasion in vitro. Furthermore, CTHRC1 expression is significantly correlated with matrix metalloproteinase (MMP)7 and MMP9 expression in sera and tumour tissues from NSCLC. The invasion ability mediated by CTHRC1 were mainly MMP7- and MMP9-dependent. MMP7 or MMP9 depletion significantly eradicated the pro-invasive effects mediated by CTHRC1 on NSCLC cells. Clinically, patients with high CTHRC1 expression had poor survival. CTHRC1 serves as a pro-metastatic gene that contributes to NSCLC invasion and metastasis, which are mediated by upregulated MMP7 and MMP9 expression. Targeting CTHRC1 may be beneficial for inhibiting NSCLC metastasis.

Backgrounds: Colorectal cancer is the third most prevalent cancer worldwide. A right-sided colon cancer patient typically has a worse prognosis than one who has a left-sided colon cancer. There is an unclear understanding of how left-sided colon cancer differs from right-sided colon cancer in tumor-infiltrating immune cells (TIICs) and relevant genes. Methods: The Cancer Genome Atlas provided RNA-seq data and clinical information regarding colon adenocarcinoma. We conducted a single-sample gene set enrichment analysis (ssGSEA) to quantify the level of 24 immune cells infiltrating the tissues. Based on an analysis of univariate Cox regression, immune cell types associated with survival were identified. Weighted gene co-expression network analysis (WGCNA) was used to identify hub genes related to location and critical immune cells. Based on the Search Tool for the Retrieval of Interacting Genes (STRING), interaction potential was predicted among the hub genes. Hub genes that influence outcomes through immune infiltration were identified using the least absolute shrinkage and selection operator (LASSO). Then, we used the TISIDB database (a repository portal for tumor–immune system interactions) to validate the correlation between hub genes and immune cell infiltration. Finally, immunohistochemical assays were conducted to determine the levels of proteins expressed by critical TIICs and cancer cells. Results: Colon cancers on the right side of the body had higher levels of myeloid-derived suppressor cells (MDSCs) than on the left side. There were three key genes: LCP1, ITGB2, and IKZF1. It was found that their expression was linked to poor prognosis and an increased level of MDSC infiltration. An immunohistochemical study confirmed these findings. Conclusions: There is a higher rate of MDSC infiltration in right-sided colon cancer when compared with left-sided colon cancer. COAD outcomes are associated with changes in MDSC infiltration, and therefore LCP1, ITGB2, and IKZF1 may be novel targets for immunotherapy.

Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. We developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro. NanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p < 0.05). Further, Correlation between CTC counts and pTNM stage determined by NanoVelcro was more significant than that determined by CellSearch (p < 0.001 VS p = 0.029). All ALK-positive patients had 3 or more ALK-rearranged CTC per ml of blood. Less than 3 ALK-rearranged CTC was detected in ALK-negative patients. NanoVelcro can detect the ALK–rearranged status with consistent sensitivity and specificity compared to biopsy test. Furthermore, the ALK-rearranged CTC ratio correlated to the pTNM stage in ALK-positive patients. Following up showed that CTCs counting by NanoVelcro was more stable and reliable in evaluating the efficacy of Clozotinib both in the short and long run compared with CellSearch. Changing of NanoVlecro CTC counts could accurately reflect disease progression. NanoVelcro provides a sensitive method for CTC counts and characterization in advanced NSCLC. ALK-rearrangement can be detected in CTCs collected from advanced NSCLC patients by NanoVelcro, facilitating diagnostic test and prognosis analysis, most importantly offering one noninvasive method for real-time monitoring of treatment reaction.

Lung adenocarcinoma (LUAD) remains one of the leading causes of death in patients with cancer. The association of CD155 with CD96 transmits an inhibitory signal and suppresses antitumor immune response. This study investigates the effect of CD155/CD96 on immune suppression in LUAD. We demonstrate that LUAD patients with high CD155 expression suffer from immune suppression and experience a poor prognosis, which coincides with an inhibited AKT-mTOR signaling pathway in CD8 T cells and subsequently up-regulated CD96 expression. Moreover, the inhibition effect can be reversed by CD96 blocking antibody. High CD155 expression inhibited the release of IFNγ from CD8 cells. Moreover, Blocking CD96 restored IFNγ production in CD8 T cells and neutralized the inhibition of IFNγ production in CD8 T cells mediated by CD155. Animal experiments showed that CD155-mediated LUAD growth might depend on its suppression antitumor immune response in the tumor microenvironment in PDX mice. In conclusion, our results suggest that LUAD cells suppress antitumor immune response in the tumor microenvironment through CD155/CD96. CD155/CD96 could be a potential therapeutic target for LUAD patients. Abbreviations: LUAD: lung adenocarcinoma; IFNγ: interferon gamma; PDX: patient-derived xenograft; NSCLC: non-small cell lung cancer; PRR: poliovirus receptor–related; MDSCs: myeloid-derived suppressor cells; PRR: poliovirus receptor–related; STR: short tandem repeat; IRS: immunoreactive score; SI: staining intensity; PP: percentage of positive cells; RT-PCR: reverse transcription-polymerase chain reaction; PBS: phosphate-buffered saline; PBMCs: peripheral blood mononuclear cells; SDS–PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; rCD155: recombinant human CD155; LUAD cells: lung adenocarcinoma cells; TILs: tumor-infiltrating lymphocytes; GzmB: granzyme B; IL-2 (Interleukin-2); TNF-α : tumor necrosis factor-alpha; PI: propidium Iodide; PDX: patient-derived xenograft; TIGIT: T cell immunoreceptor with Igand ITIM domains; WBC: white blood cells; MFI: mean fluorescence intensity; HPF: high power field