Background: Previous study implicated that genes of matrix metalloproteinase (MMP) family play an important role in tumor invasion, neoangiogenesis, and metastasis. However, the diverse expression patterns and prognostic values of 24 MMPs in colorectal cancer are yet to be analyzed.Methods: In this study, by integrating public database and our data, we first investigated the expression levels and protein levels of MMPs in patients with colorectal cancer. Then, by using TCGA and GEO datasets, we evaluated the association of MMPs with clinicopathological parameters and prognosis of colorectal cancer. Finally, by using the cBioPortal online tool, we analyzed the alterations of MMPs and did the network and pathway analyses for MMPs and their nearby genes.Results: We found that, MMP1, MMP3, MMP7, MMP9–MMP12, and MMP14 were consistently upregulated in public dataset and our samples. Whereas, MMP28 was consistently downregulated in public dataset and our samples. In the clinicopathological analyses, upregulated MMP11, MMP14, MMP16, MMP17, MMP19, and MMP23B were significantly associated with a higher tumor stage. In the survival analyses, upregulated MMP11, MMP14, MMP17, and MMP19 were significantly associated with a shorter progression-free survival (PFS) time and a shorter relapse-free (RFS) time.Discussion: This study implied that MMP11, MMP14, MMP17, and MMP19 are potential targets of precision therapy for patients with colorectal cancer.

Summary: Background: To date, 14 single‐nucleotide polymorphisms (SNPs) have been identified as susceptibility loci for chronic hepatitis B (CHB).Aim: To investigate if these SNPs are associated with treatment response of hepatitis B e antigen (HBeAg)‐positive CHB patients.Methods: We performed a retrospective analysis of 1623 Han Chinese HBeAg‐positive CHB patients (782 patients treated with pegylated interferon alpha [PegIFNα] for 48 weeks plus 24 weeks follow‐up, and 841 patients treated with nucleos(t)ide analogues [NUCs] for 104 weeks) included in four phase‐IV multicentre randomised controlled trials. All 14 SNPs were genotyped for each CHB patient. A polygenic score (PGS) was used to evaluate the cumulative effect of multiple SNPs. The associations of SNPs or PGS with combined response (CR) and hepatitis B s antigen (HBsAg) loss were assessed.Results: We found that rs12614, a missense variant of complement factor B (CFB), was significantly associated with CR in PegIFNα‐treated patients, and the CR rate in patients with the rs12614 TT/CT genotype was less than one‐third of that in patients with the CC genotype (7.4% vs 22.6%, P = 0.009). Moreover, a PGS integrating CFB rs12614 and STAT4 rs7574865 (previously reported to be associated with response to PegIFNα) was significantly associated with both CR (P‐trend = 4.000 × 10⁻⁴) and HBsAg loss (P‐trend = 0.010) in PegIFNα‐treated patients. However, none of the SNPs were associated with treatment response in NUCs‐treated patients.Conclusions: CFB rs12614 is an independent predictor of response to PegIFNα therapy in Chinese HBeAg‐positive CHB patients. A PGS integrating CFB rs12614 with STAT4 rs7574865 can effectively discriminate responders to PegIFNα from nonresponders.

Export Background and Aims: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. Approach and Results: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 wk) or relapsers (relapsed patients who underwent NA re-treatment for up to 48 weeks and re-achieved stable viral control). HBV-specific T cell responses were detected at baseline and longitudinally throughout follow-up. We found responders had a greater magnitude of HBV Polymerase (Pol)-specific T cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core- and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short and long-term follow-up. Notably, CD4⁺T cells accounted for the predominance of HBV-specific T cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8⁺T cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4⁺T cells promoted HBsAb production by B cells . Additionally, interleukin (IL)-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4⁺T cell responses. Conclusion: HBV-specific CD4⁺T cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4⁺T cells specific for distinct HBV antigens may endow with divergent antiviral potential.