Spatial transcriptomic analysis reveals local effects of intratumoral fusobacterial infection on DNA damage and immune signaling in rectal cancer.

Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC. The objective of this study was therefore to increase our understanding of beneficial and detrimental effects of fusobacterial infection, by contrasting host cell signaling and immune responses in areas of high vs. low infection, using mucinous rectal cancer as a clinically relevant example. We employed spatial transcriptomic profiling of 106 regions of interest from 8 mucinous rectal cancer samples to study gene expression in the epithelial and immune segments across regions of high versus low fusobacterial infection. Fusobacteria high regions were associated with increased oxidative stress, DNA damage, and P53 signaling. Meanwhile regions of low fusobacterial prevalence were characterized by elevated JAK-STAT, Il-17, Il-1, chemokine and TNF signaling. Immune masks within fusobacterial high regions were characterized by elevated proportions of cytotoxic (CD8+) T cells (p = 0.037), natural killer (NK) cells (p < 0.001), B-cells (p < 0.001), and gamma delta T cells (p = 0.003). Meanwhile, fusobacteria low regions were associated with significantly greater M2 macrophage (p < 0.001), fibroblast (p < 0.001), pericyte (p = 0.002), and endothelial (p < 0.001) counts.

Meta-analysis of SATB2 immunohistochemical expression in colorectal cancer versus primary ovarian mucinous neoplasms.

BACKGROUND: Reliably distinguishing primary ovarian mucinous neoplasms (POMNs) from metastatic colorectal cancers (CRCs) is both challenging to the histopathologist and of great clinical importance. Special AT-rich sequence binding protein-2 (SATB2) has emerged as a useful diagnostic immunohistochemical marker of colorectal cancer. This meta-analysis compares SATB2 expression in POMNs and CRC. METHODS: A systematic literature search for relevant studies was conducted. Meta-analysis of SATB2 positivity was undertaken using a random effects model. RESULTS: Seven studies including 711 CRCs and 528 POMNs were included. SATB2 positivity was seen in 81 % (95 % CI: 72-88 %) of CRCs and 4 % (95 % CI: 1-11 %) of POMNs. Variation was seen in immunohistochemical methods used for SATB2 detection and threshold for positivity. CONCLUSION: SATB2 staining remains high in CRC and low in POMNs, supporting its use in differentiating these two pathologies with vastly differing prognosis and treatment.

Quality of life meta-analysis following coloanal anastomosis versus abdominoperineal resection for low rectal cancer.

AIM: In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer. METHODS: Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p < 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea. DISCUSSION: It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.