Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer.

BACKGROUND: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored. METHODS: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. RESULTS: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment. CONCLUSIONS: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.

Locally advanced cervical rhabdomyosarcoma in adults: A case report.

BACKGROUND: Rhabdomyosarcoma is a soft tissue tumor of primitive mesenchymal cells origin, occurring predominantly in children and adolescents, but extremely rare in adults and the data regarding its treatment are sparse. Here, we would like to share our experience in the treatment of a locally advanced primary embryonal rhabdomyosarcoma of cervix in a 39-year-old female. CASE SUMMARY: The patient was admitted with symptoms of intermenstrual bleeding and postcoital bleeding for six months. Physical examination revealed a friable, polyp-like mass (5 cm × 5 cm) in her cervix protruding into the vagina, while the uterus was mobile and normal-sized. Colposcopy-directed biopsy was performed, and a pathological diagnosis of embryonal rhabdomyosarcoma was made. Magnetic resonance imaging of the pelvis showed that the cervical volume was significantly increased, with a hypointense and hyperintense soft tissue mass on the right side, invading the cervical stroma; the mass was 5 cm × 5 cm with a clear boundary and confined to the cervix; there were no obvious findings indicating tumor invasion in the vaginal wall, parametrium, or pelvic wall; no enlarged lymph nodes were observed in the pelvic cavity. Based on our findings, the tumor was classified as stage IA according to the intergroup rhabdomyosarcoma studies criteria and IB3 stage according to The International Federation of Gynecology and Obstetrics 2018. The patient underwent two courses of neoadjuvant chemotherapy and a partial remission was achieved. Subsequently, she underwent laparoscopic radical hysterectomy, bilateral salpingo-oophrectomy and pelvic lymph node dissection and there were no risk factors revealed by postoperative pathological examination. Adjuvant chemotherapy was performed after surgery. The patient was disease-free until the last follow-up, 49 mo after completing the entire treatment. CONCLUSION: Our experience suggests that neoadjuvant vincristine, dactinomycin, and cyclophosphamide chemotherapy followed by radical surgery and adjuvant chemotherapy might be reasonable therapeutic option for bulky cervical rhabdomyosarcoma in adults without fertility desire. Since large-scale studies on such rare conditions are rather impossible, further case reports and systematic reviews could help optimize the treatment of primary, bulky cervical rhabdomyosarcoma in adults.