Gastric cancer (GC) is a prevalent malignancy in China, posing significant health challenges. The persistently high tumor incidence and the rising number of tumor survivors may elevate the risk of multiple primary malignancies (MPMs) in GC patients.

We conducted a retrospective study involving 11,045 patients diagnosed with gastric adenocarcinoma at National Cancer Center of China between 2010 and 2017. A 6‐month interval distinguished synchronous MPMs (SMPMs) from metachronous MPMs (MMPMs).

Of all GC patients, 443 (4.01%) had MPM, with 75.85% being males and an average age of 60 at initial diagnosis. Among the MPM cases, 415 (93.68%) had two primary cancers (53.98% synchronous and 46.02% metachronous), 27 (6.09%) had three, and 1 (0.23%) had four, totaling 472 extra gastric cancer sites. Esophageal, colorectal, and lung cancers were the most prevalent concomitant malignancies, with esophageal cancer more frequent in synchronous cases and breast cancer (observed only in females) more frequent in metachronous cases (both p < 0.001). In patients with two primary cancers, the SMPM subset included more males (p < 0.001), with higher rates of smoking (p = 0.012), alcohol consumption (p < 0.001), and higher T stage at first diagnosis (p < 0.001). The MMPM subset included more females (p < 0.001), was younger at first diagnosis (p < 0.001), and more frequently underwent surgery after first diagnosis (p < 0.001).

MPM occurring in patients with GC predominantly involve the esophagus, colorectum, and lung. Elderly male patients with smoking or alcohol use represent a higher‐risk group and warrant vigilant surveillance. This study provides a clinical and epidemiologic basis for future research on MPM in GC.

Pancreatic adenocarcinoma (PAAD) represents a highly fatal form of cancer. The 5‐year survival rate for patients with this disease is only around 10%. A significant hurdle in its management is the absence of characteristic early‐stage symptoms. As a result, a large majority of pancreatic cancer patients are diagnosed when the disease has reached an advanced stage or has metastasized. Consequently, taking measures to suppress the occurrence of metastasis in pancreatic cancer can bring about a substantial improvement in patients' survival rates and overall prognosis. SKIL, known to promote cancer progression, is implicated in cell proliferation, epithelial–mesenchymal transition (EMT), and metastasis, but its specific function in pancreatic cancer remains unclear.

We investigated the effects of SKIL on the proliferation, apoptosis, and metastasis of pancreatic cancer cells. Through ChIP‐seq, we identified the SKIL downstream target gene and further explored the mechanism by which SKIL regulates the metastasis of pancreatic cancer cells through functional experiments and Western blot.

A high level of SKIL expression is associated with an unfavorable prognosis in PAAD; it promotes cell migration and EMT. Through ChIP‐seq analysis, we identified that SKIL inhibits TSPYL2, a nuclear protein regulating the TGF‐β pathway by binding to the TGFB1 promoter. Further studies carried out by us confirmed that SKIL modulates the TGF‐β pathway via TSPYL2, facilitating EMT and metastasis in pancreatic cancer cells, independent of Smad4.

These findings reveal a novel regulatory mechanism involving SKIL, TSPYL2, and the TGF‐β pathway, offering new therapeutic targets for PAAD.

Immune checkpoint inhibitors have revolutionized cancer therapy for multiple types of solid tumors, but as expected, a large percentage of patients do not show durable responses. Biomarkers that can predict clinical responses to immunotherapies at diagnosis are therefore urgently needed. Herein, we determined the associations between baseline gut commensal microbes and the clinical treatment efficiencies of patients with thoracic neoplasms during anti-programmed death protein 1 (PD-1) therapy.

Forty-two patients with advanced thoracic carcinoma who received anti-PD-1 treatment were enrolled in the study. Baseline and time-serial stool samples were analyzed using 16S ribosomal RNA gene sequencing. Tumor responses, patient progression-free survival, and overall survival were used to measure clinical outcomes.

The diversities of the baseline gut microbiota were similar between responders (n = 23) and nonresponders (n = 19). The relative abundances of the Akkermansiaceae, Enterococcaceae, Enterobacteriaceae, Carnobacteriaceae and Clostridiales Family XI bacterial families were significantly higher in the responder group. These 5 bacterial families acted as a commensal consortium and better stratified patients according to clinical responses (P = 0.014). Patients with a higher abundance of commensal microbes had prolonged PFS (P = 0.00016). Using multivariable analysis, the abundance of the commensal consortium was identified as an independent predictor of anti-PD-1 immunotherapy in thoracic neoplasms (hazard ratio: 0.17; 95% confidence interval: 0.05–0.55; P = 0.003).

Baseline gut microbiota may have a critical impact on anti-PD-1 treatment in thoracic neoplasms. The abundance of gut commensal microbes at diagnosis might be useful for the early prediction of anti-PD-1 immunotherapy responses.