A portal cavernoma is defined as a network of veins, initially millimetric or even microscopic in size, that progressively dilates and through which hepatoportal blood continues to flow. It represents the body’s workaround for a problem: chronic occlusion of the extrahepatic portal system lasting more than three weeks. When the portal vein—the major vessel that channels nutrient-rich blood from the digestive organs to the liver—becomes irreversibly thrombosed, the surrounding tissue sprouts a tortuous meshwork of collateral channels to bypass the obstruction. First described in 1955 during the autopsy of a patient who died of mesenteric venous thrombosis, the condition has since become recognized as a significant cause of portal hypertension, but it remains sparsely documented in the African literature, particularly in sub-Saharan Africa, where only scattered case reports exist.

The patient’s initial presentation was deceptively ordinary. He had no particular medical history, yet he arrived with hematemesis—vomiting of blood—that had begun two days earlier, followed a day later by moderate diarrhea with blackish stools, a classic sign of digested blood passing through the gastrointestinal tract. There was no indication that he had consumed contaminated food or toxic substances. Clinical examination recorded a blood pressure of 100/60 mmHg, a heart rate elevated to 110 beats per minute, and a respiratory rate of 20 cycles per minute. His body mass index had fallen to 18 kg/m², signaling weight loss. Palpation revealed tenderness in the epigastric region, moderate ascites—fluid accumulating in the abdominal cavity—and an enlarged spleen consistent with Hackett stage II splenomegaly. Cardiac auscultation confirmed regular tachycardia at 110 beats per minute, a physiological compensation for volume loss.

Endoscopy performed shortly after admission revealed more than just the bulbar ulcer. The examination also identified grade IIa esophageal varices—dilated veins in the lining of the esophagus—without red signs, the endoscopic markers that predict imminent rupture. Additionally, the mucosa displayed a mosaic appearance, a hallmark of moderate portal hypertension. This combination should have raised a flag: peptic ulcers do not cause esophageal varices or mosaic mucosa, and both findings point toward elevated pressure in the portal venous system. Nevertheless, given the prominence of the ulcer and the positive H. pylori stool antigen test, the initial diagnosis of a bulbar ulcer was made, and eradication therapy was commenced. It was a reasonable start, but it addressed a contributor rather than the underlying engine of the disease.

The diagnostic turning point arrived two days later with an abdominal ultrasound. The study was consistent with heterogeneous portal vein thrombosis, accompanied by abundant ascites and, notably, a normal-sized, non-dysmorphic liver—an important observation, because cirrhosis is by far the most common cause of portal hypertension, and its absence demanded an alternative explanation. An abdominal computed tomography scan performed with portal vein injection then delivered the decisive findings. Contrast imaging revealed a heterogeneous filling defect in the portal trunk and its branches, with dilation of the vessels upstream of the obstruction, consistent with a thrombotic lesion of the portal trunk. The heterogeneous center of the lesion did not take up contrast, a pattern suggesting a portal cavernoma. The scan also demonstrated thrombosis of the splenic vein, a splenic nodule suggestive of an angioma, and an atrophic pancreas with a 9-millimeter dilation of the Wirsung duct, the main pancreatic duct.

Laboratory workup added nuance rather than contradiction. Transaminases were only slightly elevated, with AST at 44 IU/L and ALT at 48 IU/L, while the blood ionogram, complete blood count, and prothrombin level were all normal. Serology for HIV, hepatitis B, and hepatitis C came back negative, ruling out the viral infections that account for much of chronic liver disease worldwide. The etiological investigation, however, hit a practical wall: thrombophilia testing—including assays for protein C and S, antithrombin III, factor V Leiden, and the JAK2 mutation—could not be performed because these tests were simply unavailable in the clinical setting. This gap matters, because in adults the onset of portal vein thrombosis most often results from a combination of local and systemic prothrombotic factors, and guidelines call for systematic investigation of underlying thrombophilic disease.

With the imaging and clinical picture aligned, the team made their diagnosis: portal cavernoma revealed by gastrointestinal hemorrhage. The mechanism is elegant yet perilous. The portal obstruction creates a network of collateral veins of varying caliber through which hepatoportal blood is rerouted, but these fragile channels—and the varices they feed—operate under elevated pressure. In this patient, the hemorrhage was driven by rupture-prone esophageal varices, which occur in 90 to 95 percent of portal cavernoma cases, making variceal bleeding both the most common mode of presentation and the most feared complication. Other manifestations, including splenomegaly, abdominal pain, ascites, and transit disorders such as the patient’s diarrhea, are frequent but neither constant nor specific. The authors also point to portal hypertensive enteropathy and pancreatic atrophy as contributors to exocrine pancreatic insufficiency, which produces mucosal congestion, malabsorption, and diarrhea—a chain of physiological consequences that links seemingly unrelated symptoms back to the obstructed portal vein.

Treatment proceeded on several fronts simultaneously. The patient received 40 mg of injectable omeprazole every 12 hours to suppress acid and protect the ulcer, 40 mg of propranolol per day—a nonselective beta blocker that lowers portal pressure and provides primary or secondary prevention of variceal hemorrhage—and one sachet of Gaviscon every 8 hours. Endoscopic band ligation was performed to control the bleeding varices directly, and once hemorrhage was arrested, anticoagulation was initiated with 0.8 mL of enoxaparin every 12 hours, later transitioned to 4 mg of acenocoumarol daily with a target International Normalized Ratio of 2 to 3. Anticoagulation in portal cavernoma aims to prevent extension of thrombosis and, in some cases, to allow recanalization, though it must be balanced against the risk of rebleeding from varices.

The clinical evolution was favorable. Abdominal pain, ascites, and gastrointestinal bleeding all regressed, and the patient was discharged home after 10 days, following two stable INR readings of 2.3 and 2.5. Remarkably, no blood transfusion was required, as he remained hemodynamically stable with a hemoglobin level of 11 g/dL. He left the hospital on 40 mg of oral omeprazole twice daily and 4 mg of acenocoumarol, with anticoagulation planned for six months. At a three-month follow-up visit, he showed complete resolution of symptoms with a stable INR. Unfortunately, at the six-month mark the patient was lost to follow-up, and the team was unable to obtain follow-up imaging to assess whether the cavernoma had evolved, a sobering reminder of the practical challenges of longitudinal care in resource-limited settings.

The epidemiological context underscores just how unusual this case is. In the United States, the incidence of portal cavernoma is estimated at about 1 percent of the general population, based on large autopsy studies that documented portal vein thrombosis prevalence and lifetime risk across more than 23,000 consecutive examinations. In Africa, the true incidence is unknown but is thought to be below 1 percent according to the available literature. A Tunisian study in 2001 described just 19 observations over 25 years, while a Moroccan series reported 11 cases between 2003 and 2012. Most series show a male predominance, and the condition is overwhelmingly described in pediatric populations, where omphalitis—infection of the umbilical stump—remains a common cause of portal thrombosis in developing countries. In children, portal vein obstruction is also associated with growth retardation, attributed to reduced hepatoportal flow and resistance to growth hormone. Adult presentations in middle age, such as this one, are exceptionally rare in the published record.

The therapeutic hierarchy for portal cavernoma extends well beyond the medical management available to this patient. Beta blockers remain the cornerstone of hemorrhage prevention, but when endoscopic and pharmacological measures fail, ligation or sclerotherapy of varices is indicated, and in cases complicated by biliary symptoms—cavernomas can compress the bile ducts, producing a condition known as portal biliopathy—a porto-systemic shunt, with or without a porto-biliary shunt, may be required. Such surgical options demand infrastructure and expertise that are often unavailable in the settings where the disease is most likely to go undiagnosed. For the authors of this report, the case is a call to vigilance: when a patient presents with gastrointestinal hemorrhage and the endoscopy shows findings that exceed the usual scope of peptic ulcer disease, clinicians must look deeper into the portal vasculature. The ulcer, in this story, was real—but it was the supporting actor, not the star.

The pathogenesis of gastric cancer typically unfolds through a chronic continuum of histopathological changes, beginning with superficial gastritis and gradually advancing to chronic atrophic gastritis, intestinal metaplasia, dysplasia, and eventually adenocarcinoma. Central to this cascade is infection by H. pylori, a bacterium implicated in nearly 90% of non-cardia gastric cancer cases. Historically, therapeutic eradication of H. pylori infection has been the cornerstone for reducing gastric cancer risk, yet the precise molecular events bridging bacterial colonization to neoplastic transformation remained inadequately characterized. Prior investigations tended to isolate singular pathways such as inflammation or immune dysfunction without providing an integrated molecular landscape of disease evolution.

Addressing this significant gap, researchers from Peking University Cancer Hospital & Institute and affiliated collaborators launched a multi-dimensional study integrating high-throughput proteomics and single-cell transcriptomics across a broad spectrum of gastric tissue samples. Published in September 2025 in Cancer Biology & Medicine, the study analyzed 166 gastric tissue specimens from Linqu, a Chinese region with a high incidence of gastric cancer, alongside 99 additional samples from Beijing patients. Over 4,200 proteins were quantitatively profiled, marking one of the most expansive proteomic inquiries into gastric carcinogenesis to date.

From this expansive dataset, 28 protein markers emerged as pivotal players closely associated with H. pylori infection and the malignant transformation of gastric tissue. Notably, proteins such as OLFM4 (olfactomedin 4) and ENO1 (enolase 1) exhibited marked upregulation, while others including GSN (gelsolin) and IGFBP2 (insulin-like growth factor-binding protein 2) were found to be downregulated. Crucially, these protein alterations were not random but followed a consistent pattern correlating with successive stages of gastric lesion progression, underscoring their fundamental role in carcinogenic processes.

To decipher cellular heterogeneity underpinning these proteomic shifts, the team employed single-cell RNA sequencing on approximately 135,000 gastric epithelial and stromal cells spanning disease stages from normal mucosa to intestinal metaplasia and cancer cells. This transcriptomic analysis revealed stage-specific gene expression dynamics for the protein-encoding genes, linking molecular changes at the single-cell resolution to macroscopic lesion development. Such integrative omics approaches bolster confidence that these protein signatures reflect true biological drivers rather than superficial epiphenomena.

Recognizing the potential clinical impact, the researchers constructed tissue-based and circulating protein panels to stratify patients according to their gastric cancer risk. The tissue panel incorporated 15 proteins whose expression profiles could categorize patients into risk quartiles, with the highest quartile exhibiting an over sevenfold increased odds of neoplastic progression compared to the lowest quartile. This powerful stratification tool offers a foundation for personalized surveillance and management protocols, enabling clinicians to prioritize high-risk individuals for closer monitoring or interventional therapies.

Extending the relevance of their findings to population-scale contexts, the investigators validated a four-protein circulating blood panel comprising OLFM4, ENO1, GSN, and IGFBP2 using plasma samples from the UK Biobank cohort, which includes 48,529 participants. Individuals identified as high risk via this circulating panel were nearly four times more likely to develop gastric cancer over follow-up compared to those in the lowest risk group. This non-invasive biomarker panel presents a compelling opportunity to revolutionize gastric cancer screening by facilitating broad, population-level risk stratification without the burdens associated with endoscopic procedures.

The implications of this research are profound, as it not only elucidates previously unclear molecular pathways connecting H. pylori infection to gastric carcinogenesis but also lays the groundwork for impactful clinical translatability. Integrating proteomic biomarkers with single-cell transcriptomics and longitudinal follow-up, the study delivers a comprehensive molecular narrative of disease progression. This paves the way for novel prevention strategies aimed at intercepting gastric cancer at its earliest, most curable stages.

Dr. Wenqing Li, the senior author, emphasized the transformative potential of these findings: “By mapping the proteomic and transcriptomic changes throughout gastric lesion development, we have unveiled consistent protein markers that illuminate the biology of H. pylori-induced carcinogenesis. These biomarkers are poised to become invaluable tools for risk stratification, enabling targeted surveillance and early intervention in high-risk populations.” Such precision medicine approaches are urgently needed to overcome current screening limitations, especially in resource-constrained settings where endoscopy access is limited.

From a public health perspective, the development of blood-based biomarker panels could democratize gastric cancer prevention, offering a minimally invasive, cost-effective means to identify individuals needing further diagnostic assessment. This contrasts with current endoscopic screening strategies that, while effective, are invasive, expensive, and challenging to implement at scale. Consequently, widespread adoption of validated circulating biomarkers has the potential to significantly reduce gastric cancer incidence and mortality worldwide.

Beyond clinical screening, the identified protein signatures provide a valuable framework for future therapeutic exploration. Characterizing how these proteins function in mediating infection-driven tissue remodeling and neoplastic transformation may uncover novel drug targets capable of disrupting the carcinogenic process. Interventions aimed at modulating these molecular pathways could complement existing eradication therapies and immunomodulatory strategies, leading to integrated multi-modal prevention regimens.

In conclusion, this comprehensive proteomic and transcriptomic study represents a paradigm shift in understanding the molecular genesis of gastric cancer from H. pylori infection. By delineating a reproducible trajectory of protein alterations across tissue and circulation, it offers groundbreaking tools for early diagnosis, risk stratification, and personalized prevention. As these biomarkers advance through prospective validation and clinical translation phases, they hold promise to substantially diminish the global burden of gastric cancer through earlier detection and targeted intervention.

Subject of Research:
Gastric cancer, Helicobacter pylori infection, proteomic profiling, single-cell RNA sequencing, molecular biomarkers, gastric lesion progression

Article Title:
Proteomic profiling and scRNA sequencing identify signatures associated with Helicobacter pylori infection and risk of developing gastric cancer

News Publication Date:
September 4, 2025

Web References:
https://www.cancerbiomed.org/content/22/8/946

References:
DOI: 10.20892/j.issn.2095-3941.2025.0077

Image Credits:
Cancer Biology & Medicine

Keywords:
Gastric cancer, Helicobacter pylori, proteomics, single-cell RNA sequencing, biomarker panels, gastric lesions, cancer progression, early detection, risk stratification, molecular signatures